title: Comprehensive evaluation of genetic variation in the IGF1 gene and risk of prostate cancer.
abstract: Insulin-like growth factor-I (IGF1) stimulates cell proliferation, decreases apoptosis, and has been implicated in cancer development. Epidemiological studies have shown elevated levels of circulating IGF1 to be associated with increased risk of prostate cancer. To what extent genetic variation in the IGF1 gene is related to prostate cancer risk is largely unknown. We performed a comprehensive haplotype tagging (HT) assessment of single nucleotide polymorphisms (SNPs) representing the common haplotype variation in the IGF1 gene. We genotyped 10 SNPs (9 haplotype tagging SNPs (htSNPs)) within Cancer Prostate in Sweden (CAPS), a case-control study of 2,863 cases and 1,737 controls, in order to investigate if genetic variation in the IGF1 gene is associated with prostate cancer risk. Three haplotype blocks were identified across the IGF1 gene and 9 SNPs were selected as haplotype tagging SNPs. Common haplotypes in the block covering the 3' region of the IGF1 gene showed significant global association with prostate cancer risk (p = 0.004), with one particular haplotype giving an odds ratio of 1.46 (95% CI = 1.15-1.84, p = 0.002). This haplotype had a prevalence of 5% in the study population. Our results indicate that common variation in the IGF1 gene, particularly in the 3' region, may affect prostate cancer risk. Further studies on genetic variations in the IGF1 gene in relation to prostate cancer risk as well as to circulating levels of IGF1 are needed to confirm this novel finding.
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Catherine
authors.initials: C
authors.lastname: Boillot
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.forename: Katarina
authors.initials: K
authors.lastname: Bälter
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D013548:Sweden
chemical_list: D007334:Insulin-Like Growth Factor I