title: Fine-mapping IGF1 and prostate cancer risk in African Americans: the multiethnic cohort study.
abstract: 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.
authors.affiliation: Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico. egiorgi@lanl.gov.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Giorgi
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.affiliation: Division of Genetic Basis of Human Disease, Translational Genomics Research Institute, Phoenix, Arizona. Systems Imagination Inc., Phoenix, Arizona.
authors.forename: Darin
authors.initials: D
authors.lastname: Taverna
authors.affiliation: School of Medicine, University of Virginia, Charlottesville, Virginia.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Turner
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Fredrick
authors.initials: F
authors.lastname: Schumacher
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Annette
authors.initials: A
authors.lastname: Lum-Jones
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Maarit
authors.initials: M
authors.lastname: Tirikainen
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Christian
authors.initials: C
authors.lastname: Caberto
authors.affiliation: Division of Genetic Basis of Human Disease, Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Cancer Prevention Institute of California, Fremont, California.
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006254:Hawaii; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D015141:Los Angeles; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D018426:SEER Program
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I