Alcohol Consumption and the Risk of Colorectal Cancer for Mismatch Repair Gene Mutation Carriers

Abstract

Background People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive. Methods 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol consumption and colorectal cancer. Results Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (standard deviation) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 grams/day and >28 grams/day were associated with increased colorectal cancer risk (HR, 1.50; 95%CI, 1.09–2.07 and 1.69; 95%CI, 1.07–2.65 respectively; P-trend=0.05), and colon cancer risk (HR, 1.78; 95%CI, 1.27–2.49 and 1.94; 95%CI, 1.19–3.18 respectively; P-trend=0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk. Conclusion Our data suggests that alcohol consumption, particularly more than 28 grams/day of ethanol (~2 standard drinks of alcohol in the US), is associated with increased colorectal cancer risk for MMR gene mutation carriers. Impact Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk.

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender

“…Diergaarde et al 73 Botma et al 74 Campbell et al 75 Movahedi et al 76 Win et al 77 These studies reported on the association between BMI and colorectal tumours in LS. A high BMI was associated with an increased risk of colorectal tumours in three publications 74,76,77 another 75 indicated an association in the same direction, and one 73 did not show an association Diergaarde et al 73 Kamiza et al 78 Watson et al 79 Winkels et al 80 Dashti et al 81 In analyses of alcohol consumption and colorectal tumour risk in LS, three studies 73,78,79 did not observe an association, one 80 demonstrated a possible increased risk, and one 81 reported a significant increase in risk of colorectal tumours when alcohol consumption was high Kamiza et al 78 The influence of physical activity on colorectal tumour risk has been investigated in only one study, which showed that being physically active is significantly associated with a decreased colorectal tumour risk in those with LS Brand et al 82 Diergaarde et al 73 Pande et al 83 Watson et al 79 Winkels et al 80 The risk of colorectal tumours is significantly increased by smoking in LS Diergaarde et al 73 Kamiza et al 78 Botma et al 74 Voskuil et al 84 Burn et al 85 Mathers et al 86 Jung et al 87 Chau et al 88 Heine-Bröring et al 89 Different aspects of diet, such as dietary patterns 74 , and consumption of meat 73,78,…”

Physical activity and the risk of colorectal cancer in Lynch syndrome

“…6 Lifestyle factors such as smoking, alcohol consumption, body mass index (BMI) and use of aspirin and supplements have been shown to be associated with altered risk of colorectal and endometrial cancer for people with Lynch syndrome. [11][12][13][14][15][16][17][18][19][20][21] There is strong evidence for an inverse association between physical activity and the risk of colorectal cancer for the general population as found by meta-analyses of a large number of studies. [22][23][24][25][26] The most recent evidence from a large pooled-analysis of 12 cohorts that included 1.44 million adults was a reduced risk of both colon and rectal cancers associated with highest levels of leisure-time physical activity compared to lowest levels of physical activity (HR, 0.84; 95% CI, 0.77-0.91 and HR, 0.87; 95% CI, 0.80-0.95 for colon and rectal cancer, respectively).…”

Type 2 diabetes mellitus, blood cholesterol, triglyceride and colorectal cancer risk in Lynch syndrome

“…To minimise bias caused by this non-random ascertainment, we used a "weighted cohort approach" described by Antoniou et al, 20 which has been used in similar studies of modifiers for Lynch syndrome. [21][22][23][24][25][26] Briefly, we first calculated the incidence rates of colorectal cancer for the MMR mutation carriers for age groups <30, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64 and >64 based on colorectal cancer incidence in the general population, averaged for men and women, 27 and the hazard ratio of colorectal cancer for each MMR gene mutated. 9,10,28 These incidence rates was then used together with the number and total person-years of observation for affected and unaffected carriers in each age group to calculate the age-specific sampling fractions.…”