title: CHRNA9 polymorphisms and smoking exposure synergize to increase the risk of breast cancer in Taiwan.
abstract: Previous studies indicated that smoking exposure is associated with an increased risk of breast cancer, and α9-nicotine acetylcholine receptors (α9-nAChRs) are involved in breast tumorigenesis. However, no studies have explored the joint effect of α9-nAChRs (CHRNA9) genes and cigarette smoking exposure on breast cancer risk. A case-control study was conducted on 737 breast cancer patients and 719 age-matched healthy controls. Three single-nucleotide polymorphisms (SNPs) of CHRNA9 located in the promoter region were genotyped and compared between cases and controls to identify those SNPs associated with breast cancer susceptibility. A dual-luciferase reporter assay was used to analyze the promoter activities of these SNPs of the CHRNA9 gene. After a Bonferroni correction, the G allele of the CHRNA9 rs7329797 SNP was significantly associated with an increased risk of developing breast cancer compared with A/A genotype carriers (odds ratio, 1.8; 95% confidence interval, 1.2-2.6). A multiplicative interaction between passive smoking exposure and the CHRNA9 rs73229797 SNP on the risk of breast malignancy was observed. A functional assay further showed that rs73229797 was associated with increased promoter activity of the CHRNA9 gene. Our findings support a significant interaction effect existing between the CHRNA9 gene and smoking exposure on the risk of breast cancer development.
authors.affiliation: PhD Program for Neural Regenerative Medicine and Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei 23561, Taiwan, Department of Surgery, Taipei Medical University Hospital, Taipei 11031, Taiwan, Department of Surgery, Taipei Medical University-Wan Fang Hospital, Taipei 11696, Taiwan and School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing St., Taipei 11031, Taiwan.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Chia-Hwa
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Tu
authors.affiliation: Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei 23561, Taiwan.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Surgery, Taipei Medical University Hospital, Taipei 11031, Taiwan.
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Hung
authors.affiliation: Department of Surgery, Taipei Medical University-Wan Fang Hospital, Taipei 11696, Taiwan and.
authors.forename: Mao-Chih
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing St., Taipei 11031, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Chuang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing St., Taipei 11031, Taiwan hychiou@tmu.edu.tw.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D013624:Taiwan
chemical_list: C498540:CHRNA9 protein, human; D011978:Receptors, Nicotinic