The changing incidence and spectrum of thyroid carcinoma in Tasmania (1978-1998) during a transition from iodine sufficiency to iodine deficiency.

Exposure to ionizing radiation, changing levels of iodine nutrition, and increased pathologic diagnosis of clinically unimportant thyroid neoplasia have all been proposed as explanations for a worldwide rise in the incidence of thyroid carcinoma (TC) over the past 6 decades. Tasmania is geographically an area of endemic iodine deficiency. In this report, we describe the spectrum of TC in a population averaging 450,000 persons during a 21-yr period that spans the communities transition from iodine sufficiency to iodine deficiency after discontinuation of universal iodine prophylaxis in the mid 1980s. The Tasmanian Cancer Register was used to ascertain all cases of TC diagnosed in Tasmania between 1978 and 1998. Histopathological and demographic data were reviewed. A total of 289 cases of TC were identified. Papillary TC (PTC), follicular TC, medullary TC, and other species accounted for 62%, 23%, 4%, and 11% of cases, respectively. The age standardized incidence rate for total TC increased from 2.45 to 5.33 per 100,000 for females and 0.75 to 1.76 per 100,000 for males between 1978 and 1984 and 1992 and 1998, respectively. A rise in the incidence of PTC by 4.5-fold (P < 0.05) in females and 2.1-fold in males (not significant) was the dominant change over this period. In parallel, the proportion of follicular TC relative to PTC fell from 0.35 to 0.17 during these years (P < 0.05). The rise in PTC incidence was, in part, due to an increase in the occurrence of tumors 1cm or less in diameter. Nonetheless, a 3-fold rise in incidence of larger lesions was also observed during the study period. Forty-three (24%) PTC cases had multifocal disease, 17 (40%) of whom had bilateral tumors. Familial (autosomal dominant) PTC was identified in nine (5%) total PTC cases. Prior studies have linked iodine prophylaxis to a rise in the proportion of differentiated TC, particularly PTC. Our data suggest a complex relationship between iodine nutrition and thyroid tumorigenesis. Factors such as a long latency between changes in iodine nutrition and thyroid tumorigenesis, a dose threshold for the effect of iodine nutrition on thyroid tumorigenesis, and an interaction between iodine nutrition and thyroidal sensitivity to ionizing radiation may all play a role.

Ca2+-dependent muscle dysfunction caused by mutation of the Caenorhabditis elegans troponin T-1 gene.

We have investigated the functions of troponin T (CeTnT-1) in Caenorhabditis elegans embryonic body wall muscle. TnT tethers troponin I (TnI) and troponin C (TnC) to the thin filament via tropomyosin (Tm), and TnT/Tm regulates the activation and inhibition of myosin-actin interaction in response to changes in intracellular [Ca2+]. Loss of CeTnT-1 function causes aberrant muscle trembling and tearing of muscle cells from their exoskeletal attachment sites (Myers, C.D., P.-Y. Goh, T. StC. Allen, E.A. Bucher, and T. Bogaert. 1996. J. Cell Biol. 132:1061-1077). We hypothesized that muscle tearing is a consequence of excessive force generation resulting from defective tethering of Tn complex proteins. Biochemical studies suggest that such defective tethering would result in either (a) Ca2+-independent activation, due to lack of Tn complex binding and consequent lack of inhibition, or (b) delayed reestablishment of TnI/TnC binding to the thin filament after Ca2+ activation and consequent abnormal duration of force. Analyses of animals doubly mutant for CeTnT-1 and for genes required for Ca2+ signaling support that CeTnT-1 phenotypes are dependent on Ca2+ signaling, thus supporting the second model and providing new in vivo evidence that full inhibition of thin filaments in low [Ca2+] does not require TnT.