Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin

Carcinogenesis, Aug 2006

In addition to environmental exposures like UV radiation and, in some cases, arsenic contamination of drinking water, genetic factors may also influence the individual susceptibility to basal cell carcinoma of skin (BCC). In the present study, 529 cases diagnosed with BCC and 533 controls from Hungary, Romania and Slovakia were genotyped for one polymorphism in each of seven DNA repair genes. The variant allele for T241M (C>T) polymorphism in the XRCC3 gene was associated with a decreased cancer risk [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.61–0.88; P = 0.0007, multiple testing corrected P = 0.004]. The risk of multiple BCC was significantly lower among variant allele carriers than in non-carriers (P = 0.04). Men homozygous for the C-allele for E185Q (G>C) polymorphism in the NBS1 gene showed an increased BCC risk (OR, 2.19; 95% CI, 1.23–3.91), but not women (OR, 0.84; 95% CI, 0.49–1.47). In men, the age and nationality adjusted OR for the genotype CC (XRCC3)/CC (NBS1) was 8.79 (95% CI, 2.10–36.8), compared with the genotype TT (XRCC3)/GG (NBS1). The data from this study show overall risk modulation of BCC by variant allele for T241M polymorphism in XRCC3 and gender-specific effect by E185Q polymorphism in NBS1.

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Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin

Ranjit Kumar Thirumaran 2 Justo Lorenzo Bermejo 2 Peter Rudnai 1 Eugene Gurzau 0 Kvetoslava Koppova 6 Walter Goessler 5 Marie Vahter 4 Giovanni S.Leonardi 3 Felicity Clemens 3 Tony Fletcher 3 Kari Hemminki 2 7 Rajiv Kumar 2 7 0 Environmental Health Center , Cluj, Romania 1 National Institute of Environmental Health , Budapest, Hungary 2 Division of Molecular Genetic Epidemiology, German Cancer Research Center , Im Neuenheimer Feld 580, 69120 Heidelberg, Germany 3 London School of Hygiene and Tropical Medicine , London, UK 4 Institute of Environmental Medicine, Karolinska Institute , Stockholm, Sweden 5 Institute for Chemistry, Karl-Franzens University , Graz, Austria 6 State Health Institute , Banska Bystrica, Slovakia 7 Department of Biosciences at Novum, Karolinska Institute , Huddinge, Sweden To whom correspondence should be addressed Email: # The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: 1676 Introduction These authors contributed equally to this work. Materials and methods Direct DNA sequencing Statistical analysis to inconsistency of the current data on the functional effects of the studied polymorphisms, all tests applied were two-sided. Results Cases (with BCC) Controls 95% CI Discussion a d ( XRCC3 Genotype XRCC3 genotype Multiple BCCb N2 OR 95% CI 229 39 1 236 32 0.86 64 8 0.89 130 22 1 124 15 0.82 38 4 0.78 64 0.501.48 0.86 66 0.382.11 68 65 0.401.89 0.92 67 0.303.75 70 64 0.381.76 0.85 66 0.232.58 68 Age at onset of BCC Median 5th and 95th Pc percentiles 41, 78 44, 78 45, 77 41, 78 43, 79 49, 78 41, 78 44, 76 44, 77 aN1 is the number of BCC cases and N2 is the number of cases with multiple BCCs. bAdjusted for age, sex and nationality. cP-values from KruskalWallis tests. NBS1 Genotype Age and nationality standardized ORs ORa (Carriers versus non-carriers) Complexion Light Medium Effect of sun on skin Blistered/burnt 0.66 Mild burn 0.74 Tan 0.78 95% CI Median age of onset Non-carriers Carriers 0.420.92 0.18c 0.471.01 aORs and 95% CIs were adjusted for gender, nationality and age (as a continuous variable), complexion and effect of sun on skin. bP-values from MannWhitney tests. cInteraction XRCC3 carrier status complexion. dInteraction XRCC3 carrier status effect of sun on skin. material are available at Carcinogenesis Supplementary material Supplementary Online Acknowledgements We acknowledge the technical assistance by Ms Dagmar Beisse. This study was supported by an EU grant within ASHRAM project QLK4-CT-200100264. Conflict of Interest Statement: None declared. (...truncated)


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Ranjit Kumar Thirumaran, Justo Lorenzo Bermejo, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Walter Goessler, Marie Vahter, Giovanni S. Leonardi, Felicity Clemens, Tony Fletcher, Kari Hemminki, Rajiv Kumar. Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin, Carcinogenesis, 2006, pp. 1676-1681, 27/8, DOI: 10.1093/carcin/bgi381