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.

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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).

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“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.”


  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