Disentangling the Babylonian speech confusion in genetic counseling: An analysis of the reliability and validity of the nomenclature for BRCA1/2 DNA-test results other than pathogenic

Abstract

Purpose: Effective communication of DNA-test results requires a sound terminology. However, the variety of terms in literature for DNA-test results other than pathogenic, may create inconsistencies between professionals, and misunderstanding in patients. Therefore, we conducted a theoretical and empirical analysis of the terms most frequently used in articles between 2002 and 2007 for BRCA 1/2-test results other than pathogenic.1 Design: We analyzed the content validity of the no-pathogenic DNA-test result-terms by comparing the literal and intended meaning of the terms and by examining their clarity and the inclusion of all relevant information. We analyzed the reliability of the terms by measuring the strength of association between terms and their meanings and the consistency among different authors over time. ecause more and more genes are being identified, several guidelines have been developed to standardize the naming and symbolization of genes, changes in genes, and protein sequences. Guidelines for human gene nomenclature were first published in 1979 and were later updated. 1 Several suggestions for further standardization have been made. 2-5 However, these guidelines only focused on naming changes in DNA and protein sequences. No guidelines have been developed for the communication of no-pathogenic DNA-test results (NPDTRs), i.e., when suspected pathogenic changes are not detected in mutation analysis in individual patients. Should we communicate such findings to patients as "negative," "no-pathogenic," or "uninformative"?These no-pathogenic DNA-test results (NPDTRs) are frequently found. For example, pathogenic mutations in the BRCA1 or BRCA2 genes for hereditary breast and ovarian cancer are only found in about 10% of tested probands from breast cancer families. In about 80% of all tested probands, no BRCA1/2 mutation is identified. In the remaining 10%, a BRCA1/2 variant, often a missense mutation, is detected for which the clinical significance regarding cancer risks is not known; future research may show this variant to be a diseasecausing mutation or a benign polymorphism.When a pathogenic BRCA1 mutation is found, lifetime cancer risks of 65% to 85% for breast and 39% to 69% for ovarian cancer are communicated to the counselee; when a pathogenic BRCA2 mutation is found, breast cancer risks of 45% to 84% and ovarian cancer risks of 11% to 27% are communicated. 6 -10 On the basis of these risks, possible risk management options are discussed, such as surveillance and prophylactic surgery of breasts and/or ovaries. However, in the NPDTR, decisions about surveillance and prophylactic surgery and DNA testing in relatives are based on the family pedigree and cancer history. 11 The communication of NPDTRs is often a difficult process because of the involvement of several groups of people. Molecular geneticists have to interpret DNA-test results correctly and convey these to clinicians. Subsequently, clinicians have to translate DNA-test results understandably to patients who have to recall DNA-tests ou...

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