Elsevier

Surgery

Volume 149, Issue 1, January 2011, Pages 126-134
Surgery

Original Communication
Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for urinary bladder cancer in North India

https://doi.org/10.1016/j.surg.2010.04.004Get rights and content

Background

Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes that are relevant to cancer development. It is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. The gene for COX-2, designated as prostaglandin-endoperoxide synthase 2 (PTGS-2), carries polymorphisms, such as -765G>C, 1195G>A in the promoter region, and 8473T>C in the 3'-untranslated region (UTR), which have been associated with susceptibility to malignant disease.

Methods

We undertook a case-control study of 212 urothelial bladder cancer (UBC) cases and 250 controls to investigate the association between COX-2 polymorphism and bladder cancer susceptibility, using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated gene–environment interactions.

Results

Cox-2 765G>C, a variant(C) allele carrier, was at an increased risk of UBC (odds ratio [OR] = 1.90; P = .004); however, –1195G>A; –1290A>G; and 3'UTR 8473T>C polymorphisms of COX-2 gene were not significantly associated with UBC. 765G>C also was associated with the invasive stage of a bladder tumor (OR = 2.73; P = .033). High risk for UBC also was observed with respect to COX-2 haplotypes C-765T8473A-1195A-1290 (OR = 3.47; P = .014). In case-only analysis, COX-2 765 variant allele carrier genotypes also showed an increased risk among former and current smokers (OR = 3.06; P = .041 and OR = 4.39; P = .032, respectively).

Conclusion

COX-2 -765G>C polymorphism confers UBC susceptibility particularly in smokers and in patients with invasive tumors. 765C allele carrier genotypes also are influenced with a high risk of recurrence in Bacillus Calmette-Guérin-treated patients. Collectively, these findings confirm that the COX-2 -765G>C polymorphism is a risk factor for the development of bladder cancer and can provide a plausible mechanistic explanation. Further validation in large population-based studies is needed.

Section snippets

Materials and methods

We conducted a group-matched case-control study. The participants in this study were unrelated, North Indian individuals from Lucknow and other adjoining cities of north India visiting the Department of Urology at Sanjay Gandhi Postgraduate Institute of Medical Sciences, a tertiary care center, between May 2004 and June 2009. Our study included 212 histologically confirmed transitional urothelial bladder cancer patients with a mean age of 58.5 years and a male-to-female (M/F) ratio of 187:25.

Characteristics of subjects

A total of 250 controls and 212 cases were recruited for this study. No significant age difference was noted between the cases (58.5 ± 12.4 years) and the controls (56. 8 ± 10.8 years; P = .107). The cases had a significantly higher percentage of smokers (57.4%) than the controls (30.8%; P = .001). The demographic details of the study subjects and the clinical characteristics of the patients are presented in Table I.

Cox-2 gene polymorphisms in bladder cancer

The genotype and allele frequencies of the COX-2 gene polymorphism in healthy

Discussion

COX-2 is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors. In this study, we aimed to investigate the role of COX-2 –765G>C, –1195G>A, –1290G>A, and 8473T>C 3'UTR polymorphisms in a case-control study in a north Indian population. Using the dominant mode model, we found that only –765C allele carriers were significantly associated with a risk of UBC. The risk was increased by an invasive tumor. The gene environment interaction revealed the association between

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Supported by a grant from the Department of Science and Technology, New Delhi Government of India.

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