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      Association between air pollution and primary liver cancer in European and east Asian populations: a Mendelian randomization study

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          Abstract

          Purpose

          The incidence of primary liver cancer is increasing year by year, with environmental factors playing a non-negligible role. At present, many studies are still disputing whether air pollution is associated with primary liver cancer incidence, and it is difficult to draw causal inferences. Therefore, in this study, we used two-sample Mendelian randomization (MR) to assess the causal relationship between air pollution (including PM2.5, PM2.5–10, PM10, nitrogen dioxide and nitrogen oxides) and primary liver cancer risk and its related biomarkers (Alpha-fetoprotein, Osteopontin, Glypican-3 and Arginase-1).

          Patients and methods

          We used large-scale publicly available genome-wide association studies (GWAS) summary data to conduct MR analyses of European and East Asian populations. Inverse variance weighted (IVW) method was used as the main analysis method, and weighted median model, MR-Egger, simple model and weighted model methods were selected for quality control. Heterogeneity was checked by the Cochran’s Q test. The MR-Egger regression and the MR-PRESSO global test detect pleiotropy. The sensitivity analysis was performed using the leave-one-out method.

          Results

          Between air pollution and primary liver cancer in either European (PM2.5: p = 0.993; PM2.5–10: p = 0.833; PM10: p = 0.257; nitrogen dioxide: p = 0.215; nitrogen oxides: p = 0.614) or East Asian (PM2.5: p = 0.718; PM2.5–10: p = 0.362; PM10: p = 0.720; nitrogen dioxide: p = 0.101; nitrogen oxides: p = 0.760) populations were found no statistical association. Notably, there was a causal relationship between nitrogen oxides and Arginase-1, a biomarker associated with hepatocellular differentiation, statistically significant associations remained after deletion for single nucleotide polymorphisms (SNPs) associated with alcohol intake frequency, Body mass index (BMI) and cancers (Beta: 4.46; 95%CI: 0.83–8.08; p = 0.015). There was no heterogeneity or pleiotropy in the results.

          Conclusion

          This MR study found no evidence to support a causality between air pollution and primary liver cancer in European and East Asian populations, but nitrogen oxides may affect hepatocellular differentiation.

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          Most cited references56

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

            Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
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              The UK Biobank resource with deep phenotyping and genomic data

              The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
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                Author and article information

                Contributors
                Journal
                Front Public Health
                Front Public Health
                Front. Public Health
                Frontiers in Public Health
                Frontiers Media S.A.
                2296-2565
                27 July 2023
                2023
                : 11
                : 1212301
                Affiliations
                [1] 1Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University , Changsha, China
                [2] 2Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University , Changsha, Hunan, China
                [3] 3National Health Committee (NHC) Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital , Changsha, Hunan, China
                [4] 4Hunan Provincial Key Laboratory of Clinical Epidemiology , Changsha, Hunan, China
                Author notes

                Edited by: Ghulam Mujtaba Kayani, Hubei University of Economics, China

                Reviewed by: Ying Wu, Southern Medical University, China; Marija Jevtic, University of Novi Sad, Serbia

                *Correspondence: Jiabi Qin, qinjiabi123@ 123456163.com
                Article
                10.3389/fpubh.2023.1212301
                10415013
                37575092
                9ff3cdf4-d63e-46cd-af8a-b581dad4b19b
                Copyright © 2023 Sun, Gao, Luo, Wang, Zhong and Qin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 April 2023
                : 12 July 2023
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 56, Pages: 12, Words: 7953
                Funding
                Funded by: National Natural Science Foundation Program of China
                Award ID: 82073653
                Award ID: 81803313
                Funded by: Hunan Outstanding Youth Fund Project
                Award ID: 2022JJ10087
                Funded by: National Key Research and Development Project
                Award ID: 2018YFE0114500
                Funded by: China Postdoctoral Science Foundation, doi 10.13039/501100002858;
                Award ID: 2020M682644
                Funded by: Hunan Provincial Key Research and Development Program
                Award ID: 2018SK2063
                Funded by: Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention
                Award ID: KF2020006
                Funded by: Natural Science Foundation of Hunan Province, doi 10.13039/501100004735;
                Award ID: 2018JJ2551
                Funded by: Natural Science Foundation of Hunan Province of China
                Award ID: 2022JJ40207
                Funded by: Changsha Municipal Natural Science Foundation
                Award ID: kq2202470
                Funded by: Hunan Provincial Science and Technology Talent Support Project
                Categories
                Public Health
                Original Research
                Custom metadata
                Environmental health and Exposome

                air pollution,primary liver cancer,particulate matter,nitrogen oxides,biomarkers

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