Association between sex hormones regulation-related SNP rs12233719 and lung cancer risk among never-smoking Chinese women.

Background: The mechanism of rapidly increased non-small cell lung cancer (NSCLC) among never-smoking Chinese women has not been elucidated. Ovarian sex steroid hormones have been suggested to counteract lung cancer development, and sex hormone-binding globulin (SHBG) is essential in sex hormones regulation. This study aims to exploring single nucleotide polymorphisms (SNPs) in genomic regions associated with SHBG concentrations that contributed to never-smoking female NSCLC.

Methods: Candidate genes were selected by a genome-wide association (GWAS) meta-analysis and gene expression profiles of never-smoking NSCLC of Chinese women. The candidate SNPs limited to common minor allele frequency (MAF), missense variant, ethnic heterogeneous distribution, and SNPs were genotyped using the TaqMan method. A two-stage case-control design was adopted for exploration and validation of associations between candidate SNPs and risk of NSCLC. All participants were never-smoking Chinese women. Chi-square test and multivariate logistic regression were applied.

Results: Beginning with 12 genomic regions associated with circulating SHBG concentrations and gene expression profiles from never-smoking NSCLC in Chinese women, candidate SNP rs12233719 and rs7439366 both located in candidate gene UGT B which may be related to circulating SHBG concentrations and cancer risk, were identified. A two-stage case-control study was conducted in Shenyang and Tianjin represented as the training stage and validation stage, respectively. Under the dominant model, compared to individuals with the wild G/G genotype, the adjusted OR of those with the T allele was 1.58 (95% CI: 1.15-2.16) in Chinese Shenyang training set, and was 1.49 (95% CI: 1.02-2.18) in Chinese Tianjin validation set, both accompanied with a significant trend relationship consistently. UGT2B7 was upregulated in female NSCLC patients' tumor tissues and was associated with a poor prognosis in NSCLC.

Conclusion: Our findings indicated that a sex hormones regulation-related SNP rs12233719 was associated with never-smoking female lung cancer risk, which might partially explain NSCLC-susceptibility in Chinese women.