title: Alcohol intake and colorectal cancer risk by molecularly defined subtypes in a prospective study of older women.
abstract: Increased alcohol consumption is a putative colorectal cancer (CRC) risk factor. However, existing data are less conclusive for women than men. Also, to date, relatively few studies have reported alcohol-related CRC risks based on molecularly defined tumor subtypes. We evaluated associations between alcohol intake and incident CRC, overall and by microsatellite instability [MSI high (MSI-H) or MSI low/microsatellite stable (MSI-L/MSS)], CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation (mutated or wild-type) status in the prospective, population-based Iowa Women's Health Study (IWHS; n = 41,836). Subjects were 55 to 69 years at baseline (1986), and exposure data were obtained by self-report. Incident CRCs were prospectively identified and archived, paraffin-embedded tissue specimens were collected from 732 representative cases, diagnosed through December 31, 2002. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Among alcohol consumers, the median intake (range) was 3.4 (0.9-292.8) g/d. Compared with nonconsumers, alcohol intake levels of 3.4 g/d or less (RR = 1.00; 95% CI, 0.86-1.15) and more than 3.4 g/d (RR = 1.06; 95% CI, 0.91-1.24) were not significantly associated with overall CRC risk. Analyses based on alcohol intake levels of 30 g/d or less and more than 30 g/d or quartile distributions yielded similar risk estimates. Null associations were also observed between each alcohol intake level and the MSI-, CIMP- or, BRAF-defined CRC subtypes (P > 0.05 for each comparison). These data do not support an adverse effect from alcohol intake on CRC risk, overall or by specific molecularly defined subtypes, among older women.
authors: Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors: Anthony A
authors: AA
authors: Razzak
authors: Amy S
authors: AS
authors: Oxentenko
authors: Robert A
authors: RA
authors: Vierkant
authors: Lori S
authors: LS
authors: Tillmans
authors: Alice H
authors: AH
authors: Wang
authors: Daniel J
authors: DJ
authors: Weisenberger
authors: Peter W
authors: PW
authors: Laird
authors: Charles F
authors: CF
authors: Lynch
authors: Kristin E
authors: KE
authors: Anderson
authors: Amy J
authors: AJ
authors: French
authors: Robert W
authors: RW
authors: Haile
authors: Lisa J
authors: LJ
authors: Harnack
authors: Susan L
authors: SL
authors: Slager
authors: Thomas C
authors: TC
authors: Smyrk
authors: Stephen N
authors: SN
authors: Thibodeau
authors: James R
authors: JR
authors: Cerhan
authors: Paul J
authors: PJ
authors: Limburg
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000145:classification* / Q000453:epidemiology* / Q000209:etiology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D015994:Incidence; D007484:Iowa / Q000453:epidemiology; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf