{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:19:54Z","timestamp":1790435994317,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Compromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (<jats:italic>XPC<\/jats:italic>) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR\u2009=\u20091.78, CI\u2009=\u20091.19\u20132.66, p\u2009=\u20090.005); however, Lys939Gln was unrelated (OR\u2009=\u20090.97, CI\u2009=\u20090.65\u20131.45, P\u2009=\u20090.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR\u2009=\u20092.23, CI\u2009=\u20091.28\u20133.87, p\u2009&lt;\u20090.004) or tobacco chewing (OR\u2009=\u20092.40, CI\u2009=\u20091.43\u20134.04, p\u2009=\u20090.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR\u2009=\u20091.54, CI\u2009=\u20091.21\u20131.97, p\u2009=\u20090.001) but not that of Lys939Gln (OR\u2009=\u20091.13, CI\u2009=\u20090.95\u20131.34, p\u2009=\u20090.171) with urinary bladder cancer risk. In conclusion, <jats:italic>XPC<\/jats:italic> Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral.<\/jats:p>","DOI":"10.1038\/srep27018","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T09:57:24Z","timestamp":1464775044000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses"],"prefix":"10.1038","volume":"6","author":[{"given":"Monica","family":"Sankhwar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya Narayan","family":"Sankhwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep Kumar","family":"Bansal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopal","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Singh","family":"Rajender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,1]]},"reference":[{"key":"BFsrep27018_CR1","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1002\/ijc.27949","volume":"132","author":"G Pignot","year":"2013","unstructured":"Pignot, G. et al. MicroRNA expression profile in a large series of bladder tumors: Identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int. J. Cancer 132, 2479\u20132491 (2013).","journal-title":"Int. J. Cancer"},{"key":"BFsrep27018_CR2","doi-asserted-by":"publisher","first-page":"6857","DOI":"10.1158\/0008-5472.CAN-09-1091","volume":"69","author":"MC Stern","year":"2009","unstructured":"Stern, M. C. et al. Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer. Cancer Res. 69, 6857\u20136864 (2009).","journal-title":"Cancer Res."},{"key":"BFsrep27018_CR3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/cncr.26224","volume":"118","author":"J Xing","year":"2012","unstructured":"Xing, J. et al. Comprehensive Pathway-Based Interrogation of Genetic Variations in the Nucleotide Excision DNA Repair Pathway and Risk of Bladder Cancer. Cancer 118, 205\u2013215 (2012).","journal-title":"Cancer"},{"key":"BFsrep27018_CR4","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s11255-009-9560-y","volume":"41","author":"H Wen","year":"2009","unstructured":"Wen, H. et al. Population study of genetic polymorphisms and superficial bladder cancer risk in Han-Chinese smokers in Shanghai. Int. Urol. Nephrol. 41, 855\u2013864 (2009).","journal-title":"Int. Urol. Nephrol."},{"key":"BFsrep27018_CR5","first-page":"31","volume":"46","author":"S Sanyal","year":"2007","unstructured":"Sanyal, S. et al. Polymorphisms in XPD, XPC and the risk of death in patients with urinary bladder neoplasms. ActaOncol. 46, 31\u201341 (2007).","journal-title":"ActaOncol"},{"key":"BFsrep27018_CR6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.mrfmmm.2010.09.003","volume":"694","author":"PJ Verdier","year":"2010","unstructured":"Verdier, P. J. et al. Genotypes, haplotypes and diplotypes of three XPC polymorphisms in urinary-bladder cancer patients. Mutat. Res. 694, 39\u201344 (2010).","journal-title":"Mutat. Res."},{"key":"BFsrep27018_CR7","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1002\/ijc.28089","volume":"133","author":"J He","year":"2013","unstructured":"He, J. et al. Associations of Lys939Gln and Ala499Val polymorphisms of the XPC gene with cancer susceptibility: A meta-analysis. Int. J. Cancer 133, 1765\u20131775 (2013).","journal-title":"Int. J. Cancer"},{"key":"BFsrep27018_CR8","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1038\/sj.bjc.6602616","volume":"92","author":"SC Sak","year":"2005","unstructured":"Sak, S. C. et al. The polyAT, intronic IVS11-6 and Lys939Gln XPC polymorphisms are not associated with transitional cell carcinoma of the bladder. Br. J. Cancer 92, 2262\u20132265 (2005).","journal-title":"Br. J. Cancer"},{"key":"BFsrep27018_CR9","first-page":"3427","volume":"123","author":"Z Xiao-li","year":"2010","unstructured":"Xiao-li, Z. et al. XPC Lys939Gln polymorphism is associated with the decreased response to platinum based chemotherapy in advanced non-small-cell lung cancer. Chinese Medical Journal 123, 3427\u20133432 (2010).","journal-title":"Chinese Medical Journal"},{"key":"BFsrep27018_CR10","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1158\/1055-9965.EPI-06-0288","volume":"15","author":"SC Sak","year":"2006","unstructured":"Sak, S. C., Barrett, J. H., Paul, A. B., Bishop, D. T. & Kiltie, A. E. Comprehensive analysis of 22 XPC polymorphisms and bladder cancer risk. Cancer Epidemiol. Biomarkers Prev. 15, 2537\u20132541 (2006).","journal-title":"Cancer Epidemiol. Biomarkers Prev"},{"key":"BFsrep27018_CR11","first-page":"1853","volume":"28","author":"L Fontana","year":"2008","unstructured":"Fontana, L. et al. DNA Repair Gene ERCC2, XPC, XRCC1, XRCC3 Polymorphisms and associations with bladder cancer risk in a French Cohort. Anticancer Res. 28, 1853\u20131856 (2008).","journal-title":"Anticancer Res."},{"key":"BFsrep27018_CR12","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1093\/carcin\/bgh058","volume":"25","author":"S Sanyal","year":"2004","unstructured":"Sanyal, S. et al. Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis 25, 729\u2013734 (2004).","journal-title":"Carcinogenesis"},{"key":"BFsrep27018_CR13","first-page":"337","volume":"28","author":"Y Liu","year":"2012","unstructured":"Liu, Y. et al. Interactions between cigarette smoking and XPC-PAT genetic polymorphism enhance bladder cancer risk. Oncol. Rep. 28, 337\u2013345 (2012).","journal-title":"Oncol. Rep."},{"key":"BFsrep27018_CR14","doi-asserted-by":"publisher","first-page":"498","DOI":"10.7150\/ijms.4799","volume":"9","author":"Y Zhi","year":"2012","unstructured":"Zhi, Y. et al. Interaction between Polymorphisms of DNA Repair Genes Significantly Modulated Bladder Cancer Risk. Int. J. Med. Sci. 9, 498\u2013505 (2012).","journal-title":"Int. J. Med. Sci."},{"key":"BFsrep27018_CR15","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4103\/0971-6866.96648","volume":"18","author":"RD Mittal","year":"2012","unstructured":"Mittal, R. D. & Mandal, R. K. Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in north Indian population. Ind. J. Hum. Genet. 18, 47\u201355 (2012).","journal-title":"Ind. J. Hum. Genet."},{"key":"BFsrep27018_CR16","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1007\/s00432-009-0717-y","volume":"136","author":"R Gangwar","year":"2010","unstructured":"Gangwar, R., Mandhani, A. & Mittal, R. D. XPC gene variants: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy. J. Cancer Res.Clin. Oncol. 136, 779\u2013786 (2010).","journal-title":"J. Cancer Res.Clin. Oncol."},{"key":"BFsrep27018_CR17","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1086\/500848","volume":"78","author":"X Wu","year":"2006","unstructured":"Wu, X. et al. Bladder Cancer Predisposition: A multigenic approach to DNA-repair and cell-cycle\u2013control genes. Am. J. Hum. Genet. 78, 464\u2013479 (2006).","journal-title":"Am. J. Hum. Genet."},{"key":"BFsrep27018_CR18","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/carcin\/bgl201","volume":"28","author":"Y Zhu","year":"2007","unstructured":"Zhu, Y. et al. Genotypes, haplotypes and diplotypes of XPC and risk of bladder cancer. Carcinogenesis 28, 698\u2013703 (2007).","journal-title":"Carcinogenesis"},{"key":"BFsrep27018_CR19","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1158\/1055-9965.EPI-05-0749","volume":"15","author":"M Garcia-Closas","year":"2006","unstructured":"Garcia-Closas, M. et al. Genetic Variation in the Nucleotide Excision Repair Pathway and Bladder Cancer Risk. Cancer Epidemiol. Biomarkers Prev. 15, 536\u2013542 (2006).","journal-title":"Cancer Epidemiol. Biomarkers Prev"},{"key":"BFsrep27018_CR20","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1093\/carcin\/bgi063","volume":"26","author":"K Broberg","year":"2005","unstructured":"Broberg, K., Bjork, J., Paulsson, K., Hoglund, M. & Albin, M. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis 26, 1263\u20131271 (2005).","journal-title":"Carcinogenesis"},{"key":"BFsrep27018_CR21","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1007\/s12253-011-9398-3","volume":"17","author":"K Rouissi","year":"2011","unstructured":"Rouissi, K. et al. Smoking and polymorphisms in xenobiotic metabolism and DNA repair genes are additive risk factors affecting bladder cancer in Northern Tunisia. Pathol. Oncol. Res. 17, 879\u2013886 (2011).","journal-title":"Pathol. Oncol. Res."},{"key":"BFsrep27018_CR22","doi-asserted-by":"publisher","first-page":"4578","DOI":"10.1158\/0008-5472.CAN-06-0877","volume":"67","author":"Z Chen","year":"2007","unstructured":"Chen, Z. et al. Attenuated expression of xeroderma pigmentosum group C is associated with critical events in human bladder cancer carcinogenesis and progression. Cancer Res. 67, 4578\u20134585 (2007).","journal-title":"Cancer Res."},{"key":"BFsrep27018_CR23","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/ejhg.2008.6","volume":"16","author":"G Francisco","year":"2008","unstructured":"Francisco, G., Menezes, P. R., Eluf-Neto, J. & Chammas, R. XPC polymorphisms play a role in tissue-specific carcinogenesis: a meta-analysis. Eur. J. Hum. Genet. 16, 724\u2013734 (2008).","journal-title":"Eur. J. Hum. Genet."},{"key":"BFsrep27018_CR24","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s10038-007-0215-5","volume":"53","author":"D Zhang","year":"2008","unstructured":"Zhang, D. et al. A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk. J. Hum. Genet. 53, 18\u201333 (2008).","journal-title":"J. Hum. Genet."},{"key":"BFsrep27018_CR25","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1007\/s13277-013-1062-y","volume":"35","author":"QS Dai","year":"2014","unstructured":"Dai, Q. S., Hua, R. X., Zeng, R. F., Long, J. T. & Peng, Z. W. XPC gene polymorphisms contribute to bladder cancer susceptibility: a meta-analysis. Tumour Biol. 35, 447\u2013453 (2014).","journal-title":"Tumour Biol."},{"key":"BFsrep27018_CR26","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/1746-1596-8-112","volume":"8","author":"K Dou","year":"2013","unstructured":"Dou, K., Xu, Q. & Han, X. The association between XPC Lys939Gln gene polymorphism and urinary bladder cancer susceptibility: a systematic review and meta-analysis. Diagn. Pathol. 8, 112 (2013).","journal-title":"Diagn. Pathol"},{"key":"BFsrep27018_CR27","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1007\/s13277-013-1412-9","volume":"35","author":"Y Wang","year":"2014","unstructured":"Wang, Y., Li, Z., Liu, N. & Zhang, G. Association between CCND1 and XPC polymorphisms and bladder cancer risk: a meta-analysis based on 15 case-control studies. Tumour Biol. 35, 3155\u20133165 (2014).","journal-title":"Tumour Biol."},{"key":"BFsrep27018_CR28","unstructured":"Thorlund, K., Engstr\u00f8m, J., Wetterslev, J., Brok, J., Imberger, G. & Gluud, C. User manual for trial sequential analysis (TSA). Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark. 1\u2013115 (2011)."},{"key":"BFsrep27018_CR29","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1093\/ije\/dyn179","volume":"38","author":"K Thorlund","year":"2009","unstructured":"Thorlund, K. et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses\u2009? Int. J. Epidemiol. 38, 276\u2013286 (2009).","journal-title":"Int. J. Epidemiol."},{"key":"BFsrep27018_CR30","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/1471-2288-9-86","volume":"9","author":"J Wetterslev","year":"2009","unstructured":"Wetterslev, J., Thorlund, K., Brok, J. & Gluud, C. Estimating required information size by quantifying diversity in a random-effects meta-analysis. BMC Med. Res. Methodol. 9, 86 (2009).","journal-title":"BMC Med. Res. Methodol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep27018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27018","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T05:13:37Z","timestamp":1672895617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep27018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,1]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,6,29]]}},"alternative-id":["BFsrep27018"],"URL":"https:\/\/doi.org\/10.1038\/srep27018","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,1]]},"assertion":[{"value":"13 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27018"}}