Abstract A115: Alcohol use and molecularly defined colorectal cancer risks in a prospective study of older women
Authors: Razzak Anthony A. , Oxentenko Amy S. , Vierkant Robert A. , Tillmans Lori S. , Wang Alice H. , Weisenberger Daniel J. , Laird Peter W. , Lynch Charles F. , Anderson Kristin E. , Haile Robert W. , Harnack Lisa J. , Potter John D. , Slager Susan L. , Smyrk Thomas C. , Thibodeau Stephen N. , Cerhan James R. , Limburg Paul J. 
Published: May 2012

Abstract
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 &gt; 0.05 for each comparison). Alcohol use was categorized as never (n=21,464), &lt; 3.4 g/day (n=8,313) and &gt; 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 &lt; 3.4 g/day versus none; RR=1.06; 95% CI=0.91–1.24 for &gt;3.4 g/day versus none). Further, there were no associations with alcohol use for specific, molecularly-defined CRC subtypes (RRs shown for &gt; 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.