Genetic variants of p21 and p27 and pancreatic cancer risk in non-Hispanic Whites: a case-control study.
OBJECTIVE
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.


METHODS
To test this hypothesis, we evaluated the associations of the Ser31Arg polymorphism in p21 and the Gly109Val polymorphism in p27, and 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.


RESULTS
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 (adjusted 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) and in nonsmokers (ORadjusted, 2.16; 95% CI, 1.14-4.10), although the p27 polymorphism alone was not associated with pancreatic cancer risk.


CONCLUSIONS
These results indicate that the p21 polymorphism may contribute to susceptibility to pancreatic cancer, particularly among p27 homozygous wild-type carriers and nonsmokers.
Chen
Jinyun
J
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Amos
Christopher I
CI
Merriman
Kelly W
KW
Wei
Qingyi
Q
Sen
Subrata
S
Killary
Ann M
AM
Frazier
Marsha L
ML
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking; D044465:White People / Q000235:genetics*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27