Genetic variants of p21 and p27 and pancreatic cancer risk in non-Hispanic Whites: a case-control study.
Genetic variants of p21 and p27 and pancreatic cancer risk in non-Hispanic Whites: a case-control study.
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DOI：
10.1097/mpa.0b013e3181bd51c8
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发表时间：
2010-01
期刊：
影响因子：
2.9
通讯作者：
Frazier ML
中科院分区：
文献类型：
--
作者：
Chen J;Amos CI;Merriman KW;Wei Q;Sen S;Killary AM;Frazier ML
p21 (WAF1/Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members of the Cip/Kip family of cyclin-dependent kinase inhibitors, which can induce cell cycle arrest and serve as tumor suppressors. We hypothesized that genetic variants in p21 and p27 may modify individual susceptibility to pancreatic cancer. To test this hypothesis, we evaluated the associations of the Ser31Arg polymorphism in p21 and the Gly109Val polymorphism in p27, as well as their combinations, with pancreatic cancer risk in a case-control study of 509 pathologically confirmed pancreatic adenocarcinoma patients and 462 age- and sex-matched cancer-free controls in non-Hispanic whites. We found that the heterozygous and homozygous variant genotypes combined in a dominant model of the p21 polymorphism were associated with increased risk of pancreatic cancer compared with the homozygous wild-type (odds ratio [ORadjusted] = 1.70; 95% confidence interval [CI], 1.13–2.55). This increased risk was more pronounced in carriers with the p27 homozygous wild-type (ORadjusted, 2.20; 95% CI, 1.32–3.68) as well as in nonsmokers (ORadjusted, 2.16; 95% CI, 1.14–4.10), although the p27 polymorphism alone was not associated with pancreatic cancer risk. These results indicate that the p21 polymorphism may contribute to susceptibility to pancreatic cancer, particularly among p27 homozygous wild-type carriers and nonsmokers.
