title: TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers.
abstract: Tumor protein p53 (TP53) is the best-known tumor suppressor gene and plays a crucial role in carcinogenesis. The TP53 Arg 72 Pro polymorphism has been reported to be a risk factor for several types of cancer, but its association with pancreatic cancer has not been fully evaluated. Therefore, we investigated the effects of this polymorphism on pancreatic cancer in relation to smoking and drinking habits by examining the distribution of the SNP genotypes in 226 pancreatic cancer patients and 448 healthy controls. The frequencies of Arg/Arg, Arg/Pro and Pro/Pro were found to be 37, 49 and 15% in the pancreatic cancer cases and 44, 46 and 10% in the controls, respectively. Compared to the controls with the Arg/Arg genotype, cases with Pro/Pro homozygosity exhibited a significantly increased risk [adjusted odds ratio (OR)=1.70; 95% confidence interval (CI) 1.01-2.88]. In stratified studies, the association was particularly strong in males (OR=2.62; 95% CI 1.32-5.23), particularly in those smoking in excess of 20 pack-years and drinking in excess of 23 g ethanol/day (OR=5.02; 95% CI 1.12-22.51). We found that the TP53 Pro/Pro genotype compared to the Arg/Arg genotype had a profound effect on pancreatic cancer risk among males, particularly among heavy smokers and excessive alcohol drinkers.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, Okayama 700-8558, Japan. gmd13601@s.okayama-u.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sonoyama
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakai
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Tetsushige
authors.initials: T
authors.lastname: Mimura
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53