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Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African-American men: the Flint Men's Health Study.

ABSTRACT: Association studies have examined the significance of several candidate genes based on biological pathways relevant to prostate carcinogenesis, including both the androgen and insulin-like growth factor pathways. Clinical and epidemiologic evidence suggest that androgens, specifically testosterone and dihydrotestosterone (DHT) are important not only in normal prostate growth but in the pathogenesis of prostate cancer. Similarly, the insulin-like growth factor-1 (IGF-1) signaling pathway regulates both cellular proliferation and apoptosis. Therefore, genes involved in the biosynthesis, activation, metabolism and degradation of androgens and the stimulation of mitogenic and antiapoptotic activities of prostate epithelial cells represent important candidates for affecting the development and progression of prostate cancer.Using resources from the Flint Men's Health Study, a population-based case control study of African-American men aged 40-79, we evaluated the associations between selected single-nucleotide polymorphisms (SNPs) in the CYP17, CYP3A4, CYP19A1, SDR5A2, IGF1, and IGFBP3 genes and prostate cancer diagnosis in 473 men (131 prostate cancer cases and 342 disease-free controls).We found a significant association between prostate cancer and selected CYP17 SNP genotypes, with the heterozygous genotype conferring decreased risk. Suggestive evidence for association between IGF1 SNPs and prostate cancer were also found. No significant associations were observed between SNPs in the other genes and prostate cancer.These findings suggest that variation in or around CYP17 and/or IGF1 may be associated with prostate cancer development in the African-American population. Additional studies are needed to determine whether these polymorphisms are indeed associated with prostate cancer risk in African Americans.

SUBMITTER: Sarma AV

PROVIDER: S-EPMC2712831 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African-American men: the Flint Men's Health Study.

Sarma Aruna V AV Dunn Rodney L RL Lange Leslie A LA Ray Anna A Wang Yunfei Y Lange Ethan M EM Cooney Kathleen A KA

The Prostate 20080201 3

<h4>Background</h4>Association studies have examined the significance of several candidate genes based on biological pathways relevant to prostate carcinogenesis, including both the androgen and insulin-like growth factor pathways. Clinical and epidemiologic evidence suggest that androgens, specifically testosterone and dihydrotestosterone (DHT) are important not only in normal prostate growth but in the pathogenesis of prostate cancer. Similarly, the insulin-like growth factor-1 (IGF-1) signali ...[more]

PMID: 18163429

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Project description:The American Men's Internet Survey (AMIS) is an annual Web-based behavioral survey of men who have sex with men (MSM) who live in the United States. This Rapid Surveillance Report describes the fifth cycle of data collection (July 2017 to November 2017: AMIS 2017). The key indicators are the same as those previously reported for past AMIS cycles (December 2013 to May 2014: AMIS 2013; November 2014 to April 2015: AMIS 2014; September 2015 to April 2016: AMIS 2015; and September 2016 to February 2017: AMIS 2016). The AMIS methodology has not substantively changed since AMIS 2016. The MSM were recruited from a variety of websites using banner advertisements and email blasts. Additionally, participants from AMIS 2016 who agreed to be recontacted for future research were emailed a link to AMIS 2017. Men were eligible to participate if they were aged ?15 years, resided in the United States, provided a valid US zone improvement plan code, and reported ever having sex with a man or identified as gay or bisexual. The analysis was limited to those who reported having oral or anal sex with a male partner in the past 12 months. We examined demographic and recruitment characteristics using multivariable regression modeling (P<.05) stratified by the participants' self-reported HIV status. The AMIS 2017 round of data collection resulted in 10,049 completed surveys from MSM representing every US state, Puerto Rico, and Guam. Participants were mainly non-Hispanic white, over the age of 40 years, living in the Southern United States and urban areas, and recruited from geospatial social networking websites. The plurality (4485/10,049, 44.6%) of participants was in the 40 years and older age group, followed by the youngest age group, 15 to 24 years (2726/10,049, 27.1%). Self-reported HIV prevalence was 9.6% (964/10,049). Compared with HIV-negative or unknown-status participants, HIV-positive participants were more likely to have had anal sex without a condom with a male partner in the past 12 months (adjusted odds ratio [aOR] 2.21, 95% CI 1.86-2.63) and more likely to have had anal sex without a condom with a serodiscordant or an unknown-status partner (aOR 3.13, 95% CI 2.71-3.62). The reported use of marijuana in the past 12 months was higher among HIV-positive participants than HIV-negative or unknown status participants (aOR 1.29, 95% CI 1.09-1.51). The reported use of methamphetamines and other illicit substances in the past 12 months was higher among HIV-positive participants than HIV-negative or unknown status participants (aOR 5.57, 95% CI 4.38-7.09 and aOR 1.93, 95% CI 1.65-2.27, respectively). Most HIV-negative or unknown status participants (7330/9085, 80.7%) reported ever taking an HIV test previously, and 60.6% (5504/9085) reported undergoing HIV testing in the past 12 months. HIV-positive participants were more likely to report testing and diagnosis of sexually transmitted infections than HIV-negative or unknown status participants (aOR 2.85, 95% CI 2.46-3.31 and aOR 2.73, 95% CI 2.29-3.26, respectively).

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Dataset Information

Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African-American men: the Flint Men's Health Study.

Publications

Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African-American men: the Flint Men's Health Study.

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