Colorectal Cancer Risk Variants Research Articles

No Evidence for Variation in Colorectal Cancer Risk Associated With Different Types of Postmenopausal Hormone Therapy

Little is known about the effects of various types, modes, and routes of hormone replacement therapy (HRT) on the risk of colorectal cancer (CRC) among postmenopausal women. We conducted a population-based case-control study with validation of self-reported hormone use and no upper age limit. In 1,456 postmenopausal women aged 45-94 years (546 cases, 910 controls), the use of HRT was associated with reduction in CRC risk among ever users (adjusted odds ratio (OR) 0.65, 95% confidence interval 0.50-0.84), current users, and recent users. There was no evidence that risk reduction among current users varies by age. Risk reduction was seen both in estrogen-only therapy (0.42, 0.23-0.78) and in combination therapy (0.60, 0.41-0.87), the latter regardless of the mode of therapy, whether with hormone patches (0.40, 0.17-0.90) or with oral tablets (0.59, 0.39-0.90). In combination with estrogen, progestagens of the norethisterone and levonorgestrel families were associated with strong reduction in CRC risk.

Aurora‐A and Cyclin D1 polymorphisms and the age of onset of colorectal cancer in hereditary nonpolyposis colorectal cancer

Polymorphisms in the 2 cell-cycle control genes Aurora A and Cyclin D1 have previously been associated with changes in the age of onset of colorectal cancer in persons harboring germline mutations in DNA mismatch repair genes associated with hereditary nonpolyposis colorectal cancer (HNPCC). In this report, we have genotyped 312 individuals, who all harbored confirmed causative mutations in either hMSH2 or hMLH1, for 2 polymorphisms, one in Aurora A (T91A) and the other in Cyclin D1 (G870A). The results reveal that the previous association with the Aurora A polymorphism could not be confirmed in our larger group of HNPCC patients. The Cyclin D1 polymorphism, however, was associated with a significant difference in the age of disease onset on patients harboring hMSH2 mutations, which was not observed in hMLH1 mutation carriers. A combined analysis of the Aurora A and Cyclin D1 polymorphisms did not reveal any obvious association. In conclusion, it appears that the polymorphic variant of Aurora A does not appear to be associated with variation in colorectal cancer risk in HNPCC, whereas there is a more complex relationship between the Cyclin D1 polymorphism and disease risk in HNPCC.

A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk

To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant (P(trend) = 1.0 x 10(-12)).