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

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.)

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