Volume 125, Issue 6 pp. 1431-1439
Epidemiology

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

Rashda Abbasi

Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany

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Heribert Ramroth

Heribert Ramroth

Department of Tropical Hygiene and Public Health, University of Heidelberg, Heidelberg, Germany

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Heiko Becher

Heiko Becher

Department of Tropical Hygiene and Public Health, University of Heidelberg, Heidelberg, Germany

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Andreas Dietz

Andreas Dietz

Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany

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Peter Schmezer

Peter Schmezer

Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany

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Odilia Popanda

Corresponding 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 author
First published: 14 July 2009
Citations: 79

Abstract

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

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