Paternal ovarian cancer
Daughters inherited a predisposition to ovarian cancer from their fathers
Daria Spasskaya, N+1
Researchers have discovered a new genetic factor that increases the risk of early ovarian cancer and is associated with the X chromosome. Presumably, this is a polymorphism in the MAGEC3 gene. As the authors explain in an article in PLoS Genetics, inheritance via the X chromosome means that women are twice as likely to receive this variant from their father than from their mother (Eng et al., Paternal lineage early onset hereditary Ovarian cancers: A Familial Ovarian Cancer Registry study).
The incidence of ovarian cancer in the world is 5-10 cases per 100 thousand women, and ten percent of these cases are determined by hereditary predisposition. Geneticists have noticed that the development of this type of cancer in a woman is often associated with an increased risk of the disease in her sister, and not in her mother. This could mean that there is a hidden hereditary factor that is passed on to daughters from fathers, and in reality some cases of spontaneous cancer development are actually hereditary.
This is possible if the desired factor (the "harmful" allele) is dominant and linked to the X chromosome - in this case, the chances of getting a mutation on the paternal side are twice as high as on the maternal side (since women have two X chromosomes, and men have one, and it is transmitted to the daughter anyway). In this case, the probability of developing ovarian cancer should be higher in the grandmother of the sick woman on the paternal side.
The scheme of transmission of the "harmful" allele from grandmother to granddaughter through her father according to the model of X-linked dominance. Female genotype – XX, male – XY (from an article in PLOS Genetics).
To test this hypothesis, the staff of the Roswell Park Cancer Research Institute in New York State turned to the records in the Family Ovarian Cancer Registry database, which has been maintained since 1981 and contains records of 5,600 cancer cases in 2,600 families. The researchers collected information about three and a half thousand pairs of "grandmother-granddaughter" and really found that the probability of developing cancer in a granddaughter is twice as high if her paternal grandmother also had ovarian cancer than if her maternal grandmother had cancer. Thus, the X-linked dominance model for hereditary ovarian cancer has been fully confirmed.
To find the genetic locus responsible for risk inheritance, scientists sequenced the X chromosomes of 159 women from this list who did not have harmful mutations in the BRCA genes. The single nucleotide polymorphism rs176026 in the coding part of the MAGEC3 gene turned out to be the most likely candidate.
Normally, this gene is expressed mainly in the testes, but its activity is also associated with tumors of various origins. In agreement with this hypothesis, the researchers found that a woman's risk of developing ovarian cancer is accompanied by an increased risk of developing prostate cancer in her father.
The main contribution to the genetic risk of ovarian cancer is made by mutations in the BRCA1 and BRCA2 genes, which are also responsible for the development of breast cancer. Mutations in BRCA1 and BRCA2 increase the risk of ovarian cancer by 10-45 percent.
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