Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer risk.

It has been well elucidated that the signal transduction of cell-cycle control pathway and apoptosis pathway plays an important role in the normal growth and differentiation of organisms. To test the hypothesis that mutants of key genes involved in cell-cycle regulation and apoptosis might contribute to the increased risk of colorectal cancer (CRC), a population-based case-control study was carried out in Jiashan County, Zhejiang Province. The study population was composed of 373 CRC cases and 838 controls. Five genetic variants including CCND1 G870A, p21 codon31 C/A, p21 3'UTR C/T, caspase8 IVS12-19G/A, and caspase8 6n del/ins were genotyped. The associations of the polymorphisms with CRC were estimated by logistical regression model after adjustment for the important covariates. The interactive effect among the five selected genetic polymorphisms on CRC was explored by multifactor dimensionality reduction (MDR) software. The significant association between five single-nucleotide polymorphisms (SNPs) and CRC risk was not observed, respectively. However, caspase8 del/del showed a marginally significant association with the increased risk of rectum cancer [adjusted odds ratio (OR) (95% confidence interval, CI) = 1.92 (0.97-3.79); P = 0.06]. Furthermore, the MDR analysis indicated that the best interactive model for CRC included three factors-CCND1 G870A, caspase8 IVS12-19G/A, and caspase8 6 n del/ins-with 53.44% testing balanced accuracy and 10/10 cross-validation consistency, but the model was no longer significant after the 1000 times permutation test (P = 0.25). Our findings suggest that the selected polymorphisms of p21, CCND1, and caspase8 may not contribute to the risk of colorectal cancer. 2009 Wiley-Liss, Inc.