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

Prostate. 2003 Jun 15;56(1):30-6. doi: 10.1002/pros.10220.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*
  • Prostatic Neoplasms / genetics*
  • Risk Factors


  • Luteinizing Hormone, beta Subunit
  • Prostate-Specific Antigen