首页|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

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

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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(RO=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mLYO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mLYO会显著增加肺癌的发病风险,且mYLO可能在吸烟与肺癌的关联中起中介作用.
Epidemiological distribution of mosaic loss of chromosome Y in adult men in 10 areas in China and its prospective association with lung cancer
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(RO=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(mLYO 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 mLYO carriers,had increased risk for lung cancer and mLOY might be a mediating factor in the association between smoking and lung cancer.

Mosaic loss of chromosome YEpidemiological distributionLung cancerProspective study

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

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北京大学公共卫生学院流行病与卫生统计学系,北京 100191

北京大学公众健康与重大疫情防控战略研究中心,北京,100191

重大疾病流行病学教育部重点实验室(北京大学),北京 100191

牛津大学医学研究委员会人口健康研究组,牛津OX3 7LF

牛津大学临床与流行病学研究中心纳菲尔德人群健康系,牛津OX3 7LF

国家食品安全风险评估中心,北京 100022

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Y染色体嵌合缺失 流行病学分布 肺癌 前瞻性关联

国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家重点研发计划中国香港 Kadoorie Charitable基金英国 Wellcome Trust项目英国 Wellcome Trust项目英国 Wellcome Trust项目英国 Wellcome Trust项目英国医学研究理事会项目英国医学研究理事会项目

82103920821929018219290482192900819410182020YFC2003405212946/Z/18/Z202922/Z/16/Z104085/Z/14/Z088158/Z/09/ZMCPC_14135MC_PC_13049

2024

10.3760/cma.j.cn112338-20230412-00228

中华流行病学杂志
中华医学会

中华流行病学杂志

CSTPCD北大核心
影响因子：1.985
ISSN：0254-6450
年,卷(期)：2024.45(1)
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