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A Common Prostate Cancer Risk Variant 5 ' of Microseminoprotein-beta (MSMB) Is a Strong Predictor of Circulating beta-Microseminoprotein (MSP) Levels in Multiple Populations

Författare

  • Kevin M. Waters
  • Daniel O. Stram
  • Loic Le Marchand
  • Robert J. Klein
  • Camilla Valtonen-André
  • Mari T. Peltola
  • Laurence N. Kolonel
  • Brian E. Henderson
  • Hans Lilja
  • Christopher A. Haiman

Summary, in English

Background: beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer. Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P < 10(-8)), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 x 10(-6)), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Cancer Epidemiol Biomarkers Prev; 19(10); 2639-46. (C) 2010 AACR.

Publiceringsår

2010

Språk

Engelska

Sidor

2639-2646

Publikation/Tidskrift/Serie

Cancer Epidemiology Biomarkers & Prevention

Volym

19

Issue

10

Dokumenttyp

Artikel i tidskrift

Förlag

American Association for Cancer Research

Ämne

  • Cancer and Oncology

Status

Published

Forskningsgrupp

  • Clinical Chemistry, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1538-7755