An Ashkenazi Jewish woman in her 50s, Rachel, is diagnosed with breast cancer. Her mother, Sadie, age 80, has a history of melanoma, which was treated successfully. Sadie's younger sister, Zelda, died of breast cancer in her early 40s many years ago. Zelda had two daughters who live far away, with whom they have lost contact. Rachel's father and his family have no history of cancer.
An astute clinician recommends genetic counseling for Rachel and Sadie to estimate their risk of carrying the hereditary ovarian and breast cancer gene mutations for BRCA1 and BRCA2. While Sadie has no interest in being tested, Rachel is found to have the harmful BRCA2 gene change. She informs her immediate family, her parents and her two brothers, of this finding. Her brothers, who have daughters in their 20s, are entirely disinterested, having no knowledge of the ramifications of this information and no personal history of cancer.
Rachel finds her long-lost cousins, Zelda's daughters, who are in their 40s with no history of cancer. She urges them to get genetic counseling, as there is a high probability that their mother had a BRCA gene mutation.
After soul searching and multiple medical and psychological consultations, Rachel undergoes double mastectomies, a hysterectomy and removal of both tubes and ovaries.
While recovering from surgery and starting chemotherapy for her breast cancer, she summons the strength to explain to her brother's daughters, her nieces, their risk of carrying a BRCA gene mutation. Meanwhile her cousins, Zelda's daughters, have happily reentered her life, grateful for the family genetic information. One cousin is positive for the BRCA gene mutation as well, and opts for the same prophylactic surgery as Rachel.
Eventually, with pressure from a doctor friend and Rachel's nieces, her brothers undergo genetic counseling and gene testing. One is positive for the BRCA2 gene mutation and one is negative. This is consistent with the 50% chance that any child can inherit a BRCA gene mutation from a parent who carries it.
These gene mutations have a dominant expression. Rachel's nieces are able to make health choices based on this information. They start hormonal contraceptives, which lower the incidence of ovarian cancer for all women by 50% when taken for just four years. The niece whose father is BRCA2 positive plans to undergo genetic counseling and gene testing at age 25. The niece whose father is BRCA2 negative is grateful for the knowledge that she need not worry about being a BRCA gene mutation carrier.
Rachel's brother who has the BRCA2 gene mutation learns that he is at greater risk for early prostate cancer, melanoma, breast cancer and other cancers. His personal physician is able to institute a vigilant screening regimen based on this knowledge.
What are BRCA1 and BRCA2 genes?
These genes are involved in cell growth control mechanisms associated with the development of hereditary breast and ovarian cancer. The name stands for breast cancer susceptibility. An inherited change in an individual's BRCA1or BRCA2 gene can be the first step toward uncontrolled tumor cell growth.
What populations are at risk to carry these genes?
BRCA alterations can be found in all ethnic populations. Groups founded by a small number of ancestors, such as Ashkenazi (Eastern European) Jews, French Canadians, Norwegians, Dutch and Icelanders may carry specific "founder" gene changes (mutations). Ashkenazi Jews have a 10-fold increase in the frequency of these genes.
What are the effects of the BRCA1 and BRCA2 gene mutations?
Breast cancer occurs in 12% of the general population compared to 50% to 87% of women with a harmful BRCA mutation.
Ovarian cancer occurs in 1.4% of the general population and 15% to 40% of women with a harmful BRCA mutation. Fallopian tube and abdominal (peritoneal) cancers, which are more frequent with BRCA gene changes, are included in this group.
Other malignancies associated with the harmful BRCA genes, which can occur in either sex, include cancers of the pancreas, stomach, gallbladder, and bile duct and melanoma.
Men with these genes changes have a large increase in breast cancer, as well as early onset prostate cancer.
Many of these cancers will develop at an earlier age than expected.
How are the BRCA gene mutations inherited?
Jeanne Homer, board-certified genetic counselor and supervisor of the Hereditary Cancer Program at Hoag Hospital in Newport Beach, explains, "There is a 50% chance that either a mother or a father carrying a harmful BRCA gene can pass it to their offspring."