Peter Tishler

Channing Laboratory

PLCO (Learn more about this study)

2006-0251

Jul 1, 2006

Intrafamilial Concordance of Age of Clinical Manifestations of Prostate Cancer

Hypothesis: Age at onset of clinical manifestations of prostate cancer is concordant among affected related family members. Key Questions: If one family member has prostate cancer: At what age was it ascertained? Do other first-degree relatives have prostate cancer? If so, At what age was it ascertained? What is the correlation for age at onset among affected first-degree relatives? Background: Many studies have documented the familial aggregation of manifest prostate cancer. In five studies of this familial aggregation among first-degree relatives, this familial aggregation ranged from 4.4% in Swedish dizygotic (DZ) twins to 22% in the Utah Population Database (1-5). At least some of this familial aggregation appears to be mediated via genetic factors (2). Clinical experience suggests that prostate cancer exists in several forms on the basis of virulence: a highly malignant form affecting young men (ages <60), in which familial aggregation is well documented; and a more desultory form usually affecting older individuals and often leading to major clinical manifestations very late in life if at all. The applicant is not aware of any study relating age at onset of disease in an index case to that in other family members in general populations of individuals with prostate cancer. If, in fact, familial aggregation obtains not only for disease but also for age at onset of disease, this information from an index case would be of great diagnostic and therapeutic significance to other male relatives. Study Design: We intend to examine these age relationships in several populations. One of these are the relatives of subjects of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Subjects completed a questionnaire listing the ages, relationships and cancer types of any first degree relatives (and half sibs). Of the 73,571 male subjects, 0.5% reported 2 or more subjects with prostate cancer, or 368 multiply affected families. We shall look for concordance of age at diagnosis of prostate cancer among these relatives, using appropriate univariate statistical means (e.g., correlation coefficients and their significance). Multivariate analyses can be used to factor out a few potentially confounding covariates (e.g., age of subject, date questionnaire completed, possibly other variables that may be available). Control correlations will be made with randomly "scrambled" families. Progress Report: We have worked with PLCO investigators to design a database of information that is relevant to our study. This (deidentified) information, which is based on index cases who had >2 relatives with prostate cancer, has been sent to and established in our computer at the Channing Laboratory. A biostatistician, Wei Wang, Ph. D., joined the Channing in the fall of 2006, and will be analyzing the PLCO prostate cancer families in the near future. References: 1. Gronberg H, Damber L and Damber J-E. Studies of genetic factors in prostate cancer in a twin population. J Urol 1994; 152:1484-9. 2. Page WF, Braun MM, Partin AW, Caporaso N and Walsh P. Heredity and prostate cancer: a study of World War II veteran twins. The Prostate 1997; 33:240-5. 3. Ghadirian P, Howe GR, Hislop TG and Maisonneuve P. Family history of prostate cancer: a multi-center case-control study in Canada. Int J Cancer 1997: 70:679-81. 4. Gronberg H, Wiklund F and Damber J-E. Age specific risks of familial prostate carcinoma. Cancer 1999; 86:477-83. 5. Goldgar DE, Easton DF, Cannon-Albright LA and Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Nat Cancer Inst 1994; 86:1600-8. 6. Lichtenstein P, Holm NV, Verkasalo PK, Iladou A, et al. Environmental and heritable factors in the causation of cancer. Analyses of cohorts of twins from Sweden, Denmark, and Finland. New Eng J Med 2000; 343:78-85.