Laryngeal cancer risk associated with smoking and alcohol consumption is modified by genetic polymorphisms in ERCC5, ERCC6 and RAD23B but not by polymorphisms in five other nucleotide excision repair genes
Rashda Abbasi
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorHeribert Ramroth
Department of Tropical Hygiene and Public Health, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorHeiko Becher
Department of Tropical Hygiene and Public Health, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorAndreas Dietz
Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany
Search for more papers by this authorPeter Schmezer
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Odilia Popanda
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany
Fax: +49-622-142-3359.
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, GermanySearch for more papers by this authorRashda Abbasi
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorHeribert Ramroth
Department of Tropical Hygiene and Public Health, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorHeiko Becher
Department of Tropical Hygiene and Public Health, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorAndreas Dietz
Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany
Search for more papers by this authorPeter Schmezer
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Odilia Popanda
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany
Fax: +49-622-142-3359.
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, GermanySearch for more papers by this authorAbstract
Laryngeal cancer is known to be associated with smoking and high alcohol consumption. Nucleotide excision repair (NER) plays a key role in repairing DNA damage induced by these exposures and might affect laryngeal cancer susceptibility. In a population-based case-control study including 248 cases and 647 controls, the association of laryngeal cancer with 14 single nucleotide polymorphisms (SNPs) in 8 NER genes (XPC, XPA, ERCC1, ERCC2, ERCC4, ERCC5, ERCC6 and RAD23B) was analyzed with respect to smoking and alcohol exposure. For genotyping, sequence specific hybridization probes were used. Data were evaluated by conditional logistic regression analysis, stratified for age and gender, and adjusted for smoking, alcohol consumption and education. Pro-carriers of ERCC6 Arg1230Pro showed a decreased risk for laryngeal cancer (OR = 0.53, 95% CI 0.34–0.85), strongest in heavy smokers and high alcohol consumers. ERCC5 Asp1104His was associated with risk in heavy smokers (OR = 1.70, 95% CI 1.1–2.5). Val-carriers of RAD23B Ala249Val had an increased cancer risk in heavy smokers (OR = 1.6, 95% CI 1.1–2.5) and high alcohol consumers (OR = 2.0, 95% CI 1.1–3.4). The combined effect of smoking and alcohol intake affected risk, at high exposure level, for ERCC6 1230Pro carriers (OR = 0.47, 95% CI 0.22–0.98) and RAD23B 249Val carriers (OR = 2.6, 95% CI 1.3–4.9). When tested for gene–gene interaction, presence of 3 risk alleles in the XPC-RAD23B complex increased the risk 2.1-fold. SNPs in the other genes did not show a significant association with laryngeal cancer risk. We conclude that common genetic variations in NER genes can significantly modify laryngeal cancer risk. © 2009 UICC
Supporting Information
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IJC_24442_sm_SuppTable1.doc244 KB | Supporting Information Table 1. PRIMERS, HYBRIDIZATION PROBES AND RESTRICTION ENZYMES FOR GENOTYPE ANALYSIS |
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