title: All in the family? Analyzing the impact of family history in addition to genotype on medullary thyroid carcinoma aggressiveness in MEN2A patients.
abstract: Several guidelines for patients with multiple endocrine neoplasia 2A (MEN2A) take into account genotype and family history of medullary thyroid carcinoma (MTC) disease aggressiveness. We sought to determine if an association exists independent of genotype, which could provide important information for counseling MEN2A patients in management of their MTC. Pedigrees of patients with ≥5 family members with MEN2A were retrospectively reviewed. Analysis was performed among kindreds with the most frequently observed codon mutation (RET 634). Familial MTC disease aggressiveness was evaluated using: (1) mean age at diagnosis of MTC, (2) current mean age of carriers without MTC, (3) proportion of kindred with MTC with metastatic disease at diagnosis, (4) proportion of kindred with MTC with metastasis/death from MTC as worst outcome, and (5) proportion of kindred with disease progression. 170 affected patients from 12 different MEN2A kindreds met inclusion criteria. The number of affected family members available for study per kindred ranged from 8 to 43 individuals. A difference in mean age of MTC diagnosis was found in screened patients (p = 0.01); mean age of MTC-free patients did not differ (p = 0.93). No differences were noted among kindreds in disease stage at presentation, worst outcome, or progression; marked variation in these measures was noted within families. In conclusion, a difference in age of MTC diagnosis among different RET 634 kindreds was identified. In contrast, notable intra-familial variability in disease aggressiveness was observed. Based on these findings, we recommend counseling patients with codon 634 mutations that their MTC disease course cannot be predicted by that of their relatives.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Long
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Etzel
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Thereasa
authors.initials: T
authors.lastname: Rich
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hyde
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Perrier
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Graham
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Mimi I
authors.initials: MI
authors.lastname: Hu
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Cote
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Gagel
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA. eggrubbs@mdanderson.org.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Grubbs
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018276:Carcinoma, Medullary / Q000151:congenital* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003376:Counseling; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D055815:Young Adult
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Aggressive; Family history; Hereditary; Medullary thyroid carcinoma; Multiple endocrine neoplasia 2