Identification of Genes Associated With Cancer in Patients and Siblings Who Have Cancer

RATIONALE: Identification of genes that may be associated with developing certain types of cancer may someday provide important information about a person's risk of getting cancer. PURPOSE: This clinical trial is studying to see if certain genes may be associated with cancer in patients with cancer of the breast, prostate, lung, or colon and siblings of these patients.

OBJECTIVES: Gather allele-sharing statistics at approximately 100 candidate loci throughout the human genome most likely to influence genetic risk of cancer. Use these allele-sharing statistics to test the interaction of each locus individually with cancer-associated, rare alleles of HRAS1. Generalize this approach for one of four cancers (breast, colon, lung, or prostate), using allele-sharing statistics to test the interaction of each locus with every other locus. Replicate positive results in a distinct set of sibling pairs with cancer. Examine, when loci contributing to risk are detected, the influence of this genetic background on clinical outcomes, such as survival. OUTLINE: Each patient-sibling pair completes a family history questionnaire about the incidence of cancer in the family. Blood samples are obtained from both the patient and the sibling (and both living parents, if available). The blood samples are genotyped using approximately 300 micro-satellite markers flanking 100 candidate genes previously implicated in genetic risk for cancer. Certain loci are a priority due to their association with HRAS1: BRCA1 and all known mismatch repair loci; other repair genes, such as ATM; the Bloom's syndrome locus; and the XRCC group. Other genes are also mapped. Patients do not receive the results of the genetic testing and the results do not influence the type and duration of treatment. Patients only are followed annually. PROJECTED ACCRUAL: This study will accrue 1,000 patient-sibling pairs for breast cancer. After 18 months, another 1,000 patient-sibling pairs will be accrued for breast cancer. Therefore, up to 2,000 patient-sibling pairs will be accrued over 5 years. (Feasibility of accruing pairs for lung, colon, and prostate cancer is being assessed.)

stage I colon cancer, stage II colon cancer, stage III colon cancer, stage IV colon cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage III non-small cell lung cancer, limited stage small cell lung cancer, extensive stage small cell lung cancer, stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, stage IV prostate cancer, stage IV non-small cell lung cancer

DISEASE CHARACTERISTICS: Histologically confirmed colon, lung, prostate, or invasive breast cancer No ductal or lobular carcinoma in situ of the breast only Patient and natural full sibling must have (or have had) cancer of the same type Participants in E-3Y92 not eligible Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: Not specified Menopausal status: Not specified Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Larson GP, Ding Y, Cheng LS, Lundberg C, Gagalang V, Rivas G, Geller L, Weitzel J, MacDonald D, Archambeau J, Slater J, Neuberg D, Daly MB, Angel I, Benson AB 3rd, Smith K, Kirkwood JM, O'Dwyer PJ, Raskay B, Sutphen R, Drew R, Stewart JA, Werndli J, Johnson D, Ruckdeschel JC, Elston RC, Krontiris TG. Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT. Cancer Res. 2005 Feb 1;65(3):805-14.

Krontiris TG, Larson M, Weitzel JN, et al.: Mapping interactive cancer susceptibility loci: Eastern Cooperative Oncology Group. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A2147, 560a, 1998.