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

David A. Elkins, Akira Yokomizo, Stephen N Thibodeau, Daniel J Schaid, Julie M Cunningham, Angela Marks, Eric Christensen, Shannon K. McDonnell, Susan L Slager, Brett J. Peterson, Steven J. Jacobsen, James R Cerhan, Michael L. Blute, Donald J. Tindall, Wanguo Liu

Research output: Contribution to journalArticle

16 Citations (Scopus)

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-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: Trp8 → Arg and Ile15 → 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 rostate cancer. RESULTS. A higher frequency of this variant genotype (LH-βV: Arg8/Thr15) 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.

Original languageEnglish (US)
Pages (from-to)30-36
Number of pages7
JournalProstate
Volume56
Issue number1
DOIs
StatePublished - Jun 15 2003

Fingerprint

Luteinizing Hormone
Prostatic Neoplasms
Genotype
Testosterone
Body Mass Index
Familial Prostate cancer
Population Control
Leydig Cells
Prostate
Neoplasms
Proteins
Maintenance
Growth

Keywords

  • Luteinizing hormone
  • Polymorphism
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this

Luteinizing hormone β polymorphism and risk of familial and sporadic prostate cancer. / Elkins, David A.; Yokomizo, Akira; Thibodeau, Stephen N; Schaid, Daniel J; Cunningham, Julie M; Marks, Angela; Christensen, Eric; McDonnell, Shannon K.; Slager, Susan L; Peterson, Brett J.; Jacobsen, Steven J.; Cerhan, James R; Blute, Michael L.; Tindall, Donald J.; Liu, Wanguo.

In: Prostate, Vol. 56, No. 1, 15.06.2003, p. 30-36.

Research output: Contribution to journalArticle

Elkins, DA, Yokomizo, A, Thibodeau, SN, Schaid, DJ, Cunningham, JM, Marks, A, Christensen, E, McDonnell, SK, Slager, SL, Peterson, BJ, Jacobsen, SJ, Cerhan, JR, Blute, ML, Tindall, DJ & Liu, W 2003, 'Luteinizing hormone β polymorphism and risk of familial and sporadic prostate cancer', Prostate, vol. 56, no. 1, pp. 30-36. https://doi.org/10.1002/pros.10220
Elkins, David A. ; Yokomizo, Akira ; Thibodeau, Stephen N ; Schaid, Daniel J ; Cunningham, Julie M ; Marks, Angela ; Christensen, Eric ; McDonnell, Shannon K. ; Slager, Susan L ; Peterson, Brett J. ; Jacobsen, Steven J. ; Cerhan, James R ; Blute, Michael L. ; Tindall, Donald J. ; Liu, Wanguo. / Luteinizing hormone β polymorphism and risk of familial and sporadic prostate cancer. In: Prostate. 2003 ; Vol. 56, No. 1. pp. 30-36.
@article{70502c1b611144cfb689c5b1e8029e5f,
title = "Luteinizing hormone β 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-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: Trp8 → Arg and Ile15 → 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 rostate cancer. RESULTS. A higher frequency of this variant genotype (LH-βV: Arg8/Thr15) 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.",
keywords = "Luteinizing hormone, Polymorphism, Prostate cancer",
author = "Elkins, {David A.} and Akira Yokomizo and Thibodeau, {Stephen N} and Schaid, {Daniel J} and Cunningham, {Julie M} and Angela Marks and Eric Christensen and McDonnell, {Shannon K.} and Slager, {Susan L} and Peterson, {Brett J.} and Jacobsen, {Steven J.} and Cerhan, {James R} and Blute, {Michael L.} and Tindall, {Donald J.} and Wanguo Liu",
year = "2003",
month = "6",
day = "15",
doi = "10.1002/pros.10220",
language = "English (US)",
volume = "56",
pages = "30--36",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Luteinizing hormone β polymorphism and risk of familial and sporadic prostate cancer

AU - Elkins, David A.

AU - Yokomizo, Akira

AU - Thibodeau, Stephen N

AU - Schaid, Daniel J

AU - Cunningham, Julie M

AU - Marks, Angela

AU - Christensen, Eric

AU - McDonnell, Shannon K.

AU - Slager, Susan L

AU - Peterson, Brett J.

AU - Jacobsen, Steven J.

AU - Cerhan, James R

AU - Blute, Michael L.

AU - Tindall, Donald J.

AU - Liu, Wanguo

PY - 2003/6/15

Y1 - 2003/6/15

N2 - 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: Trp8 → Arg and Ile15 → 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 rostate cancer. RESULTS. A higher frequency of this variant genotype (LH-βV: Arg8/Thr15) 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.

AB - 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: Trp8 → Arg and Ile15 → 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 rostate cancer. RESULTS. A higher frequency of this variant genotype (LH-βV: Arg8/Thr15) 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.

KW - Luteinizing hormone

KW - Polymorphism

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=0038242421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038242421&partnerID=8YFLogxK

U2 - 10.1002/pros.10220

DO - 10.1002/pros.10220

M3 - Article

C2 - 12746844

AN - SCOPUS:0038242421

VL - 56

SP - 30

EP - 36

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 1

ER -