Endocrine-related cancer 2018 01 29() pii 10.1530/ERC-17-0514
There is evidence in the literature that some RET (REarranged during Transfection) variants commonly associated with multiple endocrine neoplasia type 2A (MEN2A) may be more frequent in certain European countries: p.L790F in Germany; p.Y791F in Poland; and p.V804 in France and Italy. This investigation of 189 German medullary thyroid cancer families was undertaken to explore the geographic epidemiology of these three RET variants, based on place of residence of the last common ancestor grouped by Roman and Slavic historic settlement areas. Significant associations were obtained for RET p.Y791F and the Slavic historic settlement area (17% vs. 6%; P = 0.018), and RET p.V804M (but not p.V804L/c.2410G>T) and the Roman historic settlement area (24% vs. 6%; P = 0.002). These associations remained statistically significant when the control group was modelled closer to the mutational profile of the respective RET variant. RET p.L790F/c.2370G>T (but not RET p.L790F/c.2370G>C) was more prevalent outside the historic Roman settlement area than inside it. This difference missed statistical significance (14% vs. 4%; P = 0.11), possibly because of the Germanic ancestral heritage of present-day Germany. There is a clear need for additional geographical epidemiological studies, in particular to clarify the putative ‘Germanic’ ancestral heritage of RET p.L790F/c.2370G>T.