Bhawna Dubey1, Maria Jackson2, Charnita Zeigler-Johnson3, Karthik Devarajan4, Rafael E Flores-Obando5, Norma McFarlane-Anderson6, Marshall Tulloch-Reid7, William Aiken8, Kevin Kimbro9, Dominique Reed10, LaCreis R Kidd10, Denise Gibbs1, Sudhir Kumar11, Camille Ragin1. 1. Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. 2. Department of Community Health and Psychiatry, University of West Indies, Kingston, Jamaica. 3. Division of Population Sciences, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. 4. Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. 5. Department of Physiology and Pharmacology, State University of New York, Downstate Health Science University, Brooklyn, New York, USA. 6. Department of Basic Medical Sciences, University of the West Indies, Kingston, Jamaica. 7. Caribbean Institute for Health Research, University of the West Indies, Kingston, Mona, Jamaica. 8. Department of Surgery Radiology, Anesthesia and Intensive Care, Section of Surgery, Faculty of Medical Sciences, University of the West Indies, Kingston, Jamaica. 9. Biomedical or Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina, USA. 10. Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA. 11. Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Abstract
BACKGROUND: Prostate cancer (PC) risk increases with African ancestry and a history of sexually transmitted infections (STIs). Also, single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes influence PC risk. This pilot study explores interactions between STIs and TLR-related SNPs in relation to PC risk among Jamaican men. METHODS: This case-control study evaluates two TLR related SNPs in 356 Jamaican men (194 controls and 162 cases) with or without history of STIs using stepwise penalized logistic regression in multivariable analyses. RESULTS: Age (odds ratio [OR] = 1.08; 95% confidence interval [CI]: 1.04-1>.12; p < .001) and IRF3_rs2304206 GG genotype (OR = 0.47; 95% CI: 0.29-0<.78; p = .003) modulated PC risk in people with history of STIs. In the population with no history of STIs, resulting interactions between risk factors did not survive correction for multiple hypothesis testing. CONCLUSION: Overall, an interaction between the IFR3_rs2304206 variant and a history of exposure to STIs leads to greater decrease of PC risk than the presence of polymorphic genotype alone. These findings are suggestive and require further validation. Identification of gene variants along with detection of lifestyle behaviors may contribute to identification of men at a greater risk of PC development in the population.
BACKGROUND:Prostate cancer (PC) risk increases with African ancestry and a history of sexually transmitted infections (STIs). Also, single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes influence PC risk. This pilot study explores interactions between STIs and TLR-related SNPs in relation to PC risk among Jamaican men. METHODS: This case-control study evaluates two TLR related SNPs in 356 Jamaican men (194 controls and 162 cases) with or without history of STIs using stepwise penalized logistic regression in multivariable analyses. RESULTS: Age (odds ratio [OR] = 1.08; 95% confidence interval [CI]: 1.04-1>.12; p < .001) and IRF3_rs2304206 GG genotype (OR = 0.47; 95% CI: 0.29-0<.78; p = .003) modulated PC risk in people with history of STIs. In the population with no history of STIs, resulting interactions between risk factors did not survive correction for multiple hypothesis testing. CONCLUSION: Overall, an interaction between the IFR3_rs2304206 variant and a history of exposure to STIs leads to greater decrease of PC risk than the presence of polymorphic genotype alone. These findings are suggestive and require further validation. Identification of gene variants along with detection of lifestyle behaviors may contribute to identification of men at a greater risk of PC development in the population.
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