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Case-control studies have established with little doubt that the etiology of papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) is heavily influenced by hereditary factors, ie, predisposing genes. In classic studies from Utah (1) and Sweden (2), the risk to first-degree relatives of probands was 8- and 12-fold, respectively, being among the highest of all cancers (3) and sharing the top rankings with multiple myeloma and testicular cancer, among others. One interesting observation in this regard is that none of the 3 above-mentioned cancers is known to occur often in large families. Typical pedigrees often do not evoke Mendelian inheritance but instead are small with irregular transmission of the cancer phenotype. Perhaps most importantly, in these cancers, no predisposing genes have yet been detected that account for anything but a tiny fraction of all familial or sporadic cases. In contrast, some other cancers such as colorectal, breast, and prostate cancers have a substantially lower degree of heritability/familiality as shown in case-control studies (2- to 4-fold enrichment in first-degree relatives), yet gene mutations such as the mismatch repair genes and the BRCA genes account for sizeable fractions of the disease phenotypes.

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