Early-onset hereditary ovarian cancer may be an X-linked model


Previous studies have shown that for some women with ovarian cancer, their sisters also have a higher risk of developing cancer than their mothers. The cancers also developes at an earlier age-of-onset. Researchers ascertained that in 3499 grandmother-granddaughter pairs, the ratio of developing ovarian cancer in the grandmother-granddaughter pairs is higher in the paternal pairs. Researchers hypothesized that this kind of hereditary ovarian cancer may be X-linked, where the gene mutation is located on X chromosome and inherited from grandmother to father, then to granddaughter. After analyzing 892 grandmother-granddaughter pairs of familial ovarian cancer, including 157 affected granddaughters with ovarian cancer. They found the occurrence of cancer was 28.4% in paternal grandmother-granddaughter pairs and 13.9% in maternal pairs. This result is consistent with the X-linked dominant model tested by a Chi-square test. Moreover, early onset affected granddaughters coincided with the affected paternal grandmothers. In order to identify the genetic factors in these familial cases, researchers performed X chromosome exome sequencing. They identified one missense mutation (rs176026) in MAGEC3 highly associated with the paternal familial ovarian cancer cases. The result suggested there might be a paternal inherited ovarian cancer associated gene located near this locus. From pedigree analysis, male members in these families have an increased risk of prostate cancer and other cancers.

Source: Eng KH, Szender JB, Etter JL, et al. PLoS Genet. 2018, 15;14(2):e1007194

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