Abstract
BackgroundMore than 50% of the colorectal cancer (CRC) etiology has been attributed to diet. Established or suspected dietary factors modifying risk of CRC are red meat, cereals, fish, and fibre. Diet and lifestyle may be linked to cancer through inflammation. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. We wanted to test if dietary factors and IL10 polymorphisms interact in relation to colorectal carcinogenesis.MethodsThe functional IL10 polymorphism C-592A (rs1800872) and the marker rs3024505 were assessed in relation to diet and lifestyle in a nested case-cohort study of 378 CRC cases and 775 randomly selected participants from a prospective study of 57,053 persons. Genotyping data on the IL10 polymorphism C-592A, smoking and non-steroidal anti-inflammatory drugs (NSAID) was retrieved from Vogel et al. (Mutat Res, 2007; 624:88). Incidence rate ratios (IRR) and 95% Confidence Interval (95% CI) were calculated.ResultsNo associations were found between the IL10 rs3024505 polymorphism and risk of CRC. There was interaction between rs3024505 and dietary fibre (P-value for interaction = 0.01). IL10 rs3024505 homozygous wildtype carriers were at 27% reduced risk of CRC per 10 g fibre per day (95% CI: 0.60-0.88) whereas variant carriers had no risk reduction by fibre intake. Also, interaction between IL10 C-592A and intake of fibre was found (P-value for interaction = 0.02). Among those eating <17.0 grams of fibre per day, carriers of an C-592A variant allele had a statistically significantly higher risk of colorectal cancer compared to homozygous wildtypes. No significant differences in colorectal cancer risk were observed between the reference group (CC and <17.0 g/day) and carriers of one C-592A variant allele eating 17.0 or more grams of dietary fibre per day. This suggests that the increased risk due to carrying the variant allele can be overcome by higher fibre intake. No interactions between IL10 polymorphisms and dietary meat, cereal, or fish intake, or between IL10 rs3024505 and smoking or NSAID use were found.ConclusionsIn this northern Caucasian cohort we found interaction between IL10 and dietary fibre in CRC carcinogenesis. High intake of fibre seems to protect against CRC among individuals with IL10 related genetic susceptibility to CRC. This finding should be evaluated in other prospective and population-based cohorts with different ethnic groups.
Highlights
More than 50% of the colorectal cancer (CRC) etiology has been attributed to diet
The genotype distribution of the polymorphisms in the subcohort did not deviate from Hardy-Weinberg equilibrium
Associations between polymorphisms and CRC There was no association between IL10 rs3024505 genotypes and CRC risk (Table 2)
Summary
More than 50% of the colorectal cancer (CRC) etiology has been attributed to diet. Established or suspected dietary factors modifying risk of CRC are red meat, cereals, fish, and fibre. More than 50% of the CRC etiology has been attributed to diet and lifestyle [1,3] and, may be potentially avoidable by modification of these factors [4]. A modified inflammatory response may be an intermediate between diet and lifestyle on one hand and CRC on the other. Suspected dietary risk factors for CRC are red meat, dietary fibre, cereals and fish [4,5]. Dietary fibre were found to protect against CRC (adjusted relative risk 0.75 (95% CI: 0.59-0.95) for the highest versus lowest quintile of intake) [5]. Long term use of non-steroidal anti-inflammatory drugs (NSAID) has been found to confer protection against CRC presumably by lowering an inflammatory response in colon [16,17]
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