Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai. Issue 2 (13th January 2014)

• Record Type: Journal Article
• Authors: Corral, Roman; Lewinger, Juan Pablo; Van Den Berg, David; Joshi, Amit D.; Yuan, Jian‐Min; Gago‐Dominguez, Manuela; Cortessis, Victoria K.; Pike, Malcolm C.; Conti, David V.; Thomas, Duncan C.; Edlund, Christopher K.; Gao, Yu‐Tang; Xiang, Yong‐Bing; Zhang, Wei; Su, Yu‐Chen; Stern, Mariana C.
• Is Part Of: International journal of cancer. Volume 135:Issue 2(2014:Jul. 15)
• Page Start: 335
• Page End: 347
• Publication Date: 2014-01-13
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28693
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1, 004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study, we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repair (BER), nucleotide excision repair (NER), non‐homologous end‐joining (NHEJ) and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and <italic>POLB</italic> rs7832529 (BER) (<italic>p</italic><sub>ACT</sub> = 0.003; <italic>p</italic><sub>pathway</sub> = 0.021) among all, and SNPs in <italic>XPC</italic> (NER) and <italic>OGG1</italic> (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER <italic>p</italic> = 0.034). The <italic>XRCC6</italic> SNP rs2284082 (NHEJ), also in LD with <italic>SREBF2</italic>, showed an interaction with smoking (smoking status interaction <italic>p</italic><sub>gene</sub> = 0.001, <italic>p</italic><sub>pathway</sub> = 0.008, <italic>p</italic><sub>overall</sub> = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (<italic>POLB, OGG1</italic>) and NER genes (<italic>XPC</italic>). A SNP that tags both the <italic>XRCC6</italic> and <italic>SREBF2</italic> genes strongly modifies the association between bladder cancer risk and smoking.</p> </abstract>