Macrophage Scavenger Receptor 1 999C>T (R293X) Mutation and Risk of Prostate Cancer

doi:10.1158/1055-9965.EPI-04-0202

Macrophage Scavenger Receptor 1 999C>T (R293X) Mutation and Risk of Prostate Cancer

Questa Hope1,
Sarah Bullock1,
Christopher Evans3,
Julia Meitz1,
Nancy Hamel4,
Stephen M. Edwards1,
Gianluca Severi9,15,
David Dearnaley1,
Sameer Jhavar1,
Christine Southgate1,
Alison Falconer1,
Anna Dowe1,
Kenneth Muir10,
Richard S. Houlston2,
James C. Engert6,
David Roquis7,
Daniel Sinnett8,
Jacques Simard11,
Ketil Heimdal12,
Pål Møller12,
Lovise Maehle12,
Michael Badzioch13,
Rosalind A. Eeles1,
Douglas F. Easton3,
Dallas R. English15,
Melissa C. Southey14,
John L. Hopper14,
William D. Foulkes5,
Graham G. Giles15 and
The Cancer Research UK/British Association of Urological Surgeons' Section of Oncology Collaborators

¹Translational Cancer Genetics Team, Section of Cancer Genetics and Urology Unit, Male Urological Centre and Institute of Cancer Research and Royal Marsden NHS Trust; ²Molecular and Population Genetics Team, Section of Cancer Genetics, Institute of Cancer Research, Surrey, United Kingdom; ³Cancer Research UK Genetic Epidemiology Unit, Strangeways Laboratories, University of Cambridge, Cambridge, United Kingdom; ⁴Research Institute of the McGill University Health Centre, ⁵Program in Cancer Genetics, Departments of Oncology and Human Genetics, and ⁶Mike Rosenbloom Laboratory for Cardiovascular Research, Division of Cardiology, Faculty of Medicine, McGill University; ⁷Centre d'Innovation Génome Québec et Université McGill, Plate-forme Sequencage; ⁸Centre de Cancérologie Charles Bruneau, Centre de Recherche de l'Hôpital Sainte-Justine, Département de Pédiatrie, Université de Montréal, Montréal, Québec, Canada; ⁹Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; ¹⁰Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom; ¹¹Cancer Genomics Laboratory, CHUL Research Centre, Sainte-Foy, Quebec, Canada; ¹²Section of Genetic Counselling, Department of Cancer Genetics, Norwegian Radium Hospital, Oslo, Norway; ¹³Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington; ¹⁴Centre for Genetic Epidemiology, Department of Public Health, University of Melbourne; and ¹⁵Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria, Australia

Requests for reprints:
William D. Foulkes, Program in Cancer Genetics, Room L10-120, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4. Phone: 514-934-1934-44121; Fax: 1-514-934-8273. E-mail: william.foulkes{at}mcgill.ca

Abstract

Background: Variants in the gene encoding the macrophage scavenger receptor 1 (MSR1⁴) protein have been identified in men with prostate cancer, and several small studies have suggested that the 999C>T (R293X) protein-truncating mutation may be associated with an increased risk for this disease.

Methods: Using large case-control, cohort, and prostate cancer family studies conducted in several Western countries, we tested for the 999C>T mutation in 2,943 men with invasive prostate carcinoma, including 401 males from multiple-case families, 1,982 cases unselected for age, and 575 men diagnosed before the age of 56 years, and in 2,870 male controls. Risk ratios were estimated by unconditional logistic regression adjusting for country and by a modified segregation analysis. A meta-analysis was conducted pooling our data with published data.

Results: The prevalence of MSR1*999C>T mutation carriers was 0.027 (SE, 0.003) in cases and 0.022 (SE, 0.002) in controls, and did not differ by country, ethnicity, or source. The adjusted risk ratio for prostate cancer associated with being a 999C>T carrier was 1.31 [95% confidence interval (CI), 0.93-1.84; P = 0.16]. The modified segregation analysis estimated the risk ratio to be 1.20 (95% CI, 0.87-1.66; P = 0.16). The risk ratio estimated from the meta-analysis was 1.34 (95% CI, 0.94-1.89; P = 0.10).

Conclusion: Our large-scale analysis of case and controls from several countries found no evidence that the 999C>T mutation is associated with increased risk of prostate cancer. The meta-analysis suggests it is unlikely that this mutation confers more than a 2-fold increased risk.

Footnotes

Grant support: U.S. Army grant DAMD17-00-1-0033 and the Canadian Genetic Diseases Network (W.D. Foulkes); NIH grant U01 CA89600 (W.D. Foulkes, R.A. Eeles, G.G. Giles, D.F. Easton, and J.L. Hopper), The Prostate Cancer Charitable Trust, Times Christmas Appeal, Institute of Cancer Research, Cancer Research UK, BREAKTHROUGH Breast Cancer, and a legacy of the late Marion Silcock (R.A.Eeles); National Health and Medical Research Council grant 126402 (J.L. Hopper); Tattersall's and the Whitten Foundation, the Cancer Council Victoria, National Health and Medical Research Council grant 20905, VicHealth grant 1999-0227 (J.L. Hopper and G.G. Giles); and Fonds de la recherche en Santé du Québéc Network of Applied Genetic Medicine (D. Sinnett and J. Simard).
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Note: Q. Hope, S. Bullock, and C. Evans contributed equally to this work. J. Simard holds a Canada Research Chair in Oncogenetics and D.F. Easton is a Principal Research Fellow of Cancer Research UK. K. Heimdal is currently in the Department of Medical Genetics, Rikshopitalet, University Hospital, Oslo, Norway. The list of Cancer Research UK/British Association of Urological Surgeons' Section of Oncology Collaborators are available on request.
- Accepted September 3, 2004.
- Received March 15, 2004.
- Revision received July 6, 2004.