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Medullary thyroid cancer and pheochromocytoma in MEN2A: are there parent of origin effects on disease expression?

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Abstract

There are no data on the impact of parent-of-origin effects on the expression of multiple endocrine neoplasia type 2A (MEN2A). The present study aimed to explore effects of parent-of-origin and offspring gender in MEN2A. In total, 224 carriers harbored heterozygous RET (REarranged during Transfection) p.Cys634 missense variants, for 169 of whom information on parent-of-origin gender was available. Altogether, offspring from affected fathers harbored more often node metastases from medullary thyroid cancer (45 vs. 19%; P = 0.006) and bilateral pheochromocytoma (24 vs. 10%; P = 0.021) than offspring from affected mothers. The former also also tended to be older at most recent follow-up (medians of 21 vs. 14 years; P = 0.056) and tended to have more often pheochromocytoma (33 vs. 19 yrs.; P = 0.051) and primary hyperparathyroidism (13 vs. 4%; P = 0.090) than the latter. Daughters from affected fathers harbored more often node metastases (39 vs. 15%; P = 0.043) than daughters from affected mothers. This difference decreased in male offspring when sons from affected fathers were compared with sons from affected mothers (52 vs. 40%; P = 0.111). There was also a slight deficit of male offspring: 1.1 sons each per affected mother and father vs. 1.2 daughters per affected mother and 1.4 daughters per affected father. These data suggest a parent-of-origin effect in MEN2A, warranting international collaborative research.

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Fig. 1

Data availability

The datasets used and analyzed during the current study are not publicly available due to privacy restrictions and are securely in the possession of the corresponding author, who has full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Code availability

Not applicable.

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Straße 40, 06097, Halle (Saale), Germany

    Andreas Machens, Kerstin Lorenz & Henning Dralle

  2. Department of General, Visceral and Transplantation Surgery, Section of Endocrine Surgery, University of Duisburg-Essen, 45122, Essen, Germany

    Frank Weber & Henning Dralle

Authors
  1. Andreas Machens
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  2. Kerstin Lorenz
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  3. Frank Weber
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  4. Henning Dralle
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Contributions

AM: Conceptualization, methodology, validation, formal analysis, investigation, writing—original draft. KL: Investigation, Writing—review & editing. FW: Investigation, Writing—review & editing. HD: Conceptualization, methodology, investigation, writing—review & editing, supervision.

Corresponding author

Correspondence to Andreas Machens.

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Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

Retrospective analysis of existing data sets from routine patient care does not require institutional review board approval under national law and applicable institutional regulations.

Consent to participate

All carriers underwent DNA-based screening and standard operations for MEN2A-associated tumors after informed consent according to applicable diagnostic and therapeutic standards (routine patient care).

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Not applicable (aggregate data only, no patient level data).

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Machens, A., Lorenz, K., Weber, F. et al. Medullary thyroid cancer and pheochromocytoma in MEN2A: are there parent of origin effects on disease expression?. Familial Cancer 21, 473–478 (2022). https://doi.org/10.1007/s10689-021-00282-w

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  • DOI: https://doi.org/10.1007/s10689-021-00282-w

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