Variant genotypes ofCDKN1AandCDKN1Bare associated with an increased risk of breast cancer in Chinese women


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Abstract

p21Cip1 and p27Kip1 are cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumor suppressors. Reduced protein expression of p21Cip1 and p27Kip1 was frequently observed in a subset of cancers, including breast cancer. In this study, we hypothesized that genetic variants inCDKN1A(encode for p21Cip1) andCDKN1B(encode for p27Kip1) may modulate the risk of breast cancer. To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T inCDKN1Aand C−79T and Gly109Val inCDKN1B, as well as their combinations, with breast cancer risk in a case-control study of 368 breast cancer cases and 467 cancer-free controls in a Chinese population. We found that a significantly increased risk of breast cancer was associated with the variant genotypes ofCDKN1BC−79T [adjusted OR = 1.43 (95% CI = 1.03−1.98) for −79TC/TT], compared with the −79CC genotype, but no associations were observed for other variant genotypes. However, the combined variant genotypes of the 4 loci were associated with a significantly increased breast cancer risk (adjusted OR = 1.49, 95% CI = 1.11−2.01 among subjects carrying 3 or more variant alleles), especially among premenopausal women (adjusted OR= 2.30, 95% CI = 1.45−3.66). Furthermore, in premenopausal women, this significant association remained unchanged, after including other individual risk factors in the multivariate logistic regression model, suggesting an independent role ofCDKN1AandCDKN1Bvariants in breast cancer risk. Although the exact biological mechanism remains to be explored, our findings suggest possible involvement ofCDKN1AandCDKN1Bvariants in the etiology of breast cancer. Further large and functional studies are needed to confirm our findings.

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