Polymorphisms of CHRNA3 and CHRNA5: Head and neck cancer and cigarette consumption intensity in a Brazilian population

Abstract

BackgroundCigarette consumption has been identified as the main non‐etiological factor in head and neck cancer (HNC) development. One of the main compounds in cigarettes is nicotine, which binds directly to nicotine acetylcholine receptors (nAchRs) in the body, which are encoded by different genes of the CHRNA family. Polymorphisms in some of these genes have been studied in relation to the risk of HNC and cigarette consumption intensity. The aim of this study was to evaluate whether there were associations between the CHRNA3 (rs578776) and CHRNA5 (rs16969968) polymorphisms and HNC risk and between the polymorphisms and the intensity of cigarette consumption.MethodsA total of 1,067 individuals from Heliopolis Hospital in São Paulo were investigated, including 619 patients with HNC and 448 patients without diagnosed tumors. All participants answered a questionnaire about sociodemographic information and cigarette consumption data. The polymorphisms were determined by TaqMan genotyping by real‐time PCR.ResultsThe polymorphisms studied, rs578776 (CHRNA3) and rs16969968 (CHRNA5), did not have an association with HNC risk, but the rs16969968 homozygous genotype was associated with increased cigarette consumption intensity (OR 1.93, 95% CI 1.05–3.58).ConclusionThe polymorphism CHRNA5 can be considered an indirect risk factor for neoplasms in these Brazilian samples when cigarette consumption increased.

CHRNA5/CHRNA3 polymorphisms and tobacco smoking risk in a Brazilian population sample

“…Herein, variant allele frequencies were 24% and 45% for CHRNA5 rs16969968 and CHRNA3 rs578776, respectively. This distribution appears to be intermediary compared to other populations, and similar to previous studies performed on Brazilian populations [22,23].…”

“…Apparently, this is the case of Brazil, a country characterized by having a mixed population. However, very few studies have been carried out in the Brazilian population [22,23].…”

The CHRNA5 polymorphism (rs16969968) and its association with waterpipe smoking addiction among Jordanians

“…Similar distribution of rs16969968 alleles in the Palestinian and Algerian Arab populations was reported (Ayesh, Al-Masri, & Abed, 2018;Mimouni et al, 2020). The observed trend in the distribution of rs16969968 alleles is similar to that reported in other world populations (Aroche et al, 2020;Hubacek et al, 2019;Silva et al, 2019).…”

“…One single nucleotide polymorphisms (SNP) that showed strong relation to tobacco smoking behavior/dependence? is the rs16969968 SNP in exon 5 of CHRNA5 (Hubacek et al, 2019;Silva et al, 2019). This SNP replaces an aspartate into asparagine at nucleotide 398 of the a5 subunit.…”

Genetic susceptibility to nicotine addiction: Advances and shortcomings in our understanding of the CHRNA5/A3/B4 gene cluster contribution

“…The gene has a pLI score of 0.01 (higher scores indicate poorer tolerance to mutations) with 33% haploinsufficiency, indicating an overall high tolerance to mutation. In one recent study, the authors have evaluated the association between a CHRNA3 (rs578776-NG_016143.1) polymorphism with head and neck cancer (HCN) development and the intensity of cigarette smoking by using a TaqMan genotyping method by real-time PCR, in a cohort of 1,067 patients from Sao Paulo Hospital (Silva et al, 2019). Results from this study did not reveal any statistically significant association between the identified SNP with both HCN and smoking risk as compared to control groups (Silva et al, 2019).…”