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Luteinizing hormone β polymorphism and risk of familial and sporadic prostate cancer
Author(s) -
Elkins David A.,
Yokomizo Akira,
Thibodeau Stephen N.,
J. Schaid Daniel,
Cunningham Julie M.,
Marks Angela,
Christensen Eric,
McDonnell Shan K.,
Slager Susan,
J. Peterson Brett,
J. Jacobsen Steven,
R. Cerhan James,
L. Blute Michael,
J. Tindall Donald,
Liu Wanguo
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10220
Subject(s) - prostate cancer , endocrinology , medicine , prostate , genotype , testosterone (patch) , luteinizing hormone , cancer , population , hormone , biology , genetics , gene , environmental health
Background Circulating testosterone plays an important role in maintenance and growth of prostate cells. Luteinizing hormone (LH), secreted from the anterior pituitary, signals testicular Leydig cells to secrete testosterone. A genetic variant of the LH‐β protein, LH‐βV, exists in up to 40% of Caucasians and is more bioactive than the wild‐type protein. We hypothesized that genetically determined variation in LH function might affect susceptibility to prostate cancer via altered testosterone secretion. Methods We determined the frequency of the LH‐βV polymorphism (two linked polymorphisms: Trp 8 → Arg and Ile 15 → Thr) in familial prostate cancer patients (n = 446), in sporadic prostate cancer patients (n = 388), and in population‐based controls without prostate cancer (n = 510) to assess the role of this polymorphism in susceptibility to prostate cancer. Results A higher frequency of this variant genotype (LH‐βV: Arg 8 /Thr 15 ) was observed in familial prostate cancer patients (18.6%) than in controls (13.7%), and after taking into account the correlation of the familial cases and adjusting for age and body mass index (BMI), there was a weak positive association between the variant LH‐β genotype, and risk of familial prostate cancer (OR = 1.29; 95% CI 0.96–1.75). The sporadic case group was also slightly more likely to have a variant genotype (15.2%) compared to the controls (13.7%), and after adjustment for age and BMI, a similar association with this variant was found (OR = 1.33; 95% CI 0.86–02.07). Surgical cases showed a slightly stronger association for the variant LH‐β genotype compared to non‐surgical cases, but among the surgical cases there was little variability in risk across nodal status, stage, and tumor grade. Conclusions These data are consistent with the hypothesis that the LH‐β variant is a weak risk factor for prostate cancer. Prostate 56: 30–36, 2003. © 2003 Wiley‐Liss, Inc.