title: Polymorphisms in DNA repair genes XRCC1 and XRCC3, occupational exposure to arsenic and sunlight, and the risk of non-melanoma skin cancer in a European case-control study.
abstract: X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3) polymorphisms are relatively frequent in Caucasian populations and may have implications in skin cancer modulation. A few studies have evaluated their association with non-melanoma skin cancer (NMSC), but the results are inconsistent. In the current study, we aim to assess the impact of XRCC1 R399Q and XRCC3 T241M polymorphisms on the risk of NMSC associated with sunlight and arsenic exposure. Study participants consist of 618 new cases of NMSC and 527 hospital-based controls frequency matched on age, sex, and county of residence from Hungary, Romania, and Slovakia. Adjusted effects are estimated using multivariable logistic regression. The results indicate an increased risk of squamous cell carcinoma (SCC) for the homozygous variant genotype of XRCC1 R399Q (OR 2.53, 95% CI 1.14-5.65) and a protective effect against basal cell carcinoma (BCC) for the homozygous variant genotype of XRCC3 T241M (OR 0.61, 95% CI 0.41-0.92), compared with the respective homozygous common genotypes. Significant interactions are detected between XRCC3 T241M and sunlight exposure at work, and between XRCC3 T241M and exposure to arsenic in drinking water (p-value for interaction <0.10). In conclusion, the current study demonstrates that polymorphisms in XRCC genes may modify the associations between skin cancer risk and exposure to sunlight or arsenic. Given the high prevalence of genetic polymorphisms modifying the association between exposure to environmental carcinogens and NMSC, these results are of substantial relevance to public health.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, 1 University Place, Rensselaer, NY 12144, USA; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, USA; Institute for Health and the Environment, University at Albany, State University of New York, Rensselaer, NY, USA. Electronic address: ssurdu@albany.edu.
authors.forename: Simona
authors.initials: S
authors.lastname: Surdu
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, 1 University Place, Rensselaer, NY 12144, USA; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, USA.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Fitzgerald
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, 1 University Place, Rensselaer, NY 12144, USA; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, USA; Institute for Health and the Environment, University at Albany, State University of New York, Rensselaer, NY, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bloom
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, USA; New York State Cancer Registry, New York State Department of Health, Albany, NY, USA.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Boscoe
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, 1 University Place, Rensselaer, NY 12144, USA; Institute for Health and the Environment, University at Albany, State University of New York, Rensselaer, NY, USA.
authors.forename: David O
authors.initials: DO
authors.lastname: Carpenter
authors.affiliation: Institute for Health and the Environment, University at Albany, State University of New York, Rensselaer, NY, USA; Department of Educational and Counseling Psychology, School of Education, University at Albany, State University of New York, Albany, NY, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Haase
authors.affiliation: Health Department, Environmental Health Center, Cluj-Napoca, Romania.
authors.forename: Eugen
authors.initials: E
authors.lastname: Gurzau
authors.affiliation: Department of Environmental Epidemiology, National Institute of Environmental Health, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.affiliation: Department of Environmental Health, Regional Authority of Public Health, Banska Bystrica, Slovakia.
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Koppova
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Vahter
authors.affiliation: Department of Social and Environmental Health Research, Public Health, London School of Hygiene and Tropical Medicine, London, UK; Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, UK.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Leonardi
authors.affiliation: Institut für Chemie-Analytische Chemie, Karl-Franzens-Universität, Graz, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Goessler
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Social and Environmental Health Research, Public Health, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Fletcher
mesh_terms: D000368:Aged; D001151:Arsenic / Q000633:toxicity*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012878:Skin Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology; D013472:Sunlight
chemical_list: D001151:Arsenic
keywords: Arsenic; DNA repair polymorphisms; Exposure; Non-melanoma skin cancer; Sunlight