Fine-mapping IGF1 and prostate cancer risk in African Americans: The Multiethnic Cohort Study
Menée aux Etats-Unis auprès de 1 000 cas et 991 témoins issus d'une grande cohorte multiethnique, cette étude évalue l'association entre des polymorphismes du gène IGF1 et le risque de cancer de la prostate chez les hommes d'origine afro-américaine
Genetic variation at 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 156kb region of IGF1 in 80 African American aggressive prostate cancer cases. 334 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 (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.