Possible Hereditary Link Between Ovarian and Testicular Cancers Observed

A registry study suggests that there may be a familial association between ovarian and testicular cancers. In the study, men with testicular cancer were more likely to have a mother with ovarian cancer compared with men with other malignancies.

Testicular germ cell tumors (TGCT) are the most common malignancies among American men aged 15 to 44 years; family history of TGCT has been well established as a risk factor for these tumors. “Although familial TGCT studies have yet to characterize TGCT syndromic patterns, a biologically plausible link between TGCT and ovarian germ cell tumors has been posited,” wrote study authors led by Kirsten B. Moysich, PhD, of the Roswell Park Comprehensive Cancer Center in Buffalo.

The investigators conducted a study using data from the Familial Ovarian Cancer Registry to test for associations between ovarian cancer and TGCT. They included a total of 2,636 families with multiple cases of ovarian cancer. Results were published in Cancer Epidemiology.

The cohort contained 34 men with testicular cancer, and 2,894 men with non-testicular cancers. Of those 34 men, 24 had mothers with known ovarian cancer status, and 10 mothers (41.67%) had ovarian cancer while 14 did not. This meant that the men with testicular cancer were significantly more likely to have a mother with ovarian cancer compared with the men with other malignancies, with an odds ratio (OR) of 3.32 (95% CI, 1.46–7.55; P = .004). The same was true for having a sister with ovarian cancer, though this did not reach significance, with an OR of 1.66 (95% CI, 0.87–3.15; P = .124); of the 43 sisters of men with testicular cancer with known ovarian cancer status, 14 (32.56%) had ovarian cancer.

The men in the registry with testicular cancer fathered 13 daughters, but these daughters were either too young to be at risk for ovarian cancer, or lacked adequate follow-up. Four of 16 maternal grandmothers had ovarian cancer (25%), and none of 9 paternal grandmothers with known status had the malignancy.

The mechanism for this connection may involve X-chromosome–linked susceptibility genes, the authors wrote. “While the observed absence of ovarian cancer in paternal grandmothers of men with testicular cancer is consistent with X-linked transmission, analyses were limited by small sample sizes and X-linkage could not be conclusively established,” they noted.

An attempt to update the registry and improve the family histories and collection of biospecimens is underway, specifically in families with multiple cases of ovarian cancer as well as at least one case of testicular cancer. “These analyses may provide insight into the etiology of transmission patterns of both cancers and expose novel gene targets for prevention and therapy,” the authors wrote.