The association of cyclin D1 G870A and E-cadherin C-160A polymorphisms with the risk of colorectal cancer in a case control study and meta-analysis.

Cyclin D1 (CCND1) and E-cadherin (CDH1) have been shown to be important genes of the beta-catenin/LEF pathway that is involved in colorectal carcinogenesis. However, epidemiological studies on relationship between genetic variants of these two genes and colorectal cancer (CRC) have shown inconsistent results. In a population-based case-control study (498 cases and 600 controls), we assessed the association of CCND1 G870A and CDH1 C-160A polymorphisms with CRC risk. Multivariable logistic regression analysis was used to estimate the association between genotypes, environmental exposures and CRC risk, adjusting for potential confounders. Compared to common homozygotes, the OR for heterozygous and homozygote variant genotype was 1.08 (95% CI, 0.80-1.46) in CCND1 and 0.97 (95% CI, 0.75-1.25) in CDH1. Neither tumor stage nor location showed an association with genetic susceptibility. However, a significant interaction between hormone replacement therapy (HRT) and CCND1 genotypes in CRC risk was found among postmenopausal women (p(interaction) = 0.02). The risk reduction associated with HRT was substantial (OR, 0.09; 95% CI, 0.02-0.35) in women who were GG homozygous. A meta-analyses including 11 published studies on CCND1 G870A in addition to our study showed a slightly increased risk of CRC for carriers of the A allele (OR, 1.19; 95% CI, 1.06-1.34); however, there was some indication of publication bias. We conclude that the CCND1 G870A and CDH1 C-160A polymorphisms are not associated with the risk of CRC in the German population. However, the CCND1 G870A polymorphism may modify the protective effect of postmenopausal hormone use on the development of CRC.