Luteinizing hormone beta polymorphism and risk of familial and sporadic prostate cancer.

Abstract

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-beta protein, LH-betaV, 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-betaV 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-betaV: 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-beta 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-beta 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-beta variant is a weak risk factor for prostate cancer.

• Authors: David A Elkins, Akira Yokomizo, Stephen N Thibodeau, Daniel J Schaid, Julie M Cunningham, Angela Marks, Eric Christensen, Shannon K McDonnell, Susan Slager, Brett J Peterson, Steven J Jacobsen, James R Cerhan, Michael L Blute, Donald J Tindall, Wanguo Liu
• Journal: The Prostate (Prostate) Vol. 56 Issue 1 Pg. 30-6 (Jun 15 2003) ISSN: 0270-4137 [Print] United States
• PMID: 12746844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Luteinizing Hormone, beta Subunit
• Prostate-Specific Antigen

Topics

• Adult
• Aged
• Aged, 80 and over
• Family Health
• Genetic Predisposition to Disease (epidemiology)
• Genotype
• Humans
• Luteinizing Hormone, beta Subunit (genetics)
• Male
• Middle Aged
• Polymorphism, Genetic
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (epidemiology, genetics)
• Risk Factors