TY - JOUR
T1 - Variant genotypes of CDKN1A and CDKN1B are associated with an increased risk of breast cancer in Chinese women
AU - Ma, Hongxia
AU - Jin, Guangfu
AU - Hu, Zhibin
AU - Zhai, Xiangjun
AU - Chen, Wensen
AU - Wang, Shui
AU - Wang, Xuechen
AU - Qin, Jianwei
AU - Gao, Jun
AU - Liu, Jiyong
AU - Wang, Xinru
AU - Wei, Qingyi
AU - Shen, Hongbing
PY - 2006/11/1
Y1 - 2006/11/1
N2 - 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 in CDKN1A (encode for p21 Cip1) and CDKN1B (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 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.
AB - 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 in CDKN1A (encode for p21 Cip1) and CDKN1B (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 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.
KW - Breast cancer
KW - CDKN1A
KW - CDKN1B
KW - Genetic polymorphisms
KW - Molecular epidemiology
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U2 - 10.1002/ijc.22094
DO - 10.1002/ijc.22094
M3 - Article
C2 - 16804901
AN - SCOPUS:33748854758
SN - 0020-7136
VL - 119
SP - 2173
EP - 2178
JO - International journal of cancer
JF - International journal of cancer
IS - 9
ER -