Jennifer Couzin-Frankel at Science writes that recent studies indicating that women of Ashkenazi descent may have cancer-related gene mutations and high rates of breast and ovarian cancer even in the absence of family history of the disease prompted her to seek genetic testing. Neither side of her family has a history of breast or ovarian cancer, she notes, but a few relatives on her father's side had had prostate cancer.
As she recounts in Science, Couzin-Frankel spoke with a genetic counselor to go through her family history and determine for what genes of a 21-gene panel she should be tested. The counselor, she says, suggests that in addition to being tested for BRCA1 and BRCA2, that Couzin-Frankel also be tested for CHEK2 mutations because her grandfather, in addition to having prostate cancer, had had colon cancer. A CHEK2 mutation, she notes, could increase her risk of breast cancer to 20 percent.
Then there's deciding what results to receive — in addition to uncovering benign and pathogenic variants, the test could find variants of unknown significance.
And that is what her results found. She has no pathogenic variants in the genes tested, but a VUS in CHEK2. Her 15 basepair deletion has been found in two men with prostate cancer and in vitro studies suggests it leads to a partial loss of function. She writes that she recalls thinking: "That's it? That's what's being shared with patients these days?"
"People need to become more comfortable with uncertainty," Baylor College of Medicine's Sharon Plon, later tells her, adding that uncertainty "does not mean that we don't know anything."