title: IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans.
abstract: Insulin-like growth factor (IGF)-1 and Insulin-like growth factor binding protein-3 (IGFBP-3) are strong inhibitors of apoptosis and play a role in mediating the effects of growth hormone. Both IGF-1 and IGFBP-3 serum levels have been linked to cancer risk. Here, we explore the relationship between three common IGF polymorphisms [C/T single-nucleotide polymorphism (SNP) (rs7965399) and a dinucleotide repeat (CA)n within the 5' regulatory region of the IGF-1 gene and the -202 A/C SNP in the IGFBP-3 gene], serum levels and prostate cancer (Pca) risk in 767 African-Americans enrolled in a clinic-based case-control study. IGF-1 and IGFBP-3 levels were measured using immunochemiluminometric assay and the three polymorphisms were typed for 401 Pca cases and 366 age- and ethnicity-matched controls. Multiple linear regression and multivariable unconditional logistic regression were used to test for associations between genotypes and circulating IGF levels and Pca risk, respectively. The presence of at least one copy of the IGFBP-3 -202 C allele was strongly associated with lower IGFBP-3 serum levels (3532 versus 3106 ng/ml; P = 0.008). We also observed a 2-fold increase in Pca risk for individuals homozygous for the IGFBP-3 -202 C allele [odds ratio = 2.4; 95% confidence interval = 1.2-4.8). Furthermore, IGF-1 (CA)19 genotypes were significantly associated with lower IGFBP-3 serum levels (P = 0.003). Our results reveal that variation in the 5'-untranslated region of the IGF-1 and IGFBP-3 genes may be influencing IGF serum levels and Pca risk in African-Americans and suggest a need to explore this variation across diverse populations. Our study adds clarity and further support to the previous findings, implicating serum IGFBP-3 levels and the IGFBP-3 -202 A/C SNP in prostate carcinogenesis.
authors.affiliation: Cancer Biology Program, Division of Biological Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Wenndy
authors.initials: W
authors.lastname: Hernandez
authors.forename: Cassandra
authors.initials: C
authors.lastname: Grenade
authors.forename: Eunice R
authors.initials: ER
authors.lastname: Santos
authors.forename: Carolina
authors.initials: C
authors.lastname: Bonilla
authors.forename: Chiledum
authors.initials: C
authors.lastname: Ahaghotu
authors.forename: Rick A
authors.initials: RA
authors.lastname: Kittles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000706:statistics & numerical data; D004219:District of Columbia / Q000453:epidemiology; D014644:Genetic Variation; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic; D001741:Black or African American
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D017430:Prostate-Specific Antigen