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訪問者数 1270      最終更新 2010-03-24 (水) 12:02:48

Stanford Parserを使ってみる

PubMedで ( "Colorectal cancer" aspirin ) で検索。最新10編の論文のアブストラクトをStanford Parserで文法解析してみる。

その1

1: Biochem Biophys Res Commun. 2009 Sep 26.

Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention.

Chen W, Zhu H, Jia Z, Li J, Misra HP, Zhou K, Li Y.

Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060, USA; College of Food Science and Biological Engineering, Zhejiang Gongshang University, Hangzhou 310035, China; Department of Food Science and Technology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in phiX-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250muM SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

PMID: 19785994 [PubMed - as supplied by publisher]

(ROOT
  (S
    (NP (JJ Epidemiological) (NNS studies))
    (VP (VBP have)
      (VP (VBN suggested)
        (SBAR (IN that)
          (S
            (NP
              (NP (DT the) (JJ long-term) (NN use))
              (PP (IN of)
                (NP (NN aspirin))))
            (VP (VBZ is)
              (VP (VBN associated)
                (PP (IN with)
                  (NP
                    (NP (DT a) (VBN decreased) (NN incidence))
                    (PP (IN of)
                      (NP
                        (NP (JJ human) (NNS malignancies))
                        (, ,)
                        (NP
                          (ADJP (RB especially) (JJ colorectal))
                          (NN cancer))))))))))))
    (. .)))

amod(studies-2, Epidemiological-1)
nsubj(suggested-4, studies-2)
aux(suggested-4, have-3)
complm(associated-12, that-5)
det(use-8, the-6)
amod(use-8, long-term-7)
nsubjpass(associated-12, use-8)
prep_of(use-8, aspirin-10)
auxpass(associated-12, is-11)
ccomp(suggested-4, associated-12)
det(incidence-16, a-14)
amod(incidence-16, decreased-15)
prep_with(associated-12, incidence-16)
amod(malignancies-19, human-18)
prep_of(incidence-16, malignancies-19)
advmod(colorectal-22, especially-21)
amod(cancer-23, colorectal-22)
appos(malignancies-19, cancer-23)
(ROOT
  (S
    (SBAR (IN Since)
      (S
        (S
          (VP (VBG accumulating)
            (NP (NN evidence))))
        (VP (VBZ indicates)
          (SBAR (IN that)
            (S
              (NP (NN peroxynitrite))
              (VP (VBZ is)
                (ADJP (RB critically) (VBN involved)
                  (PP (IN in)
                    (NP (JJ multistage) (NNS carcinogenesis))))))))))
    (, ,)
    (NP (DT this) (NN study))
    (VP (VBD was)
      (VP (VBN undertaken)
        (S
          (VP (TO to)
            (VP (VB investigate)
              (NP
                (NP (DT the) (NN ability))
                (PP (IN of)
                  (NP (NN aspirin))))
              (S
                (VP (TO to)
                  (VP (VB inhibit)
                    (NP (JJ peroxynitrite-mediated) (NN DNA) (NN damage))))))))))
    (. .)))

mark(indicates-4, Since-1)
csubj(indicates-4, accumulating-2)
dobj(accumulating-2, evidence-3)
advcl(undertaken-17, indicates-4)
complm(involved-9, that-5)
nsubjpass(involved-9, peroxynitrite-6)
auxpass(involved-9, is-7)
advmod(involved-9, critically-8)
ccomp(indicates-4, involved-9)
amod(carcinogenesis-12, multistage-11)
prep_in(involved-9, carcinogenesis-12)
det(study-15, this-14)
nsubjpass(undertaken-17, study-15)
auxpass(undertaken-17, was-16)
aux(investigate-19, to-18)
xcomp(undertaken-17, investigate-19)
det(ability-21, the-20)
dobj(investigate-19, ability-21)
prep_of(ability-21, aspirin-23)
aux(inhibit-25, to-24)
xcomp(investigate-19, inhibit-25)
amod(damage-28, peroxynitrite-mediated-26)
nn(damage-28, DNA-27)
dobj(inhibit-25, damage-28)
(ROOT
  (S
    (NP
      (NP (NNP Peroxynitrite))
      (CC and)
      (NP
        (NP (PRP$ its) (NN generator) (NN 3-morpholinosydnonimine))
        (PRN (-LRB- -LRB-)
          (NP (NN SIN-1))
          (-RRB- -RRB-))))
    (VP (VBD were)
      (VP (VBN used)
        (S
          (VP (TO to)
            (VP (VB cause)
              (NP
                (NP (NN DNA) (VBN strand) (NNS breaks))
                (PP (IN in)
                  (NP (JJ phiX-174) (JJ plasmid) (NN DNA)))))))))
    (. .)))

nsubjpass(used-10, Peroxynitrite-1)
poss(3-morpholinosydnonimine-5, its-3)
nn(3-morpholinosydnonimine-5, generator-4)
conj_and(Peroxynitrite-1, 3-morpholinosydnonimine-5)
appos(3-morpholinosydnonimine-5, SIN-1-7)
auxpass(used-10, were-9)
aux(cause-12, to-11)
xcomp(used-10, cause-12)
nn(breaks-15, DNA-13)
amod(breaks-15, strand-14)
dobj(cause-12, breaks-15)
amod(DNA-19, phiX-174-17)
amod(DNA-19, plasmid-18)
prep_in(breaks-15, DNA-19)
(ROOT
  (S
    (NP (PRP We))
    (VP (VBD demonstrated)
      (SBAR (IN that)
        (S
          (NP
            (NP (DT the) (NN presence))
            (PP (IN of)
              (NP
                (NP (NN aspirin))
                (PP (IN at)
                  (NP
                    (NP
                      (NP (NNS concentrations))
                      (PRN (-LRB- -LRB-)
                        (NP (NN 0.25-2mM))
                        (-RRB- -RRB-)))
                    (ADJP (JJ compatible)
                      (PP (IN with)
                        (NP
                          (NP (NNS amounts))
                          (PP (IN in)
                            (NP
                              (NP (NN plasma))
                              (PP (IN during)
                                (NP (JJ chronic) (JJ anti-inflammatory) (NN therapy)))))))))))))
          (VP (VBD resulted)
            (PP (IN in)
              (NP
                (NP (DT a) (JJ significant) (NN inhibition))
                (PP (IN of)
                  (NP
                    (NP (NN DNA) (NN cleavage))
                    (VP (VBN induced)
                      (PP (IN by)
                        (NP (DT both) (NN peroxynitrite)
                          (CC and)
                          (NN SIN-1))))))))))))
    (. .)))

nsubj(demonstrated-2, We-1)
complm(resulted-22, that-3)
det(presence-5, the-4)
nsubj(resulted-22, presence-5)
prep_of(presence-5, aspirin-7)
prep_at(aspirin-7, concentrations-9)
appos(concentrations-9, 0.25-2mM-11)
amod(concentrations-9, compatible-13)
prep_with(compatible-13, amounts-15)
prep_in(amounts-15, plasma-17)
amod(therapy-21, chronic-19)
amod(therapy-21, anti-inflammatory-20)
prep_during(plasma-17, therapy-21)
ccomp(demonstrated-2, resulted-22)
det(inhibition-26, a-24)
amod(inhibition-26, significant-25)
prep_in(resulted-22, inhibition-26)
nn(cleavage-29, DNA-28)
prep_of(inhibition-26, cleavage-29)
partmod(cleavage-29, induced-30)
preconj(peroxynitrite-33, both-32)
agent(induced-30, peroxynitrite-33)
conj_and(peroxynitrite-33, SIN-1-35)
(ROOT
  (S
    (ADVP (RB Moreover))
    (, ,)
    (NP
      (NP (DT the) (NN consumption))
      (PP (IN of)
        (NP
          (NP (NN oxygen))
          (VP (VBN caused)
            (PP (IN by)
              (NP (JJ 250muM) (NN SIN-1)))))))
    (VP (VBD was)
      (VP (VBN found)
        (S
          (VP (TO to)
            (VP (VB be)
              (VP (VBN decreased)
                (PP (IN in)
                  (NP
                    (NP (DT the) (NN presence))
                    (PP (IN of)
                      (NP (NN aspirin)))))))))
        (, ,)
        (S
          (VP (VBG indicating)
            (SBAR (IN that)
              (S
                (NP (NN aspirin))
                (VP (MD might)
                  (VP (VB affect)
                    (NP
                      (NP (DT the) (NN auto-oxidation))
                      (PP (IN of)
                        (NP (NN SIN-1))))))))))))
    (. .)))

advmod(found-12, Moreover-1)
det(consumption-4, the-3)
nsubjpass(found-12, consumption-4)
prep_of(consumption-4, oxygen-6)
partmod(oxygen-6, caused-7)
amod(SIN-1-10, 250muM-9)
agent(caused-7, SIN-1-10)
auxpass(found-12, was-11)
aux(decreased-15, to-13)
auxpass(decreased-15, be-14)
xcomp(found-12, decreased-15)
det(presence-18, the-17)
prep_in(decreased-15, presence-18)
prep_of(presence-18, aspirin-20)
xcomp(found-12, indicating-22)
complm(affect-26, that-23)
nsubj(affect-26, aspirin-24)
aux(affect-26, might-25)
ccomp(indicating-22, affect-26)
det(auto-oxidation-28, the-27)
dobj(affect-26, auto-oxidation-28)
prep_of(auto-oxidation-28, SIN-1-30)
(ROOT
  (S
    (ADVP (RB Furthermore))
    (, ,)
    (S
      (NP
        (NP (NNP EPR))
        (VP
          (ADVP (RB spectroscopy))
          (VBG using)
          (NP
            (NP
              (NP (NN 5,5-dimethylpyrroline-N-oxide))
              (PRN (-LRB- -LRB-)
                (NP (NNP DMPO))
                (-RRB- -RRB-)))
            (PP (IN as)
              (NP (DT a) (NN spin) (NN trap))))))
      (VP (VBD demonstrated)
        (NP
          (NP (DT the) (NN formation))
          (PP (IN of)
            (NP
              (NP (JJ DMPO-hydroxyl) (JJ radical) (NN adduct))
              (PRN (-LRB- -LRB-)
                (NP (NNP DMPO-OH))
                (-RRB- -RRB-)))))
        (PP (IN from)
          (NP (JJ authentic) (NN peroxynitrite)))))
    (, ,)
    (CC and)
    (S
      (NP
        (NP (DT that) (NN aspirin))
        (PP (IN at)
           (NP (JJ 0.25-2mM) (NNS potently))))
      (VP (VBD diminished)
        (NP (DT the) (JJ radical) (NN adduct) (NN formation))
        (PP (IN in)
          (NP (DT a) (JJ concentration-dependent) (NN manner)))))
    (. .)))

advmod(demonstrated-14, Furthermore-1)
nsubj(demonstrated-14, EPR-3)
advmod(using-5, spectroscopy-4)
partmod(EPR-3, using-5)
dobj(using-5, 5,5-dimethylpyrroline-N-oxide-6)
abbrev(5,5-dimethylpyrroline-N-oxide-6, DMPO-8)
det(trap-13, a-11)
nn(trap-13, spin-12)
prep_as(5,5-dimethylpyrroline-N-oxide-6, trap-13)
det(formation-16, the-15)
dobj(demonstrated-14, formation-16)
amod(adduct-20, DMPO-hydroxyl-18)
amod(adduct-20, radical-19)
prep_of(formation-16, adduct-20)
abbrev(adduct-20, DMPO-OH-22)
amod(peroxynitrite-26, authentic-25)
prep_from(demonstrated-14, peroxynitrite-26)
det(aspirin-30, that-29)
nsubj(diminished-34, aspirin-30)
amod(potently-33, 0.25-2mM-32)
prep_at(aspirin-30, potently-33)
conj_and(demonstrated-14, diminished-34)
det(formation-38, the-35)
amod(formation-38, radical-36)
nn(formation-38, adduct-37)
dobj(diminished-34, formation-38)
det(manner-42, a-40)
amod(manner-42, concentration-dependent-41)
prep_in(diminished-34, manner-42)
(ROOT
  (S
    (S
      (VP (VBN Taken)
        (ADVP (RB together))))
    (, ,)
    (NP (DT these) (NNS results))
    (VP (VBP demonstrate)
      (PP (IN for)
        (NP (DT the) (JJ first) (NN time)))
      (SBAR (IN that)
        (S
          (NP
            (NP (NN aspirin))
            (PP (IN at)
              (NP
                (ADJP (RB pharmacologically) (JJ relevant))
                (NNS concentrations))))
          (VP (MD can)
            (VP (VB inhibit)
              (NP
                (NP (JJ peroxynitrite-mediated) (NN DNA) (NN strand) (NN breakage))
                (CC and)
                (NP (NN hydroxyl) (JJ radical) (NN formation))))))))
    (. .)))

ccomp(demonstrate-6, Taken-1)
advmod(Taken-1, together-2)
det(results-5, these-4)
nsubj(demonstrate-6, results-5)
det(time-10, the-8)
amod(time-10, first-9)
prep_for(demonstrate-6, time-10)
complm(inhibit-18, that-11)
nsubj(inhibit-18, aspirin-12)
advmod(relevant-15, pharmacologically-14)
amod(concentrations-16, relevant-15)
prep_at(aspirin-12, concentrations-16)
aux(inhibit-18, can-17)
ccomp(demonstrate-6, inhibit-18)
amod(breakage-22, peroxynitrite-mediated-19)
nn(breakage-22, DNA-20)
nn(breakage-22, strand-21)
dobj(inhibit-18, breakage-22)
nn(formation-26, hydroxyl-24)
amod(formation-26, radical-25)
conj_and(breakage-22, formation-26)
(ROOT
  (S
    (NP (DT These) (NNS results))
    (VP (MD may)
      (VP (VB have)
        (NP
          (NP (NNS implications))
          (PP (IN for)
            (NP (NN cancer) (NN intervention))))
        (PP (IN by)
          (NP (NN aspirin)))))
    (. .)))

det(results-2, These-1)
nsubj(have-4, results-2)
aux(have-4, may-3)
dobj(have-4, implications-5)
nn(intervention-8, cancer-7)
prep_for(implications-5, intervention-8)
prep_by(have-4, aspirin-10)

fileちょっと見に気が付いたこと

その2

1: Curr Gastroenterol Rep. 2009 Oct;11(5):345-53.

NSAIDs and the gastrointestinal tract.

Gupta M, Eisen GM.

Division of Gastroenterology, Digestive Health Center, Center for Health and Healing, 6th Floor, Oregon Health and Science University, Portland, OR 97239, USA.

NSAIDs incur significant gastrointestinal (GI) side effects. The complication risk increases with history of peptic ulcer or older age. Helicobacter pylori infection and cardioprotective aspirin have independent and additive risks in the presence of NSAID use. NSAID enteropathy is increasingly recognized. Cardiovascular and GI risk stratification and H. pylori infection testing should be done before initiating NSAIDs. An NSAID combined with a proton pump inhibitor (PPI) is comparable to cyclooxygenase (COX)-2 inhibitors for gastroprotection, but for high-risk patients, COX-2 plus PPI should be considered. Aspirin and COX-2 inhibitors are associated with reduced colon adenoma risk, but higher dose and longer duration of treatment with aspirin appears effective. Hence, patients at high risk of colorectal cancer (with significant family or personal history of premalignant adenoma) must be identified, and cardiovascular and GI risk must be assessed before using these agents as chemopreventive drugs.

PMID: 19765361 [PubMed - in process]

(ROOT
  (S
    (SQ
      (NP (NNS NSAIDs))
      (VP (VB incur)
        (NP
          (ADJP
            (ADJP (JJ significant) (JJ gastrointestinal))
            (PRN (-LRB- -LRB-)
              (NP (NNP GI))
              (-RRB- -RRB-)))
          (NN side) (NNS effects))))
    (. .)
    (NP (DT The) (NN complication) (NN risk))
    (VP (VBZ increases)
      (PP (IN with)
        (NP
          (NP (NN history))
          (PP (IN of)
            (NP
              (NP (JJ peptic) (NN ulcer))
              (CC or)
              (NP (JJR older) (NN age)))))))
    (. .)))

nsubj(incur-2, NSAIDs-1)
dep(increases-14, incur-2)
amod(effects-9, significant-3)
dep(significant-3, gastrointestinal-4)
dep(significant-3, GI-6)
nn(effects-9, side-8)
dobj(incur-2, effects-9)
det(risk-13, The-11)
nn(risk-13, complication-12)
nsubj(increases-14, risk-13)
prep_with(increases-14, history-16)
amod(ulcer-19, peptic-18)
prep_of(history-16, ulcer-19)
amod(age-22, older-21)
conj_or(ulcer-19, age-22)
(ROOT
  (S
    (NP
      (NP (NNP Helicobacter) (NNP pylori) (NN infection))
      (CC and)
      (NP (NN cardioprotective) (NN aspirin)))
    (VP (VBP have)
      (NP
        (NP
          (ADJP (JJ independent)
            (CC and)
            (JJ additive))
          (NNS risks))
        (PP (IN in)
          (NP
            (NP (DT the) (NN presence))
            (PP (IN of)
              (NP (JJ NSAID) (NN use)))))))
    (. .)))

nn(infection-3, Helicobacter-1)
nn(infection-3, pylori-2)
nsubj(have-7, infection-3)
nn(aspirin-6, cardioprotective-5)
conj_and(infection-3, aspirin-6)
amod(risks-11, independent-8)
conj_and(independent-8, additive-10)
dobj(have-7, risks-11)
det(presence-14, the-13)
prep_in(risks-11, presence-14)
amod(use-17, NSAID-16)
prep_of(presence-14, use-17)
(ROOT
  (S
    (S
      (NP (NNP NSAID) (NN enteropathy))
      (VP (VBZ is)
        (ADJP (RB increasingly) (VBN recognized)))
      (. .))
    (NP (NNP Cardiovascular)
      (CC and)
      (NNP GI))
    (VP (VBP risk)
      (SBAR
        (S
          (NP
            (NP (NN stratification)
              (CC and)
              (NNP H.))
            (NNP pylori) (NN infection) (NN testing))
          (VP (MD should)
            (VP (VB be)
              (VP (VBN done)
                (PP (IN before)
                  (S
                    (VP (VBG initiating)
                      (NP (NNS NSAIDs)))))))))))
    (. .)))

nn(enteropathy-2, NSAID-1)
nsubjpass(recognized-5, enteropathy-2)
auxpass(recognized-5, is-3)
advmod(recognized-5, increasingly-4)
dep(risk-10, recognized-5)
nsubj(risk-10, Cardiovascular-7)
conj_and(Cardiovascular-7, GI-9)
nn(testing-16, stratification-11)
conj_and(stratification-11, H.-13)
nn(testing-16, pylori-14)
nn(testing-16, infection-15)
nsubjpass(done-19, testing-16)
aux(done-19, should-17)
auxpass(done-19, be-18)
ccomp(risk-10, done-19)
prepc_before(done-19, initiating-21)
dobj(initiating-21, NSAIDs-22)
(ROOT
  (S
    (S
      (NP
        (NP (DT An) (NN NSAID))
        (VP (VBN combined)
          (PP (IN with)
            (NP (DT a) (NN proton) (NN pump) (NN inhibitor))))
        (PRN (-LRB- -LRB-)
          (NP (NNP PPI))
          (-RRB- -RRB-)))
      (VP (VBZ is)
        (ADJP (JJ comparable)
          (S
            (VP (TO to)
              (VP (VB cyclooxygenase)
                (NP
                  (PRN (-LRB- -LRB-)
                    (NP (NNP COX))
                    (-RRB- -RRB-))
                  (JJ -2) (NNS inhibitors))
                (PP (IN for)
                  (NP (NN gastroprotection)))))))))
    (, ,)
    (CC but)
    (S
      (PP (IN for)
        (NP (JJ high-risk) (NNS patients)))
      (, ,)
      (NP (NNP COX-2)
        (CC plus)
        (NNP PPI))
      (VP (MD should)
        (VP (VB be)
          (VP (VBN considered)))))
    (. .)))

det(NSAID-2, An-1)
nsubj(comparable-13, NSAID-2)
partmod(NSAID-2, combined-3)
det(inhibitor-8, a-5)
nn(inhibitor-8, proton-6)
nn(inhibitor-8, pump-7)
prep_with(combined-3, inhibitor-8)
abbrev(NSAID-2, PPI-10)
cop(comparable-13, is-12)
aux(cyclooxygenase-15, to-14)
xcomp(comparable-13, cyclooxygenase-15)
abbrev(inhibitors-20, COX-17)
amod(inhibitors-20, -2-19)
dobj(cyclooxygenase-15, inhibitors-20)
prep_for(cyclooxygenase-15, gastroprotection-22)
amod(patients-27, high-risk-26)
prep_for(considered-34, patients-27)
nsubjpass(considered-34, COX-2-29)
conj_plus(COX-2-29, PPI-31)
aux(considered-34, should-32)
auxpass(considered-34, be-33)
conj_plus(comparable-13, considered-34)
(ROOT
  (S
    (S
      (NP
        (NP (NN Aspirin)
          (CC and)
          (NN COX-2))
        (NNS inhibitors))
      (VP (VBP are)
        (VP (VBN associated)
          (PP (IN with)
            (NP (VBN reduced) (NN colon) (NN adenoma) (NN risk))))))
    (, ,)
    (CC but)
    (S
      (NP
        (NP (JJR higher) (NN dose))
        (CC and)
        (NP
          (NP (JJR longer) (NN duration))
          (PP (IN of)
            (NP
              (NP (NN treatment))
              (PP (IN with)
                (NP (NN aspirin)))))))
      (VP (VBZ appears)
        (ADJP (JJ effective))))
    (. .)))

nn(inhibitors-4, Aspirin-1)
conj_and(Aspirin-1, COX-2-3)
nsubjpass(associated-6, inhibitors-4)
auxpass(associated-6, are-5)
amod(risk-11, reduced-8)
nn(risk-11, colon-9)
nn(risk-11, adenoma-10)
prep_with(associated-6, risk-11)
amod(dose-15, higher-14)
nsubj(effective-24, dose-15)
amod(duration-18, longer-17)
conj_and(dose-15, duration-18)
prep_of(duration-18, treatment-20)
prep_with(treatment-20, aspirin-22)
cop(effective-24, appears-23)
conj_and(associated-6, effective-24)
(ROOT
  (S
    (ADVP (RB Hence))
    (, ,)
    (S
      (NP
        (NP (NNS patients))
        (PP (IN at)
          (NP
            (NP (JJ high) (NN risk))
            (PP (IN of)
              (NP
                (NP (JJ colorectal) (NN cancer))
                (PRN (-LRB- -LRB-)
                  (PP (IN with)
                    (NP
                      (NP
                        (NP (JJ significant) (NN family))
                        (CC or)
                        (NP (JJ personal) (NN history)))
                      (PP (IN of)
                        (NP (JJ premalignant) (NN adenoma)))))
                  (-RRB- -RRB-)))))))
      (VP (MD must)
        (VP (VB be)
          (VP (VBN identified)))))
    (, ,)
    (CC and)
    (S
      (NP
        (NP (JJ cardiovascular))
        (CC and)
        (NP (NN GI) (NN risk)))
      (VP (MD must)
        (VP (VB be)
          (VP (VBN assessed)
            (PP (IN before)
              (S
                (VP (VBG using)
                  (NP (DT these) (NNS agents))
                  (PP (IN as)
                    (NP (JJ chemopreventive) (NNS drugs))))))))))
    (. .)))

advmod(identified-23, Hence-1)
nsubjpass(identified-23, patients-3)
amod(risk-6, high-5)
prep_at(patients-3, risk-6)
amod(cancer-9, colorectal-8)
prep_of(risk-6, cancer-9)
dep(cancer-9, with-11)
amod(family-13, significant-12)
pobj(with-11, family-13)
amod(history-16, personal-15)
conj_or(family-13, history-16)
amod(adenoma-19, premalignant-18)
prep_of(family-13, adenoma-19)
aux(identified-23, must-21)
auxpass(identified-23, be-22)
nsubjpass(assessed-32, cardiovascular-26)
nn(risk-29, GI-28)
conj_and(cardiovascular-26, risk-29)
aux(assessed-32, must-30)
auxpass(assessed-32, be-31)
conj_and(identified-23, assessed-32)
prepc_before(assessed-32, using-34)
det(agents-36, these-35)
dobj(using-34, agents-36)
amod(drugs-39, chemopreventive-38)
prep_as(using-34, drugs-39)

その3

1: Cancer Epidemiol Biomarkers Prev. 2009 Sep 15.

Cyclooxygenase-2 Polymorphisms, Aspirin Treatment, and Risk for Colorectal Adenoma Recurrence--Data from a Randomized Clinical Trial.

Barry EL, Sansbury LB, Grau MV, Ali IU, Tsang S, Munroe DJ, Ahnen DJ, Sandler RS, Saibil F, Gui J, Bresalier RS, McKeown-Eyssen GE, Burke C, Baron JA.

Departments of 1Community and Family Medicine and 2Medicine, Dartmouth Medical School, Lebanon, New Hampshire; Divisions of 3Cancer Control and Population Sciences and 4Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland; 5Laboratory of Molecular Technology, Science Applications International Corporation, Inc., Frederick, Maryland; 6Department of Medicine, University of Colorado, Denver, Colorado; 7Department of Medicine, University of North Carolina, Chapel Hill, North Carolina; 8Division of Gastroenterology, Sunnybrook Health Sciences Centre; 9Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; 10Department of Gastroenterology, Hepatology and Nutrition, M.D. Anderson Cancer Center, Houston, Texas; and 11Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio.

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the production of prostaglandins, potent mediators of inflammation. Chronic inflammation plays an important role in the development and progression of colorectal cancer. Aspirin inhibits COX-2 activity and lowers the risk for colorectal adenomas and cancer. We investigated whether common genetic variation in COX-2 influenced risk for colorectal adenoma recurrence among 979 participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or aspirin and followed for 3 years for the occurrence of new adenomas. Of these participants, 44.2% developed at least one new adenoma during follow-up. Adjusted relative risks and 95% confidence intervals (95% CI) were calculated to test the association between genetic variation at six COX-2 single-nucleotide polymorphisms and adenoma occurrence and interaction with aspirin treatment. Two single-nucleotide polymorphisms were significantly associated with increased adenoma recurrence: for rs5277, homozygous carriers of the minor C allele had a 51% increased risk compared with GG homozygotes (relative risk, 1.51; 95% CI, 1.01-2.25), and for rs4648310, heterozygous carriers of the minor G allele had a 37% increased risk compared with AA homozygotes (relative risk, 1.37; 95% CI, 1.05-1.79). (There were no minor allele homozygotes.) In stratified analyses, there was suggestive evidence that rs4648319 modified the effect of aspirin. These results support the hypothesis that COX-2 plays a role in the etiology of colon cancer and may be a target for aspirin chemoprevention and warrant further investigation in other colorectal adenoma and cancer populations.(Cancer Epidemiol Biomarkers Prev 2009;18(10):OF1-8).

PMID: 19755647 [PubMed - as supplied by publisher]

(ROOT
  (S
    (NP
      (NP (NN Cyclooxygenase-2))
      (PRN (-LRB- -LRB-)
        (NP (NN COX-2))
        (-RRB- -RRB-)))
    (VP (VBZ catalyzes)
      (NP
        (NP (DT the) (JJ rate-limiting) (NN step))
        (PP (IN in)
          (NP
            (NP (DT the) (NN production))
            (PP (IN of)
              (NP
                (NP (NNS prostaglandins))
                (, ,)
                (NP
                  (NP (JJ potent) (NNS mediators))
                  (PP (IN of)
                    (NP (NN inflammation))))))))))
    (. .)))

nsubj(catalyzes-5, Cyclooxygenase-2-1)
appos(Cyclooxygenase-2-1, COX-2-3)
det(step-8, the-6)
amod(step-8, rate-limiting-7)
dobj(catalyzes-5, step-8)
det(production-11, the-10)
prep_in(step-8, production-11)
prep_of(production-11, prostaglandins-13)
amod(mediators-16, potent-15)
appos(prostaglandins-13, mediators-16)
prep_of(mediators-16, inflammation-18)
(ROOT
  (S
    (NP (JJ Chronic) (NN inflammation))
    (VP (VBZ plays)
      (NP
        (NP (DT an) (JJ important) (NN role))
        (PP (IN in)
          (NP
            (NP (DT the) (NN development)
              (CC and)
              (NN progression))
            (PP (IN of)
              (NP (JJ colorectal) (NN cancer)))))))
    (. .)))

amod(inflammation-2, Chronic-1)
nsubj(plays-3, inflammation-2)
det(role-6, an-4)
amod(role-6, important-5)
dobj(plays-3, role-6)
det(development-9, the-8)
prep_in(role-6, development-9)
conj_and(development-9, progression-11)
amod(cancer-14, colorectal-13)
prep_of(development-9, cancer-14)
(ROOT
  (S
    (NP (NNP Aspirin))
    (VP
      (VP (VBZ inhibits)
        (NP (NN COX-2) (NN activity)))
      (CC and)
      (VP (VBZ lowers)
        (NP
          (NP (DT the) (NN risk))
          (PP (IN for)
            (NP (JJ colorectal) (NNS adenomas)
              (CC and)
              (NN cancer))))))
    (. .)))

nsubj(inhibits-2, Aspirin-1)
nn(activity-4, COX-2-3)
dobj(inhibits-2, activity-4)
conj_and(inhibits-2, lowers-6)
det(risk-8, the-7)
dobj(lowers-6, risk-8)
amod(adenomas-11, colorectal-10)
prep_for(risk-8, adenomas-11)
conj_and(adenomas-11, cancer-13)
(ROOT
  (S
    (NP (PRP We))
    (VP (VBD investigated)
      (SBAR (IN whether)
        (S
          (NP
            (NP (JJ common) (JJ genetic) (NN variation))
            (PP (IN in)
              (NP (NN COX-2))))
          (VP (VBD influenced)
            (NP (NN risk))
            (PP (IN for)
              (NP (JJ colorectal) (NN adenoma) (NN recurrence)))
            (PP (IN among)
              (NP
                (NP (CD 979) (NNS participants))
                (PP (IN in)
                  (NP (DT the) (NNP Aspirin\/Folate) (NNP Polyp) (NNP Prevention) (NNP Study)))
                (SBAR
                  (WHNP (WP who))
                  (S
                    (VP (VBD were)
                      (ADVP (RB randomly))
                      (VP
                        (VP (VBN assigned)
                          (PP (TO to)
                            (NP (NN placebo)
                              (CC or)
                              (NN aspirin))))
                        (CC and)
                        (VP (VBN followed)
                          (PP (IN for)
                            (NP
                              (NP (CD 3) (NNS years))
                              (PP (IN for)
                                (NP
                                  (NP (DT the) (NN occurrence))
                                  (PP (IN of)
                                    (NP (JJ new) (NNS adenomas))))))))))))))))))
    (. .)))

nsubj(investigated-2, We-1)
complm(influenced-9, whether-3)
amod(variation-6, common-4)
amod(variation-6, genetic-5)
nsubj(influenced-9, variation-6)
prep_in(variation-6, COX-2-8)
ccomp(investigated-2, influenced-9)
dobj(influenced-9, risk-10)
amod(recurrence-14, colorectal-12)
nn(recurrence-14, adenoma-13)
prep_for(influenced-9, recurrence-14)
num(participants-17, 979-16)
prep_among(influenced-9, participants-17)
det(Study-23, the-19)
nn(Study-23, Aspirin\/Folate-20)
nn(Study-23, Polyp-21)
nn(Study-23, Prevention-22)
prep_in(participants-17, Study-23)
rel(assigned-27, who-24)
auxpass(assigned-27, were-25)
advmod(assigned-27, randomly-26)
rcmod(participants-17, assigned-27)
prep_to(assigned-27, placebo-29)
conj_or(placebo-29, aspirin-31)
conj_and(assigned-27, followed-33)
num(years-36, 3-35)
prep_for(followed-33, years-36)
det(occurrence-39, the-38)
prep_for(years-36, occurrence-39)
amod(adenomas-42, new-41)
prep_of(occurrence-39, adenomas-42)
(ROOT
  (S
    (PP (IN Of)
      (NP (DT these) (NNS participants)))
    (, ,)
    (NP (CD 44.2) (NN %))
    (VP (VBD developed)
      (NP
        (QP
          (XS (IN at) (JJS least))
          (CD one))
        (JJ new) (NN adenoma))
      (PP (IN during)
        (NP (NNP follow-up))))
    (. .)))

det(participants-3, these-2)
prep_of(developed-7, participants-3)
num(%-6, 44.2-5)
nsubj(developed-7, %-6)
quantmod(one-10, at-8)
dep(at-8, least-9)
num(adenoma-12, one-10)
amod(adenoma-12, new-11)
dobj(developed-7, adenoma-12)
prep_during(developed-7, follow-up-14)
(ROOT
  (S
    (NP
      (NP (JJ Adjusted) (JJ relative) (NNS risks))
      (CC and)
      (NP
        (NP
          (ADJP (CD 95) (NN %))
          (NN confidence) (NNS intervals))
        (PRN (-LRB- -LRB-)
          (ADJP
            (NP (CD 95) (NN %))
            (JJ CI))
          (-RRB- -RRB-))))
    (VP (VBD were)
      (VP (VBN calculated)
        (S
          (VP (TO to)
            (VP (VB test)
              (NP
                (NP (DT the) (NN association))
                (PP (IN between)
                  (NP (JJ genetic) (NN variation))))
              (PP (IN at)
                (NP
                  (NP (CD six) (NN COX-2) (JJ single-nucleotide) (NNS  polymorphisms))
                  (CC and)
                  (NP (NN adenoma) (NN occurrence)
                    (CC and)
                    (NN interaction))))
              (PP (IN with)
                (NP (NN aspirin) (NN treatment))))))))
    (. .)))

amod(risks-3, Adjusted-1)
amod(risks-3, relative-2)
nsubjpass(calculated-15, risks-3)
dep(%-6, 95-5)
amod(intervals-8, %-6)
nn(intervals-8, confidence-7)
conj_and(risks-3, intervals-8)
num(%-11, 95-10)
measure(CI-12, %-11)
dep(intervals-8, CI-12)
auxpass(calculated-15, were-14)
aux(test-17, to-16)
xcomp(calculated-15, test-17)
det(association-19, the-18)
dobj(test-17, association-19)
amod(variation-22, genetic-21)
prep_between(association-19, variation-22)
num(polymorphisms-27, six-24)
nn(polymorphisms-27, COX-2-25)
amod(polymorphisms-27, single-nucleotide-26)
prep_at(test-17, polymorphisms-27)
nn(occurrence-30, adenoma-29)
conj_and(polymorphisms-27, occurrence-30)
conj_and(occurrence-30, interaction-32)
nn(treatment-35, aspirin-34)
prep_with(test-17, treatment-35)
(ROOT
  (S
    (S
      (NP (CD Two) (JJ single-nucleotide) (NNS polymorphisms))
      (VP (VBD were)
        (ADVP (RB significantly))
        (VP (VBN associated)
          (PP (IN with)
            (NP (VBN increased) (NN adenoma) (NN recurrence))))))
    (: :)
    (S
      (S
        (PP (IN for)
          (NP (NN rs5277)))
        (, ,)
        (NP
          (NP (JJ homozygous) (NNS carriers))
          (PP (IN of)
            (NP (DT the) (JJ minor) (NN C) (NN allele))))
        (VP (VBD had)
          (NP (DT a)
            (ADJP (CD 51) (NN %))
            (JJ increased) (NN risk))
          (PP (VBN compared)
            (PP (IN with)
              (NP
                (NP (NN GG) (NNS homozygotes))
                (PRN (-LRB- -LRB-)
                  (NP
                    (NP (JJ relative) (NN risk))
                    (, ,)
                    (NP
                      (NP (CD 1.51))
                      (: ;)
                      (NP
                        (ADJP (CD 95) (NN %))
                        (NN CI)))
                    (, ,)
                    (NP (CD 1.01) (CD -2.25)))
                  (-RRB- -RRB-)))))))
      (, ,)
      (CC and)
      (S
        (PP (IN for)
          (NP (NN rs4648310)))
        (, ,)
        (NP
          (NP (JJ heterozygous) (NNS carriers))
          (PP (IN of)
            (NP (DT the) (JJ minor) (NN G) (NN allele))))
        (VP (VBD had)
          (NP (DT a)
            (ADJP
              (NP (CD 37) (NN %))
              (JJ increased))
            (NN risk))
          (PP (VBN compared)
            (PP (IN with)
              (NP
                (NP (NN AA) (NNS homozygotes))
                (PRN (-LRB- -LRB-)
                  (NP
                    (NP (JJ relative) (NN risk))
                    (, ,)
                    (NP
                      (NP (CD 1.37))
                      (: ;)
                      (NP
                        (ADJP (CD 95) (NN %))
                        (NN CI)))
                    (, ,)
                    (NP (CD 1.05) (CD -1.79)))
                  (-RRB- -RRB-))))))))
    (. .)))

num(polymorphisms-3, Two-1)
amod(polymorphisms-3, single-nucleotide-2)
nsubjpass(associated-6, polymorphisms-3)
auxpass(associated-6, were-4)
advmod(associated-6, significantly-5)
amod(recurrence-10, increased-8)
nn(recurrence-10, adenoma-9)
prep_with(associated-6, recurrence-10)
prep_for(had-22, rs5277-13)
amod(carriers-16, homozygous-15)
nsubj(had-22, carriers-16)
det(allele-21, the-18)
amod(allele-21, minor-19)
nn(allele-21, C-20)
prep_of(carriers-16, allele-21)
parataxis(associated-6, had-22)
det(risk-27, a-23)
dep(%-25, 51-24)
amod(risk-27, %-25)
amod(risk-27, increased-26)
dobj(had-22, risk-27)
prep(had-22, compared-28)
dep(compared-28, with-29)
nn(homozygotes-31, GG-30)
pobj(with-29, homozygotes-31)
amod(risk-34, relative-33)
dep(homozygotes-31, risk-34)
appos(risk-34, 1.51-36)
dep(%-39, 95-38)
amod(CI-40, %-39)
dep(1.51-36, CI-40)
num(-2.25-43, 1.01-42)
appos(risk-34, -2.25-43)
prep_for(had-57, rs4648310-48)
amod(carriers-51, heterozygous-50)
nsubj(had-57, carriers-51)
det(allele-56, the-53)
amod(allele-56, minor-54)
nn(allele-56, G-55)
prep_of(carriers-51, allele-56)
conj_and(had-22, had-57)
det(risk-62, a-58)
num(%-60, 37-59)
measure(increased-61, %-60)
amod(risk-62, increased-61)
dobj(had-57, risk-62)
nn(homozygotes-66, AA-65)
prep_compared_with(had-57, homozygotes-66)
amod(risk-69, relative-68)
dep(homozygotes-66, risk-69)
appos(risk-69, 1.37-71)
dep(%-74, 95-73)
amod(CI-75, %-74)
dep(1.37-71, CI-75)
num(-1.79-78, 1.05-77)
appos(risk-69, -1.79-78)
(ROOT
  (S (-LRB- -LRB-)
    (NP (EX There))
    (VP (VBD were)
      (NP (DT no) (JJ minor) (NN allele) (NNS homozygotes)))
    (. .) (-RRB- -RRB-)))

expl(were-3, There-2)
det(homozygotes-7, no-4)
amod(homozygotes-7, minor-5)
nn(homozygotes-7, allele-6)
nsubj(were-3, homozygotes-7)
(ROOT
  (S
    (PP (IN In)
      (NP (JJ stratified) (NNS analyses)))
    (, ,)
    (NP (EX there))
    (VP (VBD was)
      (NP (JJ suggestive) (NN evidence))
      (SBAR (IN that)
        (S
          (NP (NNS rs4648319))
          (VP (VBN modified)
            (NP
              (NP (DT the) (NN effect))
              (PP (IN of)
                (NP (NN aspirin))))))))
    (. .)))

amod(analyses-3, stratified-2)
prep_in(was-6, analyses-3)
expl(was-6, there-5)
amod(evidence-8, suggestive-7)
nsubj(was-6, evidence-8)
complm(modified-11, that-9)
nsubj(modified-11, rs4648319-10)
ccomp(was-6, modified-11)
det(effect-13, the-12)
dobj(modified-11, effect-13)
prep_of(effect-13, aspirin-15)
(ROOT
  (S
    (NP (DT These) (NNS results))
    (VP (VBP support)
      (NP (DT the) (NN hypothesis))
      (SBAR (IN that)
        (S
          (NP (NN COX-2))
          (VP
            (VP (VBZ plays)
              (NP (DT a) (NN role))
              (PP (IN in)
                (NP
                  (NP (DT the) (NN etiology))
                  (PP (IN of)
                    (NP (NN colon) (NN cancer))))))
            (CC and)
            (VP (MD may)
              (VP
                (VP (VB be)
                  (NP
                    (NP (DT a) (NN target))
                    (PP (IN for)
                      (NP (NN aspirin) (NN chemoprevention)))))
                (CC and)
                (VP (VB warrant)
                  (NP
                    (NP
                      (NP (JJ further) (NN investigation))
                      (PP (IN in)
                        (NP
                          (NP (JJ other) (JJ colorectal) (NN adenoma))
                          (CC and)
                          (NP (NN cancer) (NNS populations))))
                      (. .))
                    (PRN (-LRB- -LRB-)
                      (FRAG
                        (NP-TMP
                          (NP (NNP Cancer) (NNP Epidemiol) (NNPS Biomarkers)  (NNP Prev))
                          (NP (CD 2009)))
                        (: ;)
                        (NP
                          (NP (CD 18) (CD (10)))
                          (: :)
                          (NP (NN OF1-8))))
                      (-RRB- -RRB-))))))))))
    (. .)))

det(results-2, These-1)
nsubj(support-3, results-2)
det(hypothesis-5, the-4)
dobj(support-3, hypothesis-5)
complm(plays-8, that-6)
nsubj(plays-8, COX-2-7)
ccomp(support-3, plays-8)
det(role-10, a-9)
dobj(plays-8, role-10)
det(etiology-13, the-12)
prep_in(plays-8, etiology-13)
nn(cancer-16, colon-15)
prep_of(etiology-13, cancer-16)
aux(target-21, may-18)
cop(target-21, be-19)
det(target-21, a-20)
conj_and(plays-8, target-21)
nn(chemoprevention-24, aspirin-23)
prep_for(target-21, chemoprevention-24)
conj_and(target-21, warrant-26)
amod(investigation-28, further-27)
dobj(warrant-26, investigation-28)
amod(adenoma-32, other-30)
amod(adenoma-32, colorectal-31)
prep_in(investigation-28, adenoma-32)
nn(populations-35, cancer-34)
conj_and(adenoma-32, populations-35)
nn(Prev-41, Cancer-38)
nn(Prev-41, Epidemiol-39)
nn(Prev-41, Biomarkers-40)
dep(-LRB--37, Prev-41)
dep(Prev-41, 2009-42)
num((10)-45, 18-44)
dep(Prev-41, (10)-45)
dep((10)-45, OF1-8-47)

その4

1: J Clin Oncol. 2009 Sep 20;27(27):4542-7. Epub 2009 Aug 24.

Use of hormone replacement therapy and the risk of colorectal cancer.

Rennert G, Rennert HS, Pinchev M, Lavie O, Gruber SB.

Department of Community Medicine and Epidemiology, Carmel Medical Center, 7 Michal St, Haifa 34362, Israel. rennert@tx.technion.ac.il

PURPOSE: Estrogen/progestin replacement therapy is prescribed to women in menopause for purposes of postmenopausal symptom control or prevention of hormone deficiency-related diseases such as osteoporosis. Such treatments have formerly been shown to be associated with lower colorectal cancer risk in an as yet unknown mechanism. PATIENTS AND METHODS: The Molecular Epidemiology of Colorectal Cancer study was a population-based case-control study in northern Israel of patients with colorectal cancer who were diagnosed between 1998 and 2006, and age-, sex-, clinic-, and ethnicity-matched population controls. Use of hormone replacement therapy (HRT) was assessed using a structured interview and validated by studying prescription records in a subset of patients for whom they were available. RESULTS: Two thousand four hundred sixty peri/postmenopausal women were studied from among 2,648 patients with colorectal cancer and 2,566 controls. The self-reported use of HRT was associated with a significantly reduced relative risk of colorectal cancer (odds ratio [OR], 0.67; 95% CI, 0.51 to 0.89). This association remained significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of colorectal cancer, ethnic group, and level of vegetable consumption (OR, 0.37; 95% CI, 0.22 to 0.62). Statistically significant interactions were seen between use of HRT and use of aspirin and involvement in sports activity. Using pharmacy data, only users of combined oral preparations demonstrated a significant negative association with colorectal cancer. CONCLUSION: The use of oral HRT was associated with a 63% relative reduction in the risk of colorectal cancer in postmenopausal women after adjustment for other known risk factors. This effect was not found in aspirin users and women with intensive sports participation.

PMID: 19704062 [PubMed - in process]

(ROOT
  (FRAG
    (NP (NNP PURPOSE))
    (: :)
    (S
      (NP (NNP Estrogen\/progestin) (NN replacement) (NN therapy))
      (VP (VBZ is)
        (VP (VBN prescribed)
          (PP (TO to)
            (NP
              (NP (NNS women))
              (PP (IN in)
                (NP
                  (NP
                    (ADJP (JJ menopause)
                      (PP (IN for)
                        (NP
                          (NP
                            (NP (NNS purposes))
                            (PP (IN of)
                              (NP (JJ postmenopausal) (NN symptom) (NN  control))))
                          (CC or)
                          (NP
                            (NP (NN prevention))
                            (PP (IN of)
                              (NP (NN hormone)))))))
                    (JJ deficiency-related) (NNS diseases))
                  (PP (JJ such) (IN as)
                    (NP (NNS osteoporosis))))))))))
    (. .)))

dep(prescribed-7, PURPOSE-1)
nn(therapy-5, Estrogen\/progestin-3)
nn(therapy-5, replacement-4)
nsubjpass(prescribed-7, therapy-5)
auxpass(prescribed-7, is-6)
prep_to(prescribed-7, women-9)
amod(diseases-23, menopause-11)
prep_for(menopause-11, purposes-13)
amod(control-17, postmenopausal-15)
nn(control-17, symptom-16)
prep_of(purposes-13, control-17)
conj_or(purposes-13, prevention-19)
prep_of(prevention-19, hormone-21)
amod(diseases-23, deficiency-related-22)
prep_in(women-9, diseases-23)
prep_such_as(diseases-23, osteoporosis-26)
(ROOT
  (S
    (NP (JJ Such) (NNS treatments))
    (VP (VBP have)
      (ADVP (RB formerly))
      (VP (VBN been)
        (VP (VBN shown)
          (S
            (VP (TO to)
              (VP (VB be)
                (VP (VBN associated)
                  (PP (IN with)
                    (NP
                      (NP (JJR lower) (JJ colorectal) (NN cancer) (NN risk))
                      (PP (IN in)
                        (NP (DT an)
                          (ADJP (RB as) (RB yet) (JJ unknown))
                          (NN mechanism))))))))))))
    (. .)))

amod(treatments-2, Such-1)
nsubjpass(shown-6, treatments-2)
aux(shown-6, have-3)
advmod(shown-6, formerly-4)
auxpass(shown-6, been-5)
aux(associated-9, to-7)
auxpass(associated-9, be-8)
xcomp(shown-6, associated-9)
amod(risk-14, lower-11)
amod(risk-14, colorectal-12)
nn(risk-14, cancer-13)
prep_with(associated-9, risk-14)
det(mechanism-20, an-16)
advmod(unknown-19, as-17)
advmod(unknown-19, yet-18)
amod(mechanism-20, unknown-19)
prep_in(risk-14, mechanism-20)
(ROOT
  (FRAG
    (NP (NNS PATIENTS)
      (CC AND)
      (NNS METHODS))
    (: :)
    (S
      (NP
        (NP (DT The) (NNP Molecular) (NNP Epidemiology))
        (PP (IN of)
          (NP (NNP Colorectal) (NNP Cancer) (NN study))))
      (VP (VBD was)
        (NP
          (NP
            (NP (DT a) (JJ population-based) (JJ case-control) (NN study))
            (PP (IN in)
              (NP (JJ northern) (NNP Israel)))
            (PP (IN of)
              (NP
                (NP (NNS patients))
                (PP (IN with)
                  (NP (JJ colorectal) (NN cancer)))
                (SBAR
                  (WHNP (WP who))
                  (S
                    (VP (VBD were)
                      (VP (VBN diagnosed)
                        (PP (IN between)
                          (NP (CD 1998)
                            (CC and)
                            (CD 2006))))))))))
          (, ,)
          (CC and)
          (NP
            (NP (NN age) (: -))
            (, ,)
            (NP (NN sex) (: -))
            (, ,)
            (NP (NN clinic) (: -))
            (, ,)
            (CC and)
            (NP (JJ ethnicity-matched) (NN population) (NNS controls))))))
    (. .)))

dep(study-16, PATIENTS-1)
conj_and(PATIENTS-1, METHODS-3)
det(Epidemiology-7, The-5)
nn(Epidemiology-7, Molecular-6)
nsubj(study-16, Epidemiology-7)
nn(study-11, Colorectal-9)
nn(study-11, Cancer-10)
prep_of(Epidemiology-7, study-11)
cop(study-16, was-12)
det(study-16, a-13)
amod(study-16, population-based-14)
amod(study-16, case-control-15)
amod(Israel-19, northern-18)
prep_in(study-16, Israel-19)
prep_of(study-16, patients-21)
amod(cancer-24, colorectal-23)
prep_with(patients-21, cancer-24)
rel(diagnosed-27, who-25)
auxpass(diagnosed-27, were-26)
rcmod(patients-21, diagnosed-27)
prep_between(diagnosed-27, 1998-29)
conj_and(1998-29, 2006-31)
conj_and(study-16, age-34)
conj_and(age-34, sex-37)
conj_and(age-34, clinic-40)
amod(controls-46, ethnicity-matched-44)
nn(controls-46, population-45)
conj_and(age-34, controls-46)
(ROOT
  (S
    (NP
      (NP
        (NAC (NNP Use)
          (PP (IN of)
            (NP (NN hormone))))
        (NN replacement) (NN therapy))
      (PRN (-LRB- -LRB-)
        (NP (NNP HRT))
        (-RRB- -RRB-)))
    (VP (VBD was)
      (VP
        (VP (VBN assessed)
          (S
            (VP (VBG using)
              (NP (DT a) (JJ structured) (NN interview)))))
        (CC and)
        (VP (VBN validated)
          (PP (IN by)
            (S
              (VP (VBG studying)
                (NP (NN prescription) (NNS records))
                (PP (IN in)
                  (NP
                    (NP (DT a) (NN subset))
                    (PP (IN of)
                      (NP
                        (NP (NNS patients))
                        (SBAR
                          (WHPP (IN for)
                            (WHNP (WP whom)))
                          (S
                            (NP (PRP they))
                            (VP (VBD were)
                              (ADJP (JJ available)))))))))))))))
    (. .)))

dep(therapy-5, Use-1)
dep(Use-1, of-2)
pobj(of-2, hormone-3)
nn(therapy-5, replacement-4)
nsubjpass(assessed-10, therapy-5)
abbrev(therapy-5, HRT-7)
auxpass(assessed-10, was-9)
xcomp(assessed-10, using-11)
det(interview-14, a-12)
amod(interview-14, structured-13)
dobj(using-11, interview-14)
conj_and(assessed-10, validated-16)
prepc_by(validated-16, studying-18)
nn(records-20, prescription-19)
dobj(studying-18, records-20)
det(subset-23, a-22)
prep_in(studying-18, subset-23)
prep_of(subset-23, patients-25)
rel(available-30, for-26)
dep(for-26, whom-27)
nsubj(available-30, they-28)
cop(available-30, were-29)
rcmod(patients-25, available-30)
(ROOT
  (NP
    (NP (NNS RESULTS))
    (: :)
    (NP
      (NP (CD Two) (CD thousand))
      (SBAR
        (S
          (NP
            (QP (CD four) (CD hundred))
            (JJ sixty) (NN peri\/postmenopausal) (NNS women))
          (VP (VBD were)
            (VP (VBN studied)
              (PP (IN from) (IN among)
                (NP
                  (NP (CD 2,648) (NNS patients))
                  (PP (IN with)
                    (NP
                      (NP (JJ colorectal) (NN cancer))
                      (CC and)
                      (NP (CD 2,566) (NNS controls)))))))))))
    (. .)))

num(thousand-4, Two-3)
dep(RESULTS-1, thousand-4)
number(hundred-6, four-5)
num(women-9, hundred-6)
amod(women-9, sixty-7)
nn(women-9, peri\/postmenopausal-8)
nsubjpass(studied-11, women-9)
auxpass(studied-11, were-10)
rcmod(thousand-4, studied-11)
dep(studied-11, from-12)
num(patients-15, 2,648-14)
prep_among(studied-11, patients-15)
amod(cancer-18, colorectal-17)
prep_with(patients-15, cancer-18)
num(controls-21, 2,566-20)
conj_and(cancer-18, controls-21)
(ROOT
  (S
    (NP
      (NP (DT The) (JJ self-reported) (NN use))
      (PP (IN of)
        (NP (NNP HRT))))
    (VP (VBD was)
      (VP (VBN associated)
        (PP (IN with)
          (NP
            (NP (DT a) (RB significantly) (VBN reduced) (JJ relative) (NN risk))
            (PP (IN of)
              (NP
                (NP (JJ colorectal) (NN cancer))
                (PRN (-LRB- -LRB-)
                  (NP
                    (NP
                      (NP (NNS odds))
                      (NP
                        (NP (NN ratio))
                        (PRN (-LRB- -LRB-)
                          (NP (NNP OR))
                          (-RRB- -RRB-))))
                    (, ,)
                    (NP
                      (NP (CD 0.67))
                      (: ;)
                      (NP
                        (ADJP (CD 95) (NN %))
                        (NN CI)))
                    (, ,)
                    (NP
                      (NP (CD 0.51))
                      (PP (TO to)
                        (NP (NNP 0.89)))))
                  (-RRB- -RRB-))))))))
    (. .)))

det(use-3, The-1)
amod(use-3, self-reported-2)
nsubjpass(associated-7, use-3)
prep_of(use-3, HRT-5)
auxpass(associated-7, was-6)
det(risk-13, a-9)
advmod(risk-13, significantly-10)
amod(risk-13, reduced-11)
amod(risk-13, relative-12)
prep_with(associated-7, risk-13)
amod(cancer-16, colorectal-15)
prep_of(risk-13, cancer-16)
dep(cancer-16, odds-18)
dep(odds-18, ratio-19)
abbrev(ratio-19, OR-21)
appos(odds-18, 0.67-24)
dep(%-27, 95-26)
amod(CI-28, %-27)
dep(0.67-24, CI-28)
appos(odds-18, 0.51-30)
prep_to(0.51-30, 0.89-32)
(ROOT
  (SINV
    (S
      (NP (DT This) (NN association))
      (VP (VBD remained)
        (NP
          (NP
            (ADJP (JJ significant)
              (PP (IN after)
                (NP
                  (NP (NN adjustment))
                  (PP (IN for)
                    (NP
                      (NP (NN age))
                      (, ,)
                      (NP (NN sex))
                      (, ,))))))
            (NN use))
          (PP (IN of)
            (NP (NN aspirin)
              (CC and)
              (NNS statins))))))
    (, ,)
    (VP (VBZ sports))
    (NP
      (NP (NN activity))
      (, ,)
      (NP
        (NP (NN family) (NN history))
        (PP (IN of)
          (NP
            (NP (JJ colorectal) (NN cancer))
            (, ,)
            (NP (JJ ethnic) (NN group))
            (, ,)
            (CC and)
            (NP
              (NP (NN level))
              (PP (IN of)
                (NP
                  (NP (NN vegetable) (NN consumption))
                  (PRN (-LRB- -LRB-)
                    (NP
                      (NP (NNP OR))
                      (, ,)
                      (NP
                        (NP (CD 0.37))
                        (: ;)
                        (NP
                          (ADJP (CD 95) (NN %))
                          (NN CI)))
                      (, ,)
                      (NP (CD 0.22) (TO to) (CD 0.62)))
                    (-RRB- -RRB-)))))))))
    (. .)))

det(association-2, This-1)
nsubj(use-12, association-2)
cop(use-12, remained-3)
amod(use-12, significant-4)
prep_after(significant-4, adjustment-6)
prep_for(adjustment-6, age-8)
appos(age-8, sex-10)
ccomp(sports-18, use-12)
prep_of(use-12, aspirin-14)
conj_and(aspirin-14, statins-16)
nsubj(sports-18, activity-19)
nn(history-22, family-21)
appos(activity-19, history-22)
amod(cancer-25, colorectal-24)
prep_of(history-22, cancer-25)
amod(group-28, ethnic-27)
conj_and(cancer-25, group-28)
conj_and(cancer-25, level-31)
nn(consumption-34, vegetable-33)
prep_of(level-31, consumption-34)
dep(consumption-34, OR-36)
appos(OR-36, 0.37-38)
dep(%-41, 95-40)
amod(CI-42, %-41)
dep(0.37-38, CI-42)
num(0.62-46, 0.22-44)
dep(0.62-46, to-45)
appos(OR-36, 0.62-46)
(ROOT
  (S
    (ADVP (RB Statistically))
    (PRN
      (S
        (NP (JJ significant) (NNS interactions))
        (VP (VBD were)
          (VP (VBN seen)
            (PP (IN between)
              (NP
                (NP
                  (NP (NN use))
                  (PP (IN of)
                    (NP (NN HRT)
                      (CC and)
                      (NN use)))
                  (PP (IN of)
                    (NP (NN aspirin)
                      (CC and)
                      (NN involvement)))
                  (PP (IN in)
                    (NP (NNS sports) (NN activity)))
                  (. .))
                (VP (VBG Using)
                  (NP (NN pharmacy) (NNS data))))))))
      (, ,))
    (NP
      (NP (JJ only) (NNS users))
      (PP (IN of)
         (NP (VBN combined) (JJ oral) (NNS preparations))))
    (VP (VBD demonstrated)
      (NP (DT a) (JJ significant) (JJ negative) (NN association))
      (PP (IN with)
        (NP (JJ colorectal) (NN cancer))))
    (. .)))

advmod(demonstrated-30, Statistically-1)
amod(interactions-3, significant-2)
nsubjpass(seen-5, interactions-3)
auxpass(seen-5, were-4)
parataxis(demonstrated-30, seen-5)
prep_between(seen-5, use-7)
prep_of(use-7, HRT-9)
conj_and(HRT-9, use-11)
prep_of(use-7, aspirin-13)
conj_and(aspirin-13, involvement-15)
nn(activity-18, sports-17)
prep_in(use-7, activity-18)
partmod(use-7, Using-20)
nn(data-22, pharmacy-21)
dobj(Using-20, data-22)
amod(users-25, only-24)
nsubj(demonstrated-30, users-25)
amod(preparations-29, combined-27)
amod(preparations-29, oral-28)
prep_of(users-25, preparations-29)
det(association-34, a-31)
amod(association-34, significant-32)
amod(association-34, negative-33)
dobj(demonstrated-30, association-34)
amod(cancer-37, colorectal-36)
prep_with(demonstrated-30, cancer-37)
(ROOT
  (S
    (NP
      (NP
        (NP (NNP CONCLUSION))
        (: :)
        (S
          (NP
            (NP (DT The) (NN use))
            (PP (IN of)
              (NP (JJ oral) (NN HRT))))
          (VP (VBD was)
            (VP (VBN associated)
              (PP (IN with)
                (NP
                  (NP (DT a)
                    (ADJP (CD 63) (NN %))
                    (JJ relative) (NN reduction))
                  (PP (IN in)
                    (NP
                      (NP (DT the) (NN risk))
                      (PP (IN of)
                        (NP
                          (NP (JJ colorectal) (NN cancer))
                          (PP (IN in)
                            (NP (JJ postmenopausal) (NNS women)))))))))
              (PP (IN after)
                (NP
                  (NP (NN adjustment))
                  (PP (IN for)
                    (NP (JJ other) (JJ known) (NN risk) (NNS factors)))))))
          (. .)))
      (NP (DT This) (NN effect)))
    (VP (VBD was) (RB not)
      (VP (VBN found)
        (PP (IN in)
          (NP (NN aspirin) (NNS users)
            (CC and)
            (NNS women)))
        (PP (IN with)
          (NP (JJ intensive) (NNS sports) (NN participation)))))
    (. .))) 

nsubjpass(found-37, CONCLUSION-1)
det(use-4, The-3)
nsubjpass(associated-9, use-4)
amod(HRT-7, oral-6)
prep_of(use-4, HRT-7)
auxpass(associated-9, was-8)
dep(CONCLUSION-1, associated-9)
det(reduction-15, a-11)
dep(%-13, 63-12)
amod(reduction-15, %-13)
amod(reduction-15, relative-14)
prep_with(associated-9, reduction-15)
det(risk-18, the-17)
prep_in(reduction-15, risk-18)
amod(cancer-21, colorectal-20)
prep_of(risk-18, cancer-21)
amod(women-24, postmenopausal-23)
prep_in(cancer-21, women-24)
prep_after(associated-9, adjustment-26)
amod(factors-31, other-28)
amod(factors-31, known-29)
nn(factors-31, risk-30)
prep_for(adjustment-26, factors-31)
det(effect-34, This-33)
dep(CONCLUSION-1, effect-34)
auxpass(found-37, was-35)
neg(found-37, not-36)
nn(users-40, aspirin-39)
prep_in(found-37, users-40)
conj_and(users-40, women-42)
amod(participation-46, intensive-44)
nn(participation-46, sports-45)
prep_with(found-37, participation-46)

その5

1: Eur J Cancer. 2009 Aug 18.

APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the Apc(Min) mouse model in vivo.

Sale S, Fong IL, de Giovanni C, Landuzzi L, Brown K, Steward WP, Gescher AJ.

Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK.

Apc(Min) mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from Apc(Min) mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the Apc(Min) mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3',4',5',5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3',4',5'-trimethoxychalcone (DMU135), 3,4,5,4'-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all-trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC(50) values were calculated. The IC(50) values were plotted against previously published data of reduction of adenoma numbers caused by these agents in Apc(Min) mice. The correlation co-efficient was 0.678 (p<0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in Apc(Min) mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.

PMID: 19695862 [PubMed - as supplied by publisher]

その6

1: JAMA. 2009 Aug 12;302(6):649-58.

Aspirin use and survival after diagnosis of colorectal cancer.

Chan AT, Ogino S, Fuchs CS.

Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, GRJ 722 Boston, MA 02114, USA. achan@partners.org

CONTEXT: Aspirin reduces risk of colorectal neoplasia in randomized trials and inhibits tumor growth and metastases in animal models. However, the influence of aspirin on survival after diagnosis of colorectal cancer is unknown. OBJECTIVE: To examine the association between aspirin use after colorectal cancer diagnosis on colorectal cancer-specific and overall survival. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 1279 men and women diagnosed with stage I, II, or III colorectal cancer. Participants were enrolled in 2 nationwide health professional cohorts in 1980 and 1986 prior to diagnosis and followed up through June 1, 2008. MAIN OUTCOME MEASURE: Colorectal cancer-specific and overall mortality. RESULTS: After a median follow-up of 11.8 years, there were 193 total deaths (35%) and 81 colorectal cancer-specific deaths (15%) among 549 participants who regularly used aspirin after colorectal cancer diagnosis, compared with 287 total deaths (39%) and 141 colorectal cancer-specific deaths (19%) among 730 participants who did not use aspirin. Compared with nonusers, participants who regularly used aspirin after diagnosis experienced a multivariate hazard ratio (HR) for colorectal cancer-specific mortality of 0.71 (95% confidence interval [CI], 0.53-0.95) and for overall mortality of 0.79 (95% CI, 0.65-0.97). Among 719 participants who did not use aspirin before diagnosis, aspirin use initiated after diagnosis was associated with a multivariate HR for colorectal cancer-specific mortality of 0.53 (95% CI, 0.33-0.86). Among 459 participants with colorectal cancers that were accessible for immunohistochemical assessment, the effect of aspirin differed significantly according to cyclooxygenase 2 (COX-2) expression (P for interaction = .04). Regular aspirin use after diagnosis was associated with a lower risk of colorectal cancer-specific mortality among participants in whom primary tumors overexpressed COX-2 (multivariate HR, 0.39; 95% CI, 0.20-0.76), whereas aspirin use was not associated with lower risk among those with primary tumors with weak or absent expression (multivariate HR, 1.22; 95% CI, 0.36-4.18). CONCLUSION: Regular aspirin use after the diagnosis of colorectal cancer is associated with lower risk of colorectal cancer-specific and overall mortality, especially among individuals with tumors that overexpress COX-2.

PMID: 19671906 [PubMed - indexed for MEDLINE]

その7

1: Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2310-7.

The association of lifestyle and dietary factors with the risk for serrated polyps of the colorectum.

Wallace K, Grau MV, Ahnen D, Snover DC, Robertson DJ, Mahnke D, Gui J, Barry EL, Summers RW, McKeown-Eyssen G, Haile RW, Baron JA.

Department of Community and Family Medicine, Dartmouth Medical School, Hanover, New Hamsphire, USA.

Some serrated polyps of the colorectum are likely preinvasive lesions, evolving through a newly recognized serrated pathway to colorectal cancer. To assess possible risk and protective factors for serrated polyps and particularly to explore differences in risk factors between polyps in the right and left colorectum, we pooled data from three large multicenter chemoprevention trials. A serrated polyp was defined broadly as any serrated lesion (hyperplastic, sessile serrated adenoma, "traditional" serrated adenoma, mixed adenoma) diagnosed during each trial's main treatment period of approximately 3 to 4 years. Using generalized linear regression, we computed risk ratios and 95% confidence intervals as measures of the association between risk for serrated polyps and demographic, lifestyle, and dietary variables. Of the 2,830 subjects that completed at least one follow-up exam after randomization, 675 (23.9%) had at least one left-sided serrated polyp and 261 (9.2%) had at least one right-sided lesion. In the left colorectum, obesity, cigarette smoking, dietary fat, total energy intake, and red meat intake were associated with an increased risk for serrated polyps. In the right colon, aspirin treatment was associated with a reduced risk and family history of polyps and folate treatment were associated with an increased risk for serrated polyps. Our results suggest that several common lifestyle and dietary variables are associated with risk for serrated polyps, and some of these may differ for the right and left colorectum.

PMID: 19661090 [PubMed - in process]

その8

1: Clin Gastroenterol Hepatol. 2009 Feb 3.

A Multi-Center Study of Prevalence and Risk Factors for Aberrant Crypt Foci.

Mutch MG, Mph RE, Fleshman JW, Rall CJ, Dry S, Seligson D, Charabaty A, Chia D, Dvm AU, Viner J, Hawk E, Pinsky PF.

Washington University, St Louis, MO.

INTRODUCTION:: Aberrant crypt foci (ACF) are the putative precursor of colorectal adenomas. However, there are limited data available on prevalence and risk factors for ACF. METHODS:: Subjects from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial were recruited for an ACF study, with subjects with adenoma history being over-sampled. Using a standardized protocol of magnified chromoendscopy with methylene blue staining (up to the middle rectal fold), ACF were photodocumented and removed for histologic evaluation. RESULTS:: 505 (66% male, 55% = 70 years) subjects from 4 institutions were examined; 42% had no adenoma, 32% had non-advanced distal adenoma and 25% had advanced distal adenoma at baseline PLCO examination (8.2 years prior to ACF exam on average). 68% of this population had =1 ACF, 43% had 1-3, 19% had 4-6, and 5% had =7. Baseline adenoma status was not associated with ACF prevalence (range 66-69%) or mean number (range 3.1-3.5). Of 143 endoscopic ACF examined histologically, 68.5% were confirmed to be ACF. In a logistic model, current (OR=2.6; 95% CI 1.2-5.6) and former smoking (OR=1.6; 95% CI 1.1-2.5) were associated with higher ACF prevalence; a BMI> 30 was associated with lower prevalence (OR=0.53; 95% CI 0.35-0.8). Age, gender, family history of colorectal cancer, and aspirin/NSAID use were not significantly associated with ACF prevalence. CONCLUSIONS:: ACF prevalence and number were not associated with adenoma history and only 68.5% of endoscopic ACF were confirmed histologically. These results raise concern about the use of ACF as a surrogate marker of colorectal cancer risk.

PMID: 19558990 [PubMed - as supplied by publisher]

その9

1: Int J Cancer. 2009 Oct 1;125(7):1698-704.

Tumor markers and rectal cancer: support for an inflammation-related pathway.

Slattery ML, Wolff RK, Herrick J, Caan BJ, Samowitz W.

Department of Medicine, University of Utah, Salt Lake City, UT 84108, USA. marty.slattery@hsc.utah.edu

Inflammation may be a key element in the etiology of colorectal cancer. In our study, we examine associations between factors related to inflammation and specific rectal cancer mutations. A population-based study of 750 rectal cancer cases with interview and tumor DNA were compared to 1,205 population-based controls. Study participants were from Utah and the Northern California Kaiser Permanente Medical Care Program. Tumor DNA was analyzed for TP53 and KRAS2 mutations and CpG Island methylator phenotype. We assessed how these tumor markers were associated with use of anti-inflammatory drugs, polymorphisms in the IL6 genes (rs1800795 and rs1800796) and dietary antioxidants. Ibuprofen-type drugs, IL6 polymorphisms (rs1800796) and dietary alpha-tocopherol and lycopene significantly altered likelihood of having a TP53 mutation. This was especially true for TP53 transversion mutations and dietary antioxidants (OR for beta-carotene 0.51 95% CI 0.27, 0.97, p trend 0.03; alpha-tocopherol 0.41 95% CI 0.20, 0.84, p trend 0.02) Beta-carotene and ibuprofen significantly altered risk of KRAS2 tumors. The associations between lutein and tocopherol and TP53 and KRAS2 mutations were modified by IL6 genotype. These results suggest that inflammation-related factors may have unique associations with various rectal tumor markers. Many factors involved in an inflammation-related pathway were associated with TP53 mutations and some dietary factors appeared to be modified by IL6 genotype.

PMID: 19452524 [PubMed - indexed for MEDLINE]

その10

1: Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1599-609.

MutL-homolog 1 expression and risk of incident, sporadic colorectal adenoma: search for prospective biomarkers of risk for colorectal cancer.

Sidelnikov E, Bostick RM, Flanders WD, Long Q, Cohen VL, Dash C, Seabrook ME, Fedirko V.

Department of Epidemiology, Emory University, Atlanta, GA 30322, USA.

To characterize the expression of the mismatch repair gene MutL-homolog 1 (MLH1) in normal colorectal crypts in humans, and assess parameters of its expression as a potential biomarker of risk for colorectal neoplasms, we conducted a pilot, colonoscopy-based case-control study (51 cases, 154 controls) of incident, sporadic colorectal adenoma. Biopsies of normal-appearing rectal, sigmoid, and ascending colon mucosa were procured, immunohistochemically processed for MLH1 protein, and analyzed using custom quantitative image analysis procedures. MLH1 expression in the ascending colon was, on average, 49% proportionally lower in cases than controls (P = 0.03), but there was little evidence for case-control differences in the rectum and sigmoid colon. In cases and controls, average MLH1 expression in the ascending colon tended to be lower with increased age [by 56% (P = 0.02) and 25% (P = 0.16), respectively, for those > or =55 years], and with a history of colorectal cancer in a first-degree relative (by 22% [P = 0.56] and 34% [P = 0.16], respectively). Among cases, but not controls, average MLH1 expression tended to be higher with current alcohol consumption, regular aspirin use, and higher total intakes of calcium, vitamin D, and folate. There was little indication of similar differences in the rectum. These preliminary data suggest that lower MLH1 expression in the normal colonic mucosa, at least in the ascending colon, may be associated with increased risk of incident, sporadic colorectal adenoma, as well as with modifiable risk factors for colorectal neoplasms, thus supporting further investigation of MLH1 expression as a potential "treatable" biomarker of risk for colorectal neoplasms.

PMID: 19423536 [PubMed - indexed for MEDLINE]


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