title: Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies.
abstract: Use of statins is hypothesized to reduce colorectal cancer risk but the evidence remains inconsistent. This may be partly explained by differential associations according to tumor location or molecular subtypes of colorectal cancer. We examined the association between statin use and colorectal cancer risk according to tumor location, KRAS mutation status, microsatellite instability (MSI) status, PTGS2 (COX-2) expression, or CpG island methylator phenotype (CIMP) status in two large prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study. We applied Cox regression to a competing risks analysis. We identified 1,818 colorectal cancers during 1990 to 2006. Compared with nonusers, current statin use was not associated with colorectal cancer [relative risk (RR) = 0.99, 95% CI = 0.86-1.14] or colon cancer (RR = 1.10, 95% CI = 0.94-1.29) but was inversely associated with rectal cancer (RR = 0.59, 95% CI = 0.41-0.84, P(heterogeneity) < 0.001). When we examined the association within strata of KRAS mutation status, we found no association with KRAS-mutated cancers (RR = 1.20, 95% CI = 0.87-1.67) but did observe a possible inverse association among KRAS wild-type cancers (RR = 0.80, 95% CI = 0.60-1.06, P(heterogeneity) = 0.06). The association did not substantially differ by PTGS2 expression, MSI status, or CIMP status. Current statin use was not associated with risk of overall colorectal cancer. The possibility that statin use may be associated with lower risk of rectal cancer or KRAS wild-type colorectal cancer requires further confirmation.
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Kimmie
authors.initials: K
authors.lastname: Ng
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D001900:Boston / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000145:classification / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D018899:CpG Islands / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins