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

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

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.

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