Abstract
BackgroundThe risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas.MethodsWe used a case-control study design (156 carcinomas, 981 adenomas and 399 controls) to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (CI) were estimated by binary logistic regression model adjusting for age and gender.ResultsThe ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06–1.81), which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15–2.39). The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49–1.01) and carcinomas (OR of 0.49, 95% CI 0.21–1.13) among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95–5.04) compared to all non-carriers although the estimate was not statistically significant.ConclusionWe found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women.
Highlights
The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance
Genetic variants represented by single nucleotide polymorphisms (SNPs) in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to Colorectal cancer (CRC)
The genotype distributions for the studied polymorphisms were all in Hardy-Weinberg equilibrium (ERCC1 Asn118Asn p = 0.945, ASE-1 G-21A p = 0.757 and RAI IVS1 A4364G p = 0.673), and the distributions of the alleles are in agreement with those found in other Scandinavian populations [7,8]
Summary
The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. Genetic variants represented by single nucleotide polymorphisms (SNPs) in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to CRC. A region in chromosome 19q13.2-3 encompassing the genes ERCC1, ASE-1 and RAI was identified as a high-risk haplotype, defined as homozygous carriers of a haplotype consisting of ERCC1 Asn118AsnA, ASE-1 G-21AG and RAI IVS1 A4364GA This haplotype consisting of three marker SNPs, is shown to be strongly associated with increased risk of skin cancer [5], breast cancer [6] and lung cancer [7] when compared to persons that are not homozygous carriers of the haplotype. The region of chromosome 19 seems to be involved in the balance between growth and elimination of DNA damage and unwanted cells [8]
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