Ovarian cancer may be paternally inherited

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The disease allele may be passed from affected grandmother to granddaughter through the father’s inherited genes.
The disease allele may be passed from affected grandmother to granddaughter through the father’s inherited genes.

Ovarian cancer risk is elevated in women with sisters or paternal grandmothers who have been affected, according to a study published in PLoS Genetics.

Kevin H Eng, PhD, of the Department of Biostatistics and Bioinformatics at Roswell Park Cancer Institute in Buffalo, NY, and colleagues hypothesized that ovarian cancer may be X-linked and the associated genes may be passed from the paternal grandmother though the father's inherited genetic material.

The investigators conducted a series of tests using DNA from 186 women with ovarian cancer who were registered in the Familial Ovarian Cancer Registry at Roswell Park Cancer Institute via germline X-chromosome sequencing.

They reported an earlier age-of-onset in paternal grandmothers compared with maternal grandmothers (hazard ratio [HR], 1.59), though both were mutually exclusive from BRCA1 and BRCA2.

To confirm X-linked association, the researchers measured the correlation between prostate cancer in men and ovarian cancer in their mothers and daughters (odds ratio [OR], 2.34). Mothers who did not have ovarian cancer but had affected daughters had significantly more female than male offspring (OR, 1.96).

“We have presented evidence that there may exist an X-linked model of transmission of an ovarian cancer susceptibility gene,” the authors wrote.

“Future studies are warranted to confirm the identity and function of the X-linked gene that contributes to familiar transmission of ovarian cancer.”

Reference

  1. Eng KH, Szender JB, Etter JL, et al. Paternal lineage early onset hereditary ovarian cancers: A familial ovarian cancer registry study. PLoS Genetics. 2018 Feb 15. doi:10.1371/journal.pgen.1007194
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