Variant genotypes of CDKN1A and CDKN1B are associated with an increased risk of breast cancer in Chinese women

Abstract

p21Cip1 and p27 Kip1 are cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumor suppressors. Reduced protein expression of p21Cip1 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 C120T in CDKN1A and C279T 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 C279T [adjusted OR 5 1.43 (95% CI 5 1.0321.98) for 279TC/ TT], compared with the 279CC 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 5 1.49, 95% CI 5 1.1122.01 among subjects carrying 3 or more variant alleles), especially among premenopausal women (adjusted OR5 2.30, 95% CI 5 1.4523.66). 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. ' 2006 Wiley-Liss, Inc.

p27Kip1 V109G Polymorphism and Cancer Risk: A Systematic Review and Meta-Analysis

“…Among these, 11 publications appeared to meet the inclusion criteria and were subjected to a detailed full-text review. [12][13][14][15][16][17][18][19][20][21][22] We further excluded three publications because they did not provide detailed genotype data of cases and controls. 18,20,22 Therefore, our final data pooling consisted of eight publications (Table 1).…”

“…18,20,22 Therefore, our final data pooling consisted of eight publications (Table 1). [12][13][14][15][16][17]19,21 Three of the eight case-control studies were conducted in Caucasians, and the remaining five studies were conducted in Asians. Overall, there were four breast cancer studies, two prostate cancer studies, one pancreatic cancer study, and one oral squamous cell cancer study.…”

“…China. between the p27V109G polymorphism and breast cancer risk, [15][16][17][18] pancreatic cancer risk, 19,20 prostate cancer risk, 21 and thyroid cancer risk. 22 To investigate whether the p27V109G variant is indeed associated with cancer susceptibility, we performed a systematic review of the published articles, and conducted a meta-analysis to gain insights into the relationship between the p27V109G polymorphism and cancer risk.…”

Lack of Association of BRCA1 and BRCA2 Variants with Breast Cancer in an Ethnic Population of Saudi Arabia, an Emerging High-Risk Area

“…The risk of breast cancer is raised about two fold in the affected Saudi women. Several studies have identified an association with SNPs and breast cancer in the Chinese population (Ma et al, 2006). It has been proposed that different genetic backgrounds due to the combination of environmental could explain the remaining familial breast cancer risk (Pharoah et al, 2002).…”

Low penetrance breast cancer predisposition SNPs are site specific

“…SNPs on 2q35 (rs13387042) and 5p12 (rs4415084 and rs10941679) have been shown to be associated with estrogen-receptor (ER) positive breast cancer [5,6] and SNPs lying within cell cycle genes have been shown to be associated with breast cancer in the British population (rs997669 in CCNE1, rs3176336 in CDKN1A, rs34330 in CDKN1B and rs3731239 in CDKN2A/2B) [7]. These associations have yet to be confirmed in other studies or populations, with the exception of rs34330, which has been shown to be associated with breast cancer in the Chinese population [8].…”