Genetic variants of p21 and p27 and hepatocellular cancer risk in a Chinese Han population: A case‐control study

• Published in: International journal of cancer Vol. 132; no. 9; pp. 2056 - 2064
• Main Authors: Liu, Fei, Wei, Yong‐Gang, Luo, Li‐Mei, Wang, Wen‐Tao, Yan, Lv‐Nan, Wen, Tian‐Fu, Xu, Ming‐Qing, Yang, Jia‐Yin, Li, Bo
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2013; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Arrests; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Cancer; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - etiology; Carcinoma, Hepatocellular - pathology; Case-Control Studies; case–control study; CDKN1A; CDKN1B; Cell growth; China - epidemiology; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Cyclin-dependent kinases; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetic diversity; Genetic Predisposition to Disease; Genotype; hepatocellular carcinoma susceptibility; Humans; Kinases; Liver cancer; Liver Neoplasms - epidemiology; Liver Neoplasms - etiology; Liver Neoplasms - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical research; Medical sciences; Middle Aged; Polymorphism; Polymorphism, Genetic - genetics; Prognosis; Proteins; Risk Factors; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumors; Asia; China; KIP1 Gene; CDKN1A; Genetic variability; CDKN1B; CDKN1A Gene; Hepatic disease; Hepatocellular carcinoma; Risk; Case control study; Epidemiology; Liver cancer; Cancerology; case-control study; Predisposition; Public health; hepatocellular carcinoma susceptibility; Tumor suppressor gene; Human; Genetic variant; Genotype; Malignant tumor; Sensitivity; Risk factor; Digestive diseases; Cancer; Polymorphism
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.27885

The p21 (Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members of the Cip/Kip family of cyclin‐dependent kinase inhibitors, which can arrest cell proliferation and serve as tumour suppressors. We hypothesized that genetic variants in p21 and p27 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T in p21 and C‐79T and Gly109Val in p27, as well as their combinations, with HCC risk in a case‐control study of 476 HCC cases and 526 cancer‐free controls in a Chinese population. The matrix‐assisted laser desorption ionisation time‐of‐flight (MALDI‐TOF) mass spectrometry method was performed to detect these polymorphisms. We found that the variant genotypes of p21 Ser31Arg and p27 C‐79T were individually associated with a significantly increased risk of HCC, but no associations were observed for other variant genotypes. Moreover, the combined variant genotypes of the four loci were associated with a significantly increased HCC risk (adjusted OR = 2.24, 95% CI = 1.72, 2.91 among subjects carrying 3 or more variant alleles), especially among HbsAg‐positive individuals (adjusted OR = 3.09, 95% CI = 1.86, 5.14). Furthermore, the combined variant genotypes of the four loci (carrying three or more variant alleles) increased a 1.93‐fold (95% CI = 1.20, 3.09) and 1.76‐fold (95% CI = 1.17, 2.64) risk of HCC among smokers and nonsmokers. The variant genotypes of the two genes in this study have negative correlation with the clinicopathologicals observed. These results suggest that p21 polymorphisms individually or in combination with p27 polymorphisms increases risk of HCC, particularly among HbsAg‐positive individuals. What's new? Cell‐cycle control proteins p21 and p27 can arrest cell proliferation, but alterations in these proteins could lead to cancer. In this study, the authors investigated whether individual variation in p21 and p27 contribute to risk of liver cancer in a Chinese population. By conducting a case‐control study, they detected that certain p21 polymorphisms, either alone or in conjunction with p27 variants, can increase risk of hepatocellular carcinoma.