Rama Devi Mittal1, Raju Kumar Mandal, Ruchika Gangwar. 1. Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. ramamittal@gmail.com
Abstract
PURPOSE: Carcinogens causes DNA damage, including oxidative lesions that are removed efficiently by the base excision repair (BER) pathway. Variations in BER genes may reduce DNA repair capacity, leading to development of urological cancers. METHODS: This study included 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 controls who had been frequency matched by age, sex, and ethnicity. We genotyped XRCC1 Exon 6 (C>T), 9 (G>A), 10 (G>A), OGG1 Exon 7 (C>G) and APE1 Exon 5 (T>G) genes polymorphism using PCR-RFLP and ARMS. RESULTS: GA of XRCC1 Exon 9 demonstrated increased risk with PCa as well as in BC (p=0.001; p=0.006). Similarly variant containing genotype revealed association with PCa (p=0.031). Haplotype of XRCC1 also associated with significant risk for PCa and BC. The APE1 GG genotype showed a decreased risk of BC (OR=0.25; p=0.017). Variant genotype GG of OGG1 demonstrated significant risk with BC (p=0.028). CONCLUSIONS: Our observations suggested increased risk for PCa and BC in case of GA genotype for XRCC1, and variant GG in case of OGG1. However APE1 GG genotype conferred a protective association with BC susceptibility. Larger studies and the more SNPs in the same pathway are needed to verify these findings.
PURPOSE: Carcinogens causes DNA damage, including oxidative lesions that are removed efficiently by the base excision repair (BER) pathway. Variations in BER genes may reduce DNA repair capacity, leading to development of urological cancers. METHODS: This study included 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 controls who had been frequency matched by age, sex, and ethnicity. We genotyped XRCC1 Exon 6 (C>T), 9 (G>A), 10 (G>A), OGG1 Exon 7 (C>G) and APE1 Exon 5 (T>G) genes polymorphism using PCR-RFLP and ARMS. RESULTS: GA of XRCC1 Exon 9 demonstrated increased risk with PCa as well as in BC (p=0.001; p=0.006). Similarly variant containing genotype revealed association with PCa (p=0.031). Haplotype of XRCC1 also associated with significant risk for PCa and BC. The APE1 GG genotype showed a decreased risk of BC (OR=0.25; p=0.017). Variant genotype GG of OGG1 demonstrated significant risk with BC (p=0.028). CONCLUSIONS: Our observations suggested increased risk for PCa and BC in case of GA genotype for XRCC1, and variant GG in case of OGG1. However APE1 GG genotype conferred a protective association with BC susceptibility. Larger studies and the more SNPs in the same pathway are needed to verify these findings.