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-H or 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 55–69 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 (RRs) and 95% confidence intervals (CIs). Among alcohol consumers, the median intake (range) was 3.4 (0.9–292.8) g/day. Compared to non-consumers, alcohol intake levels of ≤ 3.4 g/day (RR = 1.00; 95% CI = 0.86–1.15) and > 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 and > 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.

Moderate Alcohol Consumption and Colorectal Cancer Risk

“…The present review found that the detrimental effect of high alcohol intake on the incidence of CRC was consistent with previous reports (Kontou et al, 2012;Park et al, 2009Park et al, , 2010; however, the results also suggested there was no increased risk for CRC when consuming up to 30 g/d of alcohol (Bongaerts et al, 2008;Grosso et al, 2014;Kontou et al, 2012;Nan et al, 2013;Park et al, 2010;Razzak et al, 2011;Zhao et al, 2012). The discrepancies between previous reports may be due to inappropriate stratification of alcohol intakes, with moderate intakes ranging from 12.6 to 49.9 g/d alcohol (Fedirko et al, 2011).…”

“…The reduced CRC risk associated with <30 g/d alcohol was found to be significant in only 2 studies: for nonobese individuals consuming between 13.5 and 27 g/d alcohol (Zhao et al, 2012), and for a Mediterranean population, where wine was a significant contributor to the alcoholic beverage type (Kontou et al, 2012). For all other studies, the risks associated with moderate alcohol consumption were not found to be statistically significant, but they consistently showed a reduced risk trend at moderate intake (Crockett et al, 2011;Nan et al, 2013;Park et al, 2010;Razzak et al, 2011).…”

“…A strength of this review was that the majority of studies reviewed used 30 g/d as the cutoff for the moderate reference intake, which was a more appropriate classification of moderate intake (Bongaerts et al, 2008;Crockett et al, 2011;Nan et al, 2013;Razzak et al, 2011). The studies that did not use the 30 g/d alcohol cutoff had slightly higher or lower reference points, while few included additional intake categories above 30 g/d, which allowed for even greater comparisons between the doses (Grosso et al, 2014;Kontou et al, 2012;Zhao et al, 2012).…”

“…Colonic bacteria are also able to metabolize alcohol into acetaldehyde, a carcinogenic byproduct, which chemically inactivates folate and leads to decreased levels in the colonic mucosa (Giovannucci, 2004). Folate plays an important role in one-carbon metabolism and influences DNA regulation (Razzak et al, 2011). Deficiencies caused by increased alcohol consumption could lead to abnormal tissue growth through altered DNA methylation or epigenetic modifications (Razzak et al, 2011), which potentially contribute to greater risk of developing CRC (Nan et al, 2013).…”

“…Folate plays an important role in one-carbon metabolism and influences DNA regulation (Razzak et al, 2011). Deficiencies caused by increased alcohol consumption could lead to abnormal tissue growth through altered DNA methylation or epigenetic modifications (Razzak et al, 2011), which potentially contribute to greater risk of developing CRC (Nan et al, 2013). In 1996, the U.S. Food and Drug Administration began mandating the addition of folic acid to grain and cereal products (Crockett et al, 2011).…”