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

Abstract

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 UGT2 B7, 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.

• Authors: Ying Qian, Li Xie, Lei Li, Tienan Feng, Tengteng Zhu, Ruoyang Wang, Yuqing Yang, Baosen Zhou, Herbert Yu, Biyun Qian
• Journal: Cancer medicine (Cancer Med) Vol. 10 Issue 5 Pg. 1880-1888 (03 2021) ISSN: 2045-7634 [Electronic] United States
• PMID: 33595913 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• RNA, Messenger
• SHBG protein, human
• Sex Hormone-Binding Globulin
• UGT2B7 protein, human
• Glucuronosyltransferase

Topics

• Adult
• Alleles
• Carcinoma, Non-Small-Cell Lung (blood, genetics, metabolism)
• Case-Control Studies
• Chi-Square Distribution
• China
• Female
• Gene Expression Profiling
• Gene Frequency
• Genome-Wide Association Study
• Glucuronosyltransferase (genetics, metabolism)
• Humans
• Logistic Models
• Lung Neoplasms (blood, genetics, metabolism)
• Mutation, Missense
• Non-Smokers
• Odds Ratio
• Polymorphism, Single Nucleotide
• RNA, Messenger (metabolism)
• Sex Hormone-Binding Globulin (analysis, genetics)
• Up-Regulation