Giorgi Elena E, Stram Daniel O, Taverna Darin, Turner Stephen D, Schumacher Fredrick, Haiman Christopher A, Lum-Jones Annette, Tirikainen Maarit, Caberto Christian, Duggan David, Henderson Brian E, Le Marchand Loic, Cheng Iona
Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico.
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1928-32. doi: 10.1158/1055-9965.EPI-14-0333. Epub 2014 Jun 5.
Genetic variation at insulin-like growth factor 1 (IGF1) has been linked to prostate cancer risk. However, the specific predisposing variants have not been identified. In this study, we fine-mapped the IGF1 locus for prostate cancer risk in African Americans. We conducted targeted Roche GS-Junior 454 resequencing of a 156-kb region of IGF1 in 80 African American aggressive prostate cancer cases. Three hundred and thirty-four IGF1 SNPs were examined for their association with prostate cancer risk in 1,000 African American prostate cancer cases and 991 controls. The top associated SNP in African Americans, rs148371593, was examined in an additional 3,465 prostate cancer cases and 3,425 controls of non-African American ancestry-European Americans, Japanese Americans, Latinos, and Native Hawaiians. The overall association of 334 IGF1 SNPs and prostate cancer risk was assessed using logistic kernel-machine methods. The association between each SNP and prostate cancer risk was evaluated through unconditional logistic regression. A false discovery rate threshold of q < 0.1 was used to determine statistical significance of associations. We identified 8 novel IGF1 SNPs. The cumulative effect of the 334 IGF1 SNPs was not associated with prostate cancer risk (P = 0.13) in African Americans. Twenty SNPs were nominally associated with prostate cancer at P < 0.05. The top associated SNP among African Americans, rs148371593 [minor allele frequency (MAF) = 0.03; P = 0.0014; q > 0.1], did not reach our criterion of statistical significance. This polymorphism was rare in non-African Americans (MAF < 0.003) and was not associated with prostate cancer risk (P = 0.98). Our findings do not support the role of IGF1 variants and prostate cancer risk among African Americans.
胰岛素样生长因子1（IGF1）的基因变异与前列腺癌风险相关。然而，具体的易感变异尚未确定。在本研究中，我们对非裔美国人中与前列腺癌风险相关的IGF1基因座进行了精细定位。我们对80例非裔美国人侵袭性前列腺癌病例的IGF1基因156 kb区域进行了靶向罗氏GS-Junior 454重测序。在1000例非裔美国人前列腺癌病例和991例对照中，检测了334个IGF1单核苷酸多态性（SNP）与前列腺癌风险的关联。在另外3465例前列腺癌病例和3425例非非裔美国人血统的对照（欧洲裔美国人、日裔美国人、拉丁裔和夏威夷原住民）中，检测了非裔美国人中最相关的SNP rs148371593。使用逻辑核机器方法评估334个IGF1 SNP与前列腺癌风险的总体关联。通过无条件逻辑回归评估每个SNP与前列腺癌风险的关联。使用错误发现率阈值q < 0.1来确定关联的统计学显著性。我们鉴定出8个新的IGF1 SNP。在非裔美国人中，334个IGF1 SNP的累积效应与前列腺癌风险无关（P = 0.13）。20个SNP在P < 0.05时与前列腺癌名义上相关。非裔美国人中最相关的SNP rs148371593[次要等位基因频率（MAF）= 0.03；P = 0.0014；q > 0.1]未达到我们的统计学显著性标准。这种多态性在非非裔美国人中罕见（MAF < 0.003），且与前列腺癌风险无关（P = 0.98）。我们的研究结果不支持IGF1变异在非裔美国人前列腺癌风险中的作用。
