Cost analysis of DNA‐based testing in a large Canadian family with multiple endocrine neoplasia type 2

Abstract

One of the major goals of genetic testing is the reduction of morbidity and mortality. Given the appropriate circumstances, this can result in reduction in health care costs. Such savings can be demonstrated most effectively in large families with mutations in well characterized, dominantly acting genes. In our large family, a point mutation TGC>CGC in exon 10 of the RET proto-oncogene, which results in a missense mutation (Cys620Arg), was identified in two individuals. The proband has medullary thyroid carcinoma (MTC), as did her deceased mother. One son has MTC and Hirschsprung's disease. The proband's mother had nine siblings; the proband has three siblings, another son, and 69 maternal cousins. Genetic testing has been performed on the closest relatives and has identified four individuals with, and 54 individuals without, a familial RET mutation. Significant cost savings have been realized in both genetic testing and clinical surveillance. In this family, for every at-risk individual identified as a true-negative, the minimum yearly savings in clinical surveillance is 508 dollars per person. As demonstrated by this case, economic costs of genetic diagnostics should take into account the potential saved monies in tests, both molecular and clinical.

Familial prevalence and age of RET germline mutations: implications for screening

“…Our current data, supported by the ‘advance’ of the Y791F RET germline mutation, emphasize the dire need of routinely testing every patient with medullary thyroid cancer for germline mutations, including all relevant RET exons (10, 11, 13, 14, 15 and 16). Shown to be cost‐effective, 36 this systematic approach must be implemented in full if one does not want to become lost in transition.…”

Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities

“…Barring sample mix‐up, DNA‐based screening of asymptomatic individuals for RET germline mutations affords unambiguous clarification of RET status, which is clearly superior to biochemical screening in terms of both accuracy and speed (reviewed in Machens and Dralle [62]). In clinical practice, DNA‐based screening was shown to be cost‐effective [63]. Based on the pooled data of 356 RET families from Germany (141 families), France (97 families), Italy (69 families), Poland (27 families) and Czech Republic (22 families), germline mutations in continental Europe [51, 64–68] (Table 1) involve codon 634 (41.0%), followed by codons 804 (11.8%), 918 (9.6%), 620 (8.4%), 618 and 790 (6.2% each), 791 and 891 (4.8% each), 768 (2.2%), 609 (2.0), 611 (1.4%), 630 (1.1), 631 and 883 (0.3% each).…”