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Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.

ABSTRACT: Importance:Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood. Objective:To assess the association between metabolomics and lung cancer risk among never-smoking women. Design, Setting, and Participants:This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018. Exposures:Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39?416 metabolites were measured. Main Outcomes and Measures:Incident lung cancer. Results:Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P?

SUBMITTER: Seow WJ

PROVIDER: S-EPMC6755532 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.

Seow Wei Jie WJ Shu Xiao-Ou XO Nicholson Jeremy K JK Holmes Elaine E Walker Douglas I DI Hu Wei W Cai Qiuyin Q Gao Yu-Tang YT Xiang Yong-Bing YB Moore Steven C SC Bassig Bryan A BA Wong Jason Y Y JYY Zhang Jinming J Ji Bu-Tian BT Boulangé Claire L CL Kaluarachchi Manuja M Wijeyesekera Anisha A Zheng Wei W Elliott Paul P Rothman Nathaniel N Lan Qing Q

JAMA network open 20190904 9

<h4>Importance</h4>Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood.<h4>Objective</h4>To assess the association between metabolomics and lung cancer risk among never-smoking women.<h4>Design, setting, and participants</h4>This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study ...[more]

PMID: 31539079

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Project description:BackgroundThe 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.MethodsCandidate 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.ResultsBeginning 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.ConclusionOur 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.

Project description:BackgroundLung cancer rates among never-smoking women in Xuanwei and Fuyuan in China are among the highest in the world and have been attributed to the domestic use of smoky (bituminous) coal for heating and cooking. However, the key components of coal that drive lung cancer risk have not been identified.ObjectivesWe aimed to investigate the relationship between lifelong exposure to the constituents of smoky coal (and other fuel types) and lung cancer.MethodsUsing a population-based case-control study of lung cancer among 1,015 never-smoking female cases and 485 controls, we examined the association between exposure to 43 household air pollutants and lung cancer. Pollutant predictions were derived from a comprehensive exposure assessment study, which included methylated polycyclic aromatic hydrocarbons (PAHs), which have never been directly evaluated in an epidemiological study of any cancer. Hierarchical clustering and penalized regression were applied in order to address high colinearity in exposure variables.ResultsThe strongest association with lung cancer was for a cluster of 25 PAHs [odds ratio (OR): 2.21; 95% confidence interval (CI): 1.67, 2.87 per 1 standard deviation (SD) change], within which 5-methylchrysene (5-MC), a mutagenic and carcinogenic PAH, had the highest individual observed OR (5.42; 95% CI: 0.94, 27.5). A positive association with nitrogen dioxide ([Formula: see text]) was also observed (OR: 2.06; 95% CI: 1.19, 3.49). By contrast, neither benzo(a)pyrene (BaP) nor fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]) were associated with lung cancer in the multipollutant models.ConclusionsTo our knowledge, this is the first study to comprehensively evaluate the association between lung cancer and household air pollution (HAP) constituents estimated over the entire life course. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products, including methylated PAHs, may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. https://doi.org/10.1289/EHP4913.

Project description:ImportanceEstimating absolute risk of lung cancer for never-smoking individuals is important to inform lung cancer screening programs.ObjectivesTo integrate data on environmental tobacco smoke (ETS), a known lung cancer risk factor, with a polygenic risk score (PRS) that captures overall genetic susceptibility, to estimate the absolute risk of lung adenocarcinoma (LUAD) among never-smokers in Taiwan.Design, setting, and participantsThe analyses were conducted in never-smoking women in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma, a case-control study. Participants were recruited between September 17, 2002, and March 30, 2011. Data analysis was performed from January 17 to July 15, 2022.ExposuresA PRS was derived using 25 genetic variants that achieved genome-wide significance (P < 5 × 10-8) in a recent genome-wide association study, and ETS was defined as never exposed, exposed at home or at work, and exposed at home and at work.Main outcomes and measuresThe Individualized Coherent Absolute Risk Estimator software was used to estimate the lifetime absolute risk of LUAD in never-smoking women aged 40 years over a projected 40-year span among the controls by using the relative risk estimates for the PRS and ETS exposures, as well as age-specific lung cancer incidence rates for never-smokers in Taiwan. Likelihood ratio tests were conducted to assess an additive interaction between the PRS and ETS exposure.ResultsData were obtained on 1024 women with LUAD (mean [SD] age, 59.6 [11.4] years, 47.9% ever exposed to ETS at home, and 19.5% ever exposed to ETS at work) and 1024 controls (mean [SD] age, 58.9 [11.0] years, 37.0% ever exposed to ETS at home, and 14.3% ever exposed to ETS at work). The overall average lifetime 40-year absolute risk of LUAD estimated using PRS alone was 2.5% (range, 0.6%-10.3%) among women never exposed to ETS. When integrating both ETS and PRS data, the estimated absolute risk was 3.7% (range, 0.6%-14.5%) for women exposed to ETS at home or work and 5.3% (range, 1.2%-12.1%) for women exposed to ETS at home and work. A super-additive interaction between ETS and the PRS (P = 6.5 × 10-4 for interaction) was identified.Conclusions and relevanceThis study found differences in absolute risk of LUAD attributed to genetic susceptibility according to levels of ETS exposure in never-smoking women. Future studies are warranted to integrate these findings in expanded risk models for LUAD.

Project description:ObjectivesOccupational lung carcinogens have been primarily studied in men. The aim of this study was to investigate occupational lung cancer risk in a cohort of Chinese non-smoking women.MethodsIn 1996-2000, 71 067 non-smoking women who had held a job outside the home were interviewed for the prospective Shanghai Women's Health Study in China. Exposure to lung carcinogens was assessed by matching occupation and industry titles from lifetime occupational histories with lists of jobs identified by the International Agency for Research on Cancer to have potential exposure to: (1) known (A-list); or (2) suspected (B-list) carcinogens. In addition, similar occupational titles were grouped independent of the a priori defined lists. Relative risks (RRs) were calculated using Cox proportional hazards regression.ResultsDuring follow-up through 2005, 219 incident lung cancer cases were diagnosed. Jobs on the A-list and B-list were held by 0.8-6.7% and 2.7-9.4% of the cohort, respectively. Overall, ever holding any job on the A-list or B-list was not associated with lung cancer incidence. Indications of excess risk were found for two subgroups: painters (A-list) and rubber workers (B-list) (RR = 2.0 and 1.7, respectively, p<or=0.1). An exploratory analysis of 35 occupational categories independent of the lists showed significantly increased risks for leather products/shoes, wood/paper products and miscellaneous production/transportation. The former two of these categories were similar to subgroups of the B-list, but broader than the specific a priori defined jobs.ConclusionsSignificantly elevated lung cancer risk was associated with employment in some broad occupational categories that also included jobs with potential exposure to suspected carcinogens (B-list). The results suggest that although similar exposures to those described on the B-list may play a role in this cohort of Chinese women, carcinogenic exposure may not be restricted only to the jobs on the B-list.

Dataset Information

Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.

Publications

Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.

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