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Components of the Risk Assessment Process

    continued...

    For relatives not affected with cancer, collect the following information:

    • Current age or age at death.
    • Cause of death (if deceased).
    • History of any surgeries or treatments that may have reduced the risk of cancer.
    • Cancer screening practices.
    • Any nonmalignant features associated with the syndrome in question.
    • Carcinogenic exposures.
    • Other significant health problems.

    Accuracy of the family history

    The accuracy of the family history has a direct bearing on determining the differential diagnoses, selecting appropriate testing, interpreting results of the genetic tests, refining individual cancer risk estimates, and outlining screening and risk reduction recommendations. In a telephone survey of 1,019 individuals, only 6% did not know whether a first-degree relative had cancer; this increased to 8.5% for second-degree relatives.[35] However, people often have incomplete or inaccurate information about the cancer history in their family.[31,32,34,36,37,38,39,40,41] A population-based survey of 2,605 first- and second-degree relatives and confirmed proband reports of cancer diagnoses found that the accuracy of reported cancer diagnoses in relatives was low to moderate, while reports of no history of cancer were accurate.[41] Accuracy varies by cancer site and degree of relatedness.[41,42] Reporting of cancer family histories may be most accurate for breast cancer [41,43] and less accurate for gynecologic malignancies [41,43] and colon cancer.[41] Self-reported family histories may contain errors and, in rare instances, could be fictitious.[39,43,44] It is important to confirm the primary site of cancers in the family that will affect the calculation of hereditary predisposition probabilities and/or estimation of empiric cancer risks, especially if decisions such as risk-reducing surgery will be based on this family history.[44] The most reliable documentation of cancer histology is the pathology report. Verification of cancers can also be made through other medical records, tumor registries, or death certificates.

    It is also important to consider limited, missing, or questionable information when reviewing a pedigree for cancer risk assessment. It is more difficult to identify features of hereditary disease in families with a truncated family structure due to loss of contact with relatives, small family size, or deaths at an early age from unrelated conditions. When there are few family members of the at-risk gender when considering a particular syndrome with primarily male or female specific disease manifestations, the family history may be difficult to assess (e.g., few female members in a family at risk of hereditary breast and ovarian cancer syndrome). In addition, information collected on risk-reducing surgical procedures, such as oophorectomy, could significantly change prior probability estimation and the constellation of cancers observed in a family.[45] Other factors to clarify and document whenever possible are adoptions, use of donor egg or sperm, consanguinity, and uncertain paternity.

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