Functional polymorphisms of the cyclooxygenase (PTGS2) gene and risk for gallbladder cancer in a North Indian population

• Published in: Journal of gastroenterology 2009-07, Vol.44 (7), p.774-780
• Main Authors: Srivastava, Kshitij, Srivastava, Anvesha, Pandey, Sachchida Nand, Kumar, Ashok, Mittal, Balraj
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Biliary Tract; Case-Control Studies; Colorectal Surgery; Cyclooxygenase 2 - genetics; Female; Gallbladder Neoplasms - genetics; Gastroenterology; Genetic Predisposition to Disease; Genotype; Hepatology; Humans; India; Male; Medicine; Medicine & Public Health; Middle Aged; Original Article—Liver; Pancreas; Polymorphism, Genetic; Risk; Surgical Oncology
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-009-0071-5

Background Cyclooxygenase-2 ( PTGS2 ) overexpression has been implicated in various cancers. We aimed to evaluate the role of PTGS2 −1195G>A [reference sequence (rs) 689466], −765G>C (rs20417) and +8473T>C (rs5275) polymorphisms in conferring interindividual susceptibility to gallbladder cancer. Materials and methods The study included 167 gallbladder cancer cases and 184 controls. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Risk was estimated using unconditional logistic regression. Results Significant risk was observed in the presence of PTGS2 −1195GA ( P  = 0.006; odds ratio = 2.00; 95% confidence interval = 1.2–3.3) and AA genotypes ( P  = 0.050; odds ratio = 2.98; 95% confidence interval = 1.0–8.9). Combined risk due to GA + AA genotypes was 2.12 ( P  = 0.002; 95% confidence interval = 1.3–3.3; P -trend = 0.001). Sub-grouping showed a risk due to the PTGS2 −1195(GA + AA) genotype in males ( P  = 0.007; odds ratio = 2.97; 95% confidence interval = 1.3–6.5), patients without gallstones ( P  = 0.001; odds ratio = 2.53; 95% confidence interval = 1.4–4.7) and with late-onset gallbladder cancer ( P  = 0.012; odds ratio = 1.99; 95% confidence interval = 1.1–3.4). Gallbladder cancer patients who used tobacco were at increased risk in the presence of the PTGS2 −765GC genotype ( P  = 0.018; odds ratio = 2.96; 95% confidence interval = 1.2–7.2). Discussion An association of PTGS2 −1195G>A polymorphism with gallbladder cancer, particularly in patients without gallstones, suggests a direct role of PTGS2 in cancer development.