Background: Colorectal cancer (CRC) is the third most common incident cancer among women in the United States. Alcohol use has been proposed as a CRC risk factor, but existing observational data remain inconsistent. To date, relatively few studies have examined associations between alcohol use and CRC risk based on molecularly‐defined subtypes.

Aim: To evaluate associations between alcohol use and incident CRC overall, as well as by molecularly‐defined subtypes including microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF mutation status in the prospective, population‐based, Iowa Women's Health Study (IWHS).

Methods: The IWHS recruited 41,836 randomly selected Iowa women, ages 55–69 years at enrollment, in 1986. Women with prevalent cancers or no follow‐up were excluded, leaving 38,001 eligible for this study. Alcohol use was obtained from a self‐administered food frequency questionnaire at study baseline. Incident CRCs were identified through annual linkage with the State Health Registry of Iowa. Archived, paraffin‐embedded tissue specimens were recently requested for incident CRC cases diagnosed through December 31, 2002. In the present study, useable tissue specimens were obtained and molecularly characterized for 563/1,255 cases (45%), whose baseline age, body mass index, physical activity level, total energy intake and alcohol use were similar to non‐retrieved cases (p > 0.05 for each comparison). Alcohol use was categorized as never (n=21,464), < 3.4 g/day (n=8,313) and > 3.4 g/day (n=8,224), based on the median split among users. Molecularly‐defined CRC subtypes were categorized as MSI‐high (MSIH; n=148), MSI‐low or microsatellite stable (MSI‐L/MSS; n=400); CIMP‐positive (n=167) or CIMP‐negative (n=368); and BRAF‐mutation (n=154) or BRAF‐wildtype (n=391). Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated for alcohol use compared to never drinkers, using multivariable Cox regression models adjusted for body mass index, waist‐to‐hip ratio, smoking status, physical activity level, exogenous estrogen use, and daily intakes of total energy, total fat, red meat, sucrose, calcium, folate, methionine and vitamin E.

Results: There was no statistically significant association between alcohol use and overall CRC risk (RR=1.00; 95% CI = 0.86–1.15 for < 3.4 g/day versus none; RR=1.06; 95% CI=0.91–1.24 for >3.4 g/day versus none). Further, there were no associations with alcohol use for specific, molecularly‐defined CRC subtypes (RRs shown for > 3.4 g/day versus none): MSI‐H (RR=1.07; 95% CI=0.70–1.64); MSI‐L or MSS (RR=1.12; 95% CI=0.85–1.47); CIMP‐positive (RR=0.97; 95% CI=0.64–1.47); CIMP‐negative (RR=1.13; 95% CI=0.85–1.50); BRAF‐mutation (RR=0.94; 95% CI=0.61–1.45); and BRAF‐wildtype (RR=1.20; 95% CI=0.91–1.57).

Conclusion: In this cohort of older women, alcohol use did not appear to be a risk factor for incident CRC, overall or by the defined molecular subtypes.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A115.

Copyright © January 7, 2010, American Association for Cancer Research
2010