Luteinizing hormone beta polymorphism and risk of familial and sporadic prostate cancer.
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.
Elkins
David A
DA
Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Yokomizo
Akira
A
Thibodeau
Stephen N
SN
J  Schaid
Daniel
D
Cunningham
Julie M
JM
Marks
Angela
A
Christensen
Eric
E
McDonnell
Shannon K
SK
Slager
Susan
S
J  Peterson
Brett
B
J  Jacobsen
Steven
S
R  Cerhan
James
J
L  Blute
Michael
M
J  Tindall
Donald
D
Liu
Wanguo
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors
D037101:Luteinizing Hormone, beta Subunit; D017430:Prostate-Specific Antigen