Single-Nucleotide Polymorphisms in Nucleotide Excision Repair Genes, Cigarette Smoking, and the Risk of Head and Neck Cancer

Abstract

Background Cigarette smoking is associated with increased head and neck cancer (HNC) risk. Tobacco-related carcinogens are known to cause bulky DNA adducts. Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC. Methods Using population-based case-control data from the Carolina Head and Neck Cancer Epidemiology Study (1,227 cases, 1,325 controls), race-stratified (white, African American) conventional and hierarchical logistic regression models were utilized to estimate odds ratios (OR) with 95% intervals (I) for the independent and joint effects of cigarette smoking and 84 single nucleotide polymorphisms (SNPs) from 15 NER genes on HNC risk. Results The odds of HNC were elevated among ever cigarette smokers, and increased with smoking duration and frequency. Among whites, rs4150403 on ERCC3 was associated with increased HNC odds (AA+AG vs. GG, OR=1.28, 95% I=1.01,1.61). Among African Americans, rs4253132 on ERCC6 was associated with decreased HNC odds (CC+CT vs. TT, OR=0.62, 95% I=0.45,0.86). Interactions between ever cigarette smoking and three SNPs (rs4253132 on ERCC6, rs2291120 on DDB2, and rs744154 on ERCC4) suggested possible departures from additivity among whites. Conclusions We did not find associations between some previously studied NER variants and HNC. We did identify new associations between two SNPs and HNC and three suggestive cigarette-SNP interactions to consider in future studies. Impact We conducted one of the most comprehensive evaluations of NER variants, identifying a few SNPs from biologically plausible candidate genes associated with HNC and possibly interacting with cigarette smoking.

Single nucleotide polymorphisms in nucleotide excision repair genes, cancer treatment, and head and neck cancer survival

“…The Carolina Head and Neck Cancer Epidemiology (CHANCE) Study is a population-based case–control study of 1,389 cases and 1,396 controls from North Carolina (NC) [18–22]. For the present analysis, we compared survival among cases by treatment and genotype.…”

“…For the present analysis, we compared survival among cases by treatment and genotype. All cases were 20–80 years of age and were identified from the NC Central Cancer Registry between 1 January 2002 and 28 February 2006 using rapid case ascertainment [18–22]. Cases with tumors in the oral cavity, oropharynx, hypo-pharynx, larynx, and HNC not otherwise specified (NOS) were included, while tumors of the salivary glands, naso-pharynx, nasal cavity, and nasal sinuses were excluded [18–22].…”

“…All cases were 20–80 years of age and were identified from the NC Central Cancer Registry between 1 January 2002 and 28 February 2006 using rapid case ascertainment [18–22]. Cases with tumors in the oral cavity, oropharynx, hypo-pharynx, larynx, and HNC not otherwise specified (NOS) were included, while tumors of the salivary glands, naso-pharynx, nasal cavity, and nasal sinuses were excluded [18–22]. Self-reported demographic and behavioral information and biologic samples (~90 % blood, ~10 % buccal cells) were collected during a nurse-administered interview [18–22].…”

Associations of ERCC4 rs1800067 Polymorphism with Cancer Risk: an Updated Meta-analysis

“…Four publications were excluded because of meta-analysis, control group had cancer patients or not published in English. Finally, 26 full-text articles with eligibility were included in this meta-analysis (Smith et al, 2003;Huang et al, 2006;Mechanic et al, 2006;Moreno et al, 2006;Crew et al, 2007;Jorgensen et al, 2007;Chang et al, 2008;Hung et al, 2008;McWilliams et al, 2008;Rajaraman et al, 2008;Abbasi et al, 2009;Han et al, 2009;Joshi et al, 2009;Agalliu et al, 2010;Rajaraman et al, 2010;Doherty et al, 2011;Krupa et al, 2011;Smith et al, 2011;Gil et al, 2012;Yu et al, 2012;Cheng et al, 2013;Santos et al, 2013;Wang et al, 2013;Wyss et al, 2013;Kohlhase et al, 2014;Steck et al, 2014). The flow chart which reflected the details of article selection was presented in Figure 1.…”

“…Recently, several studies continued to explore the association of ERCC4 rs1800067 polymorphism with risk of cancer but the results were controversial (Cheng et al, 2013;Santos et al, 2013;Wang et al, 2013;Wyss et al, 2013;Kohlhase et al, 2014;Steck et al, 2014). Aiming at elucidating the exact relation between ERCC4 rs1800067 A/G polymorphism with risk of cancer, we perform the current meta-analysis by collecting the data from published case-control studies concerning the role of rs1800067 polymorphism in carcinogenesis.…”