中国10个地区成年男性Y染色体嵌合缺失流行病学分布及其与肺癌的前瞻性关联研究

赵禹碹; 宋明钰; 吕筠; 余灿清; 裴培; 杜怀东; 陈君石; 陈铮鸣; 李立明; 孙点剑一; 代表中国慢性病前瞻性研究项目协作组

Abstract

赵禹碹,宋明钰,吕筠,余灿清,裴培,杜怀东,陈君石,陈铮鸣,李立明,孙点剑一,代表中国慢性病前瞻性研究项目协作组.中国10个地区成年男性Y染色体嵌合缺失流行病学分布及其与肺癌的前瞻性关联研究[J].Chinese journal of Epidemiology,2024,45(1):56-62

中国10个地区成年男性Y染色体嵌合缺失流行病学分布及其与肺癌的前瞻性关联研究

Epidemiological distribution of mosaic loss of chromosome Y in adult men in 10 areas in China and its prospective association with lung cancer

Received:April 12, 2023

DOI：10.3760/cma.j.cn112338-20230412-00228

KeyWord: Y染色体嵌合缺失流行病学分布肺癌前瞻性关联

English Key Word: Mosaic loss of chromosome Y Epidemiological distribution Lung cancer Prospective study

FundProject:国家自然科学基金（82103920，82192901，82192904，82192900，81941018）；国家重点研发计划（2020YFC2003405）；中国香港Kadoorie Charitable基金；英国Wellcome Trust（212946/Z/18/Z，202922/Z/16/Z，104085/Z/14/Z，088158/Z/09/Z）；英国医学研究理事会基金（MCPC_14135，MC_PC_13049）

Author Name	Affiliation	E-mail
Zhao Yuxuan	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
Song Mingyu	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
Lyu Jun	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases(Peking University), Ministry of Education, Beijing 100191, China
Yu Canqing	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases(Peking University), Ministry of Education, Beijing 100191, China
Pei Pei	Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China
Du Huaidong	Medical Research Council Population Health Research Unit, University of Oxford, Oxford OX3 7LF, United Kingdom Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom
Chen Junshi	China National Center for Food Safety Risk Assessment, Beijing 100022, China
Chen Zhengming	Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom
Li Liming	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases(Peking University), Ministry of Education, Beijing 100191, China
Sun Dianjianyi	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases(Peking University), Ministry of Education, Beijing 100191, China	dsun1@bjmu.edu.cn
for the China Kadoorie Biobank Collaborative Group

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Abstract:

目的描述和分析中国10个地区成年男性Y染色体嵌合缺失（mLOY）携带者流行病学分布特征，并探究mLOY与肺癌的前瞻性关联。方法数据来源于中国慢性病前瞻性研究项目基线调查（人口学特征、生活方式、体格指标等）、遗传分型及随访监测（截至2018年12月31日的健康结局），采用嵌合染色体变异工作流检测识别mLOY携带者，分年龄、地区、基线生活方式及疾病特征描述其流行病学分布特征，采用多因素logistic回归模型分析mLOY的影响因素，采用Cox比例风险回归模型探究mLOY和肺癌的前瞻性关联，在不同年龄段及不同吸烟状况人群中进行分层研究，并采用乘积分布法分析mLOY在吸烟与肺癌关联间潜在的中介作用。结果研究纳入42 859名成年男性，共检出2 458名mLOY携带者（检出率为5.7%），检出率随年龄增长而增加（P<0.05），城市地区检出率（7.3%±0.2%）高于农村地区（4.7%±0.1%），吸烟可能是mLOY检出的危险因素（OR=1.49，95%CI：1.36~1.64）。经过平均11.1年随访，共累计观察到1 041名肺癌新发病例，mLOY携带者新发肺癌的风险增加了24%（HR=1.24，95%CI：1.01~1.52），扩增性mLOY携带者（携带mLOY细胞分数≥10%）肺癌发生风险增加了50%（HR=1.50，95%CI：1.13~2.00），未发现年龄或吸烟状况的修饰效应作用（交互作用P>0.05）。mLOY在吸烟和肺癌关联中的中介效应显著，中介效应的点估计值（95%CI）为0.09（0.01~0.17）。结论我国10个地区成年男性mLOY检出率存在明显的社会人口经济学及生活方式分布差异，携带mLOY尤其是扩增性mLOY会显著增加肺癌的发病风险，且mLOY可能在吸烟与肺癌的关联中起中介作用。

English Abstract:

Objective To detect the prevalence of mosaic loss of chromosome Y in adult men in ten study areas in China, describe the epidemiological distribution of mosaic loss of chromosome Y (mLOY) carriers and assess its prospective association with lung cancer. Methods Based on the data from baseline survey, genetic analysis and follow-up (as of December 31, 2018) from China Kadoorie Biobank, we used Mosaic Chromosomal Alterations pipeline to detect mLOY carriers in 10 areas in China and described the epidemiological characteristics of mLOY carriers in adult men, including age, area distribution, lifestyle and disease history. We used multivariate logistic regression model to identify the potential relevant factor of mLOY. Cox proportional hazard regression model was fitted to assess the prospective association of mLOY with lung cancer. Stratification analysis were conducted to evaluate the potential modification effects of smoking and age. We also conducted mediation analysis to assess the mediating effect of mLOY in the association between smoking and lung cancer. Results A total of 42 859 adult men were included in our analysis, in whom 2 458 mLOY carriers were detected (5.7%). The detection rate increased with age (P<0.05). The detection rate was higher in urban area (7.3%±0.2%) than that in rural area (4.7%±0.1%). The results of logistic regression analysis indicated that smoking might be a risk factor for the detection of mLOY (OR=1.49, 95%CI:1.36-1.64). After follow-up for average 11.1 years, 1 041 lung cancer cases were observed. The prospective analysis showed that mLOY carriers had an increased risk for lung cancer by 24% compared with non-mLOY carriers (HR=1.24, 95%CI:1.01-1.52) and expanded mLOY carriers (mLOY cell proportion ≥10%) had an increased risk for lung cancer by 50% (HR=1.50, 95%CI:1.13-2.00). Stratification analysis showed no modification effects of smoking and age in the association between mLOY and lung cancer (interaction P>0.05). Mediation analysis showed that mLOY could be a mediating factor in the association between smoking and lung cancer, the estimated effect was 0.09 (0.01-0.17). Conclusions There were significant differences in the detection rate of mLOY in adult men with different social-economic characteristics and lifestyles in ten areas in China. Besides, mLOY carriers, especially expanded mLOY carriers, had increased risk for lung cancer and mLOY might be a mediating factor in the association between smoking and lung cancer.

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