Clinical

Usefulness of genetic testing depends on mutation carrier probability

SAN FRANCISCO, Jul 08 (Reuters) - Molecular genetic testing is uninformative in the vast majority of people, even those with familial cancers, but quantitative methods can predict for whom such testing will be informative, according to a presentation here at the American Cancer Society's Second National Conference on Cancer Genetics.

Dr. Patrice Watson of Creighton University in Omaha, Nebraska, contends: "The probability of a positive result [with BRCA1 and BRCA2 screening] varies from case to case and has a major impact on the cost-benefit ratio. The probability of a positive result depends on the sensitivity and specificity of the test, and the probability of carrying the mutation, which in turn depends on the family history of cancer, the personal history of cancer, age, and the population prevalence of the mutation."

To date, "...no simple rule that identifies a high prevalence subset has been found, except that affected members of those rare families with many closely related breast and/or ovarian cases diagnosed at early ages, are likely to carry a mutation," the researcher noted. For "less obvious families," Dr. Watson said that complicated rules taking into account many aspects of family history and other risk factors need to be applied to determine the merits of genetic screening.

"A very similar situation exists with regard to HNPCC" and genetic screening for colorectal cancer, Dr. Watson said. "There has not yet been extensive mutation testing of the general population of colorectal cancer cases, nor modeling of prior probabilities comparable to what has been done in BRCA1 and BRCA2," she said, adding that while the specificity for the test is high, the sensitivity of HNPCC testing is inadequate for widespread screening.

"Based on the scanty data available...cases with a low prior probability will benefit little from testing. Prior probability has not been modeled yet but clearly depends greatly on family history. Personal history may also be important, including MSI status of tumor, age at diagnosis, site of cancers and other tumors."

Genetic testing can be useful, Dr. Watson commented, but, "the informativeness of the test depends on the prior probability of being a mutation carrier."

-Westport Newsroom 203 319 2700 -Story by Sandra Katzman