Prediction of lung cancer risk in a Chinese population using a multifactorial genetic model

Author:

Li Huan,Yang Lixin,Zhao Xueying,Wang Jiucun,Qian Ji,Chen Hongyan,Fan Weiwei,Liu Hongcheng,Jin Li,Wang Weimin,Lu Daru

Abstract

Abstract Background Lung cancer is a complex polygenic disease. Although recent genome-wide association (GWA) studies have identified multiple susceptibility loci for lung cancer, most of these variants have not been validated in a Chinese population. In this study, we investigated whether a genetic risk score combining multiple. Methods Five single-nucleotide polymorphisms (SNPs) identified in previous GWA or large cohort studies were genotyped in 5068 Chinese case–control subjects. The genetic risk score (GRS) based on these SNPs was estimated by two approaches: a simple risk alleles count (cGRS) and a weighted (wGRS) method. The area under the receiver operating characteristic (ROC) curve (AUC) in combination with the bootstrap resampling method was used to assess the predictive performance of the genetic risk score for lung cancer. Results Four independent SNPs (rs2736100, rs402710, rs4488809 and rs4083914), were found to be associated with a risk of lung cancer. The wGRS based on these four SNPs was a better predictor than cGRS. Using a liability threshold model, we estimated that these four SNPs accounted for only 4.02% of genetic variance in lung cancer. Smoking history contributed significantly to lung cancer (P < 0.001) risk [AUC = 0.619 (0.603-0.634)], and incorporated with wGRS gave an AUC value of 0.639 (0.621-0.652) after adjustment for over-fitting. This model shows promise for assessing lung cancer risk in a Chinese population. Conclusion Our results indicate that although genetic variants related to lung cancer only added moderate discriminatory accuracy, it still improved the predictive ability of the assessment model in Chinese population.

Publisher

Springer Science and Business Media LLC

Subject

Genetics(clinical),Genetics

Reference30 articles.

1. Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.

2. Li X, Hemminki K: Familial and second lung cancers: a nation-wide epidemiologic study from Sweden. Lung Cancer. 2003, 39: 255-263. 10.1016/S0169-5002(02)00535-4.

3. Jonsson S, Thorsteinsdottir U, Gudbjartsson DF, Jonsson HH, Kristjansson K, Arnason S, Gudnason V, Isaksson HJ, Hallgrimsson J, Gulcher JR, Amundadottir LT, Kong A, Stefansson K: Familial risk of lung carcinoma in the Icelandic population. JAMA. 2004, 292: 2977-2983. 10.1001/jama.292.24.2977.

4. McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S, Krokan HE, Skorpen F, Elvestad MB, Vatten L, Njolstad I, Axelsson T, Chen C, Goodman G, Barnett M, Loomis MM, et al: Lung cancer susceptibility locus at 5p15.33. Nat Genet. 2008, 40: 1404-1406. 10.1038/ng.254.

5. Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, Blondal T, Thorgeirsson TE, Thorleifsson G, Kristjansson K, Thorisdottir K, Ragnarsson R, Sigurgeirsson B, Skuladottir H, Gudbjartsson T, Isaksson HJ, Einarsson GV, Benediktsdottir KR, Agnarsson BA, Olafsson K, Salvarsdottir A, Bjarnason H, Asgeirsdottir M, Kristinsson KT, Matthiasdottir S, Sveinsdottir SG, et al: Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 2009, 41: 221-227. 10.1038/ng.296.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3