机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Department of Epidemiology, China Medical University School of Public Health, Shenyang, China[4]Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA[5]Clinical Research Promotion and Development Center, Shanghai Hospital Development Center, Shanghai, China
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(2)B(7,) 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.
基金：
This work was supported by grant from
the National Natural Science Foundation
of China (Grant No. 81573231).
第一作者机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China[5]Clinical Research Promotion and Development Center, Shanghai Hospital Development Center, Shanghai, China[*1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, No. 227 South Chongqing Road, Shanghai 200025, China.
推荐引用方式(GB/T 7714)：
Qian Ying,Xie Li,Li Lei,et al.Association between sex hormones regulation-related SNP rs12233719 and lung cancer risk among never-smoking Chinese women[J].CANCER MEDICINE.2021,10(5):1880-1888.doi:10.1002/cam4.3772.
APA：
Qian, Ying,Xie, Li,Li, Lei,Feng, Tienan,Zhu, Tengteng...&Qian, Biyun.(2021).Association between sex hormones regulation-related SNP rs12233719 and lung cancer risk among never-smoking Chinese women.CANCER MEDICINE,10,(5)
MLA：
Qian, Ying,et al."Association between sex hormones regulation-related SNP rs12233719 and lung cancer risk among never-smoking Chinese women".CANCER MEDICINE 10..5(2021):1880-1888
