title: Variant genotypes of CDKN1A and CDKN1B are associated with an increased risk of breast cancer in Chinese women.
abstract: p21(Cip1) and p27(Kip1) are cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumor suppressors. Reduced protein expression of p21(Cip1) and p27(Kip1) was frequently observed in a subset of cancers, including breast cancer. In this study, we hypothesized that genetic variants in CDKN1A (encode for p21(Cip1)) and CDKN1B (encode for p27(Kip1)) may modulate the risk of breast cancer. To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T in CDKN1A and C-79T and Gly109Val in CDKN1B, 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 of CDKN1B C-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 of CDKN1A and CDKN1B variants in breast cancer risk. Although the exact biological mechanism remains to be explored, our findings suggest possible involvement of CDKN1A and CDKN1B variants in the etiology of breast cancer. Further large and functional studies are needed to confirm our findings.
authors.affiliation: Laboratory of Reproductive Medicine and Applied Toxicology, Nanjing Medical University, Nanjing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhai
authors.forename: Wensen
authors.initials: W
authors.lastname: Chen
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
authors.forename: Xuechen
authors.initials: X
authors.lastname: Wang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Qin
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017931:DNA Primers; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008593:Menopause; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27