文章摘要
朱猛,吕筠,余灿清,黄艳倩,马红霞,靳光付,郭彧,裴培,陈铮鸣,沈洪兵,胡志斌,李立明,代表中国慢性病前膽性研究项目协作组.多基因遗传风险评分指导肺癌个体化筛查的前瞻性队列研究[J].中华流行病学杂志,,():
多基因遗传风险评分指导肺癌个体化筛查的前瞻性队列研究
Polygenic risk score in personalized screening of lung cancer: a prospective cohort study in Chinese
收稿日期:2021-01-07  出版日期:2021-03-24
DOI:10.3760/cma.j.cn112338-20210107-00013
中文关键词: 多基因遗传风险评分;绝对发病风险;肺癌筛查;分子流行病学
英文关键词: Polygenic genetic risk score;Absolute risk;Lung cancer screening;Molecular epidemiology
基金项目:国家重点研发计划(2018YFC1315002);国家自然科学基金(81803306,81521004,81820108028,81573238);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)
作者单位E-mail
朱猛 南京医科大学公共卫生学院流行病学系 211166  
吕筠 北京大学公共卫生学院/北京大学公众健康与重大疫情防控战略研究中心 100191  
余灿清 北京大学公共卫生学院/北京大学公众健康与重大疫情防控战略研究中心 100191  
黄艳倩 南京医科大学公共卫生学院流行病学系 211166  
马红霞 南京医科大学公共卫生学院流行病学系 211166  
靳光付 南京医科大学公共卫生学院流行病学系 211166  
郭彧 中国医学科学院,北京 100730  
裴培 中国医学科学院,北京 100730  
陈铮鸣 英国牛津大学临床与流行病学研究中心纳菲尔德人群健康系 OX3 7LF  
沈洪兵 南京医科大学公共卫生学院流行病学系 211166  
胡志斌 南京医科大学公共卫生学院流行病学系 211166 zhibin_hu@njmu.edu.cn 
李立明 北京大学公共卫生学院/北京大学公众健康与重大疫情防控战略研究中心 100191 lmlee@bjmu.edu.cn 
代表中国慢性病前膽性研究项目协作组   
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中文摘要:
      目的 探索如何利用遗传风险评分,制订个体化的肺癌筛查方案。方法 利用中国慢性病前瞻性研究(CKB)队列10个地区100 615例具有全基因组基因分型信息的样本,根据前期课题组发表的19个遗传变异构建肺癌多基因遗传风险评分PRS-19。以55岁且吸烟剂量30包/年人群的5年绝对发病风险为参考届值,在吸烟者和非吸烟者中分别计算不同遗传风险人群5年肺癌绝对发病风险随年龄和吸烟剂量的变化趋势,并绘制5年绝对发病风险分布图,从而判断不同遗传风险人群达到参考界值时的理论年龄或吸烟剂量。根据上述结果给出不同遗传风险人群参加肺癌筛查起始年龄的具体建议。结果 CKB队列中55岁吸烟者,当吸烟量为30包/年时,5年内发生肺癌的绝对风险为0.67%。在吸烟者中,随着遗传风险增加,其5年绝对发病风险呈不断上升趋势,对于高遗传风险人群应降低筛查起始年龄,遗传风险最高的1%人群建议从50岁开始进行筛查;若保持筛查起始年龄55岁不变,则应在高遗传风险人群中降低吸烟剂量标准;不管累积吸烟剂量为多少,遗传风险最高的1%人群都应纳入肺癌筛查。在非吸烟者中,高遗传风险人群同样具备筛查价值,建议遗传风险最高的1%人群从62岁起进行肺癌筛查,而对于遗传风险最低的5%人群,当年龄达到74岁时才可达到参考届值。结论 对于不同遗传风险的个体,可采用个体化的肺癌筛查方案,对于高遗传风险的吸烟者可减小肺癌筛查起始年龄或吸烟剂量,而我国高遗传风险的非吸烟者同样具备筛查价值。
英文摘要:
      Objective To explore how to personalize lung cancer screening programs for prevention in Chinese populations based on individual genetic risk score. Methods We constructed the lung cancer polygenic genetic risk score (PRS-19) based on the 19 previously published genetic variations, using 100 615 participants with genotyping data from the China Kadoorie Biobank (CKB). Using the 5-year absolute risk of lung cancer in a population (55 years old with at least 30-pack-year history of smoking) as reference, the trend of 5-year absolute risk in different genetic risk groups was calculated in smokers and non-smokers, respectively. Distribution curves of 5-year absolute risk were also described to determine the theoretical age or smoking dose when different genetic risk groups reached the reference values. Given the overall findings, the specific start age for lung cancer screening were suggested for different genetic risk groups. Results The 5-year absolute risk of lung cancer was 0.67% in 55-year-old smokers with 30 packs per year in the CKB. Among smokers, 5-year absolute risk of participants increased as the genetic risk increased. Hence, it was recommended that people at high genetic risk should start screening earlier. For the highest genetic risk populations (the top 1% of PRS), the start age might be changed to 50 years old. If the start age remained at 55-year-old, the smoking dose should be set lowered in high genetic risk populations. For the highest genetic risk populations, they should be included in lung cancer screening regardless of the cumulative smoking exposure. Among nonsmokers, it was also valuable to screen people with high genetic risk, considering the start age of 62 for the highest genetic risk populations and 74 for the lowest genetic risk populations (the bottom 5% of PRS). Conclusions PRS-19 can be effectively used in developing lung cancer screening program for individualized prevention in China. For smokers with high genetic risk, the recommended starting age and smoking dose could be lowered for lung cancer screening, and non-smokers with high genetic risk could also be included in the screening programs.
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