Variantes genéticas comunes en las predicciones de riesgo de cáncer de próstata.

Background: One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age. Methods: We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data. Results: The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile). Conclusions: Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening.Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.

Autores : Lindstroem, S.; Schumacher, F.R.; Cox, D.; Travis, R.C.; Albanes, D.; Allen, N.E.; Andriole, G.; Berndt, S.I.; Boeing, H.; Bueno-de-Mesquita, H.B.; Crawford, E.D.; Diver, W.R.; Gaziano, J.M.; Giles, G.G.; Giovannucci, E.; Gonzalez, C.A.; Henderson, B.; Hunter, D.J.; Johansson, M.; Kolonel, L.N.; Ma, J.; Le Marchand, L.; Pala, V.; Stampfer, M.; Stram, D.O.; Thun, M.J.; Tjonneland, A.; Trichopoulos, D.; Virtamo, J.; Weinstein, S.J.; Willett, W.C.; Yeager, M.; Hayes, R.B.; Severi, G.; Haiman, C.A.; Chanock, S.J.; Peter, K.

Direcciones :

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2. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

3. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

4. Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02115 USA

5. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA

6. Harvard Univ, Sch Med, Boston, MA 02115 USA

7. Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA

8. Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA USA

9. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

10. INSERM, U1052, Ctr Leon Berard, Canc Res Ctr Lyon, F-75654 Paris 13, France

11. Int Agcy Res Canc, Lyon, France

12. Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Med, London SW7 2AZ, England

13. Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England

14. Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

15. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

16. Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA

17. Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany

18. Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands

19. Univ Med Ctr Utrecht UMCU, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

20. Univ Colorado, Hlth Sci Ctr, Denver, CO USA

21. Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

22. Univ Melbourne, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic 3010, Australia

23. Univ Melbourne, Ctr Mol Genet Environm & Analyt Epidemiol, Melbourne, Vic 3010, Australia

24. Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia

25. Catalan Inst Oncol IDIBELL RETICC RD06 0020, Unit Nutr Environm & Canc, Barcelona, Spain

26. Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden

27. Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA

28. Ist Nazl Tumori, Fdn IRCCS, Nutr Epidemiol Unit, Dept Predict Med, I-20133 Milan, Italy

29. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark

30. Acad Athens, Bur Epidemiol Res, Athens, Greece

31. Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland

32. NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA