Abstract
Background:
Chronic inflammation and obesity may contribute to the genesis or progression of BPH and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4 and RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG and TCF7L2), with BPH.
Methods:
BPH cases (N=568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications or symptomatic BPH (American Urological Association Symptom Index Score ⩾15). Controls were men who had not had BPH surgery, did not use BPH medications and whose symptom score was ⩽7. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.
Results:
None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G) and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ⩾4 had an increased BPH risk compared with those with ⩽1 (OR, 1.78; 95% CI, 1.10–2.89; Ptrend=0.006).
Conclusions:
SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.
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Acknowledgements
We appreciate the contributions of staff of the Johns Hopkins George W. Comstock Center for Public Health Research and Prevention in the conduct of the CLUE II study. Dr Lopez was supported by a National Research Service Award from the National Cancer Institute (T32 CA009314). This work was supported by the American Institute for Cancer Research, the National Institute of Aging (U01 AG18033), the National Cancer Institute (N01 CO12400) and the National Cancer Institute Prostate Cancer Specialized Program of Research Excellence (Career Development Award from P50 CA58236). Cancer incidence data have been provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Mental Health and Hygiene. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries (NPCR of the Centers for Disease Control and Prevention (CDC)) for the funds that helped support the availability of the cancer registry data.
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Lopez, D., Peskoe, S., Tsilidis, K. et al. Association of variants in genes related to the immune response and obesity with BPH in CLUE II. Prostate Cancer Prostatic Dis 17, 353–358 (2014). https://doi.org/10.1038/pcan.2014.36
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DOI: https://doi.org/10.1038/pcan.2014.36
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