Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study

Abstract Background Areca nut (AN) was classified as a carcinogen by the International Agency for Research on Cancer (IARC) of the WHO in 2003. AN has the same carcinogenic components as cigarettes, such as benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), but its effe...

Full description

Saved in:
Bibliographic Details
Main Authors: Yixuan Li, Jing Zhou, Lirong Liu, Chaoyong Zhu, Ziyue Luo, Na Li, Pengfei Lyu, Jing Zhang, Tian Xie, Yipeng Ding, Sha Xiao
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-025-14020-3
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849737675359125504
author Yixuan Li
Jing Zhou
Lirong Liu
Chaoyong Zhu
Ziyue Luo
Na Li
Pengfei Lyu
Jing Zhang
Tian Xie
Yipeng Ding
Sha Xiao
author_facet Yixuan Li
Jing Zhou
Lirong Liu
Chaoyong Zhu
Ziyue Luo
Na Li
Pengfei Lyu
Jing Zhang
Tian Xie
Yipeng Ding
Sha Xiao
author_sort Yixuan Li
collection DOAJ
description Abstract Background Areca nut (AN) was classified as a carcinogen by the International Agency for Research on Cancer (IARC) of the WHO in 2003. AN has the same carcinogenic components as cigarettes, such as benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), but its effects on interactions with genetic factors related to lung cancer have rarely been investigated.  Methods Here, a propensity score-matched case‒control study was conducted in Hainan, which included 445 patients with lung cancer and 445 cancer-free controls. Then, the associations between single-nucleotide polymorphisms (SNPs) in the CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction effects with AN chewing and smoking on lung cancer were analyzed. In addition, we explored the associations among AN, cigarettes, and genes related to lung cancer using the Comparative Toxicogenomics Database (CTD). Results The results indicate that the CHRNA3 rs938682 (A > G) GG genotype (OR = 0.669, 95% CI = 0.454 ~ 0.984, P = 0.042) can decrease the risk of lung cancer. The CHRNB4 rs7178270 (C > G) GG genotype (OR = 1.729, 95% CI = 1.168 ~ 2.571, P = 0.006) can increase the risk of lung cancer. The CHRNA5 rs17486278 CC genotype was associated with a high risk in males, smokers, and drinkers. The CHRNA3 rs938682 GG genotype was associated with a low risk in AN chewers. The CHRNB4 rs7178270 GG genotype was associated with high risk in drinkers and AN chewers. CHRNB4 rs7178270 and AN chewing have an interaction effect on lung cancer in Hainan. Conclusions This study is the first to elucidate the hidden impacts of AN on lung cancer and provides a key evidence regarding the interactive effects of AN and cigarettes with SNPs in nAChRs genes on lung cancer. Graphical Abstract
format Article
id doaj-art-dd0c258ef18841b99677b66e81270e55
institution DOAJ
issn 1471-2407
language English
publishDate 2025-04-01
publisher BMC
record_format Article
series BMC Cancer
spelling doaj-art-dd0c258ef18841b99677b66e81270e552025-08-20T03:06:51ZengBMCBMC Cancer1471-24072025-04-0125111710.1186/s12885-025-14020-3Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control studyYixuan Li0Jing Zhou1Lirong Liu2Chaoyong Zhu3Ziyue Luo4Na Li5Pengfei Lyu6Jing Zhang7Tian Xie8Yipeng Ding9Sha Xiao10School of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Heinz Mehlhorn Academician Workstation, Hainan Medical UniversitySchool of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Heinz Mehlhorn Academician Workstation, Hainan Medical UniversityDepartment of Respiratory and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversityMedical Examination Center of Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversitySchool of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Heinz Mehlhorn Academician Workstation, Hainan Medical UniversitySchool of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Heinz Mehlhorn Academician Workstation, Hainan Medical UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Hainan Medical UniversitySchool of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Heinz Mehlhorn Academician Workstation, Hainan Medical UniversityDepartment of Respiratory and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversityDepartment of Respiratory and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversitySchool of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Heinz Mehlhorn Academician Workstation, Hainan Medical UniversityAbstract Background Areca nut (AN) was classified as a carcinogen by the International Agency for Research on Cancer (IARC) of the WHO in 2003. AN has the same carcinogenic components as cigarettes, such as benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), but its effects on interactions with genetic factors related to lung cancer have rarely been investigated.  Methods Here, a propensity score-matched case‒control study was conducted in Hainan, which included 445 patients with lung cancer and 445 cancer-free controls. Then, the associations between single-nucleotide polymorphisms (SNPs) in the CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction effects with AN chewing and smoking on lung cancer were analyzed. In addition, we explored the associations among AN, cigarettes, and genes related to lung cancer using the Comparative Toxicogenomics Database (CTD). Results The results indicate that the CHRNA3 rs938682 (A > G) GG genotype (OR = 0.669, 95% CI = 0.454 ~ 0.984, P = 0.042) can decrease the risk of lung cancer. The CHRNB4 rs7178270 (C > G) GG genotype (OR = 1.729, 95% CI = 1.168 ~ 2.571, P = 0.006) can increase the risk of lung cancer. The CHRNA5 rs17486278 CC genotype was associated with a high risk in males, smokers, and drinkers. The CHRNA3 rs938682 GG genotype was associated with a low risk in AN chewers. The CHRNB4 rs7178270 GG genotype was associated with high risk in drinkers and AN chewers. CHRNB4 rs7178270 and AN chewing have an interaction effect on lung cancer in Hainan. Conclusions This study is the first to elucidate the hidden impacts of AN on lung cancer and provides a key evidence regarding the interactive effects of AN and cigarettes with SNPs in nAChRs genes on lung cancer. Graphical Abstracthttps://doi.org/10.1186/s12885-025-14020-3Areca nutCigarettenAChRsSNPLung cancer
spellingShingle Yixuan Li
Jing Zhou
Lirong Liu
Chaoyong Zhu
Ziyue Luo
Na Li
Pengfei Lyu
Jing Zhang
Tian Xie
Yipeng Ding
Sha Xiao
Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study
BMC Cancer
Areca nut
Cigarette
nAChRs
SNP
Lung cancer
title Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study
title_full Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study
title_fullStr Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study
title_full_unstemmed Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study
title_short Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study
title_sort association of snps in nachrs genes areca nut chewing and smoking and their interaction with lung cancer in hainan china a case control study
topic Areca nut
Cigarette
nAChRs
SNP
Lung cancer
url https://doi.org/10.1186/s12885-025-14020-3
work_keys_str_mv AT yixuanli associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT jingzhou associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT lirongliu associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT chaoyongzhu associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT ziyueluo associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT nali associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT pengfeilyu associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT jingzhang associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT tianxie associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT yipengding associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy
AT shaxiao associationofsnpsinnachrsgenesarecanutchewingandsmokingandtheirinteractionwithlungcancerinhainanchinaacasecontrolstudy