Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

Abstract

BackgroundEstrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer.ObjectiveWe investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry.MethodsIn Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsThe AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations.ConclusionsThese preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry.

“Catechol-O-methyltransferase gene Val158Met polymorphism and prostate cancersusceptibility”

“…In total cases, genotype percentage of GG, AG and AA was 34.13%, 49.01% and 16.86% respectively (Table 1). These studies were performed in different countries-France (Cussenot et al, 2007), Iran (Omrani et al, 2009), Japan (Suzuki et al, 2003(Suzuki et al, ,2007Tanaka et al, 2006), Turkey (Pazarbasi et al, 2013), UK (Low et al, 2006), USA (Nock et al,2006;Brureau et al, 2016;Tang et al, 2017) Meta-analysis: (Table 2).…”

Building a Network of Biological Resource Centers for Research Purposes in the Caribbean: Excellent Potential for Research into Public Health Diseases

“…As French territories, most studies conducted in Guadeloupe and/or Martinique are usually associated or compared to mainland France data. In recent years however, openings toward African countries were nevertheless observed; mainly for hematologic disease such as sickle cell anemia [21] and prostate cancer research [20] both highly prevalent in our population as well as in Africa.…”

The role of CYP17A1 in prostate cancer development: structure, function, mechanism of action, genetic variations and its inhibition

“…The reasons for the large ethnic differences might be explain by the observation that African-Americans experience earlier puberty, higher serum levels of total testosterone and a higher incidence of PCa (Loukola et al 2004). Most recently, Brureau et al (2016) have found that the A2 allele and the A2/A2 genotype are not associated with a significant risk of PCa in two different populations of African ancestry, namely an Afro-Caribbean population from the French West Indies and a native African population from the Democratic Republic of Congo.…”

“…A few epidemiologic studies have determined a positive association between this polymorphism and the Gleason score/clinical stage and serum PSA levels (Sobti et al 2006(Sobti et al , 2008 but many more conclusions are negative (Haiman et al 2001;Stanford et al 2002;Madigan et al 2003;Mononem et al 2006;Okugi et al 2006;Hamada et al 2007;Wright et al 2010;Risio et al 2011;Souiden et al 2011;Sivonova et al 2012;Yamada et al 2013;Han et al 2015;Henríquez-Hernández et al 2015;Brureau et al 2016;Song et al 2016). Some of the studies suggest that the CYP17A1 gene is a risk factor for PCa in males of advanced age (Souiden et al 2011;Song et al 2016).…”