Abstract
The association between alcohol intake and colorectal cancer (CRC) may vary secondary to single nucleotide polymorphisms (SNPs) in two pathways related to alcohol intake. 375 cases of CRC were identified among 38 373 Japan Public Health Center-based prospective Study (JPHC Study) participants who had returned a baseline questionnaire, reported no diagnosis of any cancer and provided blood samples. For each case, two controls were selected on matching variables. Logistic regression models were used to determine matched Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between alcohol consumption, genetic polymorphisms of enzymes in the alcohol- and folate metabolic pathways (e.g. methylenetetrahydrofolate reductase (MTHFR) rs1801133) and CRC risk. Compared to never/occasional alcohol intake, moderate to heavy alcohol intake was associated with CRC (OR = 2.12, 95% CI, 1.34–3.36). When compared to the CC genotype, the MTHFR rs1801133 CT/TT genotype was inversely associated with CRC (OR = 0.72, 95% CI, 0.54–0.97). Never/occasional consumers of alcohol with the MTHFR rs1801133 CT/TT genotype were also at a reduced risk of CRC compared to never/occasional drinkers with the CC genotype (OR = 0.68, 95% CI, 0.47–0.98) (P for interaction = 0.27). The results indicate that the folate pathway is likely to be involved in alcohol-related CRC development.
Highlights
Matching value Matching value interaction with alcohol consumption
Alcohol intake was positively associated with colorectal cancer in both the minimally (OR = 1.66, 95% Confidence Intervals (CI), 1.10–2.51) and fully adjusted conditional models (OR = 2.12, 95% CI, 1.34–3.36) (Table 2)
The inverse association was significant in individuals with the MTHFR rs1801133 CT genotype (OR = 0.66, 95% CI, 0.48–0.91), while non-significant in those with the MTHFR rs1801133 TT genotype (OR = 0.87, 95% CI, 0.58–1.30)
Summary
The aim of the current study was to investigate the effect of gene-alcohol interactions on CRC risk using a nested case-control study within the Japan Public Health Center-based prospective Study (JPHC Study)
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