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Association between leptin receptor gene polymorphisms and early‐onset prostate cancer
Author(s) -
KoteJarai Z.,
Singh R.,
Durocher F.,
Easton D.,
Edwards S.M.,
ArdernJones A.,
Dearnaley D.P.,
Houlston R.,
Kirby R.,
Eeles R.
Publication year - 2003
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.2003.04272.x
Subject(s) - prostate cancer , apoptosis , programmed cell death , prostate , cancer , medicine , caspase , cancer research , gene , biology , endocrinology , genetics
Significant tissue loss is a consistent feature of ureteric obstruction with, most studies showing increased programmed cell death or apoptosis of kidney epithelial cells. The study by Chuang et al. showed that there is also muscular damage during obstruction, specifically of the ureteric myocytes. More importantly they show for the first time that this induction of cell death is associated with the increased expression of cytochrome c and the caspases, key proteins that drive the induction of apoptosis. Admittedly they do not show whether cytochrome c is released from the mitochondria or that the caspases are truly activated, important events in the cell death pathway, but an increase in their expression does indicate their role in this process. Understanding the pathways leading to tissue loss during ureteric obstruction has important implications in the development of novel treatments for this condition.OBJECTIVE To report a case‐control study examining the relationship between polymorphisms in the leptin receptor ( OBR ) gene and the development of young‐onset prostate cancer, because epidemiological studies report that prostate cancer risk is associated with animal fat intake, and thus we investigated if this association occurs via this genetic mechanism. PATIENTS, SUBJECTS AND METHODS The Lys109Arg (OBR1) and Gln223Arg ( OBR2 ) polymorphisms in the coding region of OBR were studied in blood DNA from 271 patients with prostate cancer aged < 56 years at diagnosis and 277 geographically matched control subjects. Cases were collected through the Cancer Research UK/British Prostate Group Familial Prostate Cancer Study. Blood DNA was genotyped using the polymerase chain reaction and a restriction enzyme digest. RESULTS There was no statistically significant association between the OBR genotype and prostate cancer risk; men homozygous for 109Arg genotype had a slightly increased risk for prostate cancer, with a relative risk (95% confidence interval) of 1.36 (0.65–2.85), and those homozygous for the 223Arg allele had some reduction in prostate cancer risk, at 0.82 (0.58–1.26), but neither was statistically significant. CONCLUSION This case‐control study showed no significant association between leptin receptor gene polymorphisms and the risk of young‐onset prostate cancer, suggesting that genetic variations in OBR are unlikely to have a major role in the development of early‐onset prostate cancer in the UK.