Abstract
BackgroundThe 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).MethodsIn this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and alcohol consumption. Univariate and multivariate logistic regression analyses were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI).ResultsWe found that individuals with CHRNA5 rs3841324 combined variant genotypes (ins/del+del/del) had a >1.5-fold elevated risk for NPC than those with the ins/ins genotype (adjusted OR = 1.52; 95% CI, 1.16–2.00), especially among ever smokers (adjusted OR = 2.07; 95% CI, 1.23–3.48). The combined variant genotypes acted jointly with cigarette smoking to contribute to a 4.35-fold increased NPC risk (adjusted OR = 4.35; 95% CI, 2.57–7.38). There was a dose-response relationship between deletion alleles and NPC susceptibility (trend test, P = 0.011).ConclusionsOur results suggest that genetic variants on the 15q25.1 lung cancer susceptibility locus may influence susceptibility to NPC, particularly for smoking-associated NPC. Such work may be helpful to facilitate an understanding of the etiology of smoking-associated cancers and improve prevention efforts.
Highlights
Cigarette smoking is a major public health problem, accounting for 5 million deaths annually worldwide [1], and contributing to 31% and 6% of all cancer deaths in men and women worldwide for people between 30 and 69 years of age, respectively [2]
A component of cigarettes, can promote cancer cell proliferation, survival, migration, invasion, etiology, and development [3], Nicotine has been shown to be involved with the pathogenesis of many cancers, including nasopharyngeal carcinoma (NPC) [4]; there is no evidence that the carcinogenic mechanisms associated with nicotine and genetic variants influence susceptibility to NPC
To determine whether or not genetic variations in the 15q25.1 lung cancer susceptibility locus are implicated in the carcinogenesis of cigarette smoking-mediated cancer risk other than lung cancer, we evaluated the association between the CHRNA5 rs3841324 polymorphism and NPC risk in general and in subgroups of subjects stratified by age, gender, cigarette smoking, alcohol consumption, and pathology, and explored the joint effect between CHRNA5 rs3841324 and cigarette smoke exposure on NPC risk with 400 patients newly diagnosed with NPC and 491 cancer-free healthy controls
Summary
Cigarette smoking is a major public health problem, accounting for 5 million deaths annually worldwide [1], and contributing to 31% and 6% of all cancer deaths in men and women worldwide for people between 30 and 69 years of age, respectively [2]. Genome-wide association studies (GWAS) have identified that chromosome 15q25.1, composed of nicotinic acetylcholine receptor genes, including CHRNA5 and CHRNA3, are lung cancer susceptibility regions [5,6] and play a potential role in multiple smoking-related phenotypes and nicotine dependence [7]. There is only one study that has examined the association between genetic variants at the 15q25.1 lung cancer susceptibility locus (rs8034191 and rs1051730) and the risk of another smoking-associated cancer other than lung cancer (pancreatic cancer) and found no significant association [14] It is unclear whether or not the 15q25.1 lung cancer susceptibility locus is confined to the lung or influences cancer susceptibility related to carcinogenic compound exposure in cigarette smoking. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC)
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