Prophylactic Surgery

BRCA 1 and BRCA 2 are genes that encode for proteins that help prevent breast and ovarian cancers.

Family histories of breast/ovarian cancers

Breast cancer is the second most commonly diagnosed cancer among women and the second leading cause ofcancer death in women. An estimated 217,400 new breast cancer cases were diagnosed in the United States in 2004 and about 40,600 women died of breast cancer. About 5-10% of women with breast cancer have an inherited susceptibility. After gender and age, a family history of breast or ovarian cancer is the single best predictor of the likelihood that a woman will develop these cancers (Kauff, 1609-15).

Family histories that suggest a hereditary predisposition for breast and ovarian cancer include:

multiple affected family members, particularly a mother, sister, or daughter

cancers occurring 5-15 years earlier than sporadic cancers (those not associated with a genetic risk)

two or more primary cancers in a single individual, such as breast and ovarian cancers or bilateral breast cancer (separate cancers in each breast)

male breast cancer

other multiple cancers in the family, especially prostate cancer

an Ashkenazi (eastern and central European) Jewish background.

BRCA gene alterations

BRCA stands for BReast CAncer or breast cancer susceptibility. After a long search for changes in DNA sequences that were common in breast-cancer-prone families, particularly Ashkenazi Jews, BRCA 1 was discovered in 1994 and BRCA 2 in 1995. Inherited alterations (mutations) in the DNA sequences of these genes account for 5-10% of all breast cancers.

BRCAs are inherited as autosomal dominant genes. This means that an altered BRCA gene can be passed from either a mother or a father to a son or a daughter. Humans have 23 pairs of chromosomes that carry genes. One member of each chromosome pair is inherited from the father and the other member of the pair is inherited from the mother, so that a person has two copies of each gene. If either parent has an altered BRCA, their children each have a 50% chance of inheriting the altered BRCA. Because the altered BRCA is dominant over the normal gene inherited from the other parent, a child who inherits one altered BRCA is at an increased risk for breast and/or ovariancancer. Males with an altered BRCA gene, especially BRCA 2, are at increased risk for breast and prostate cancers (King, 2251-6).

Excepting Ashkenazi Jews, the likelihood of a BRCA mutation is:

0.5% in the general population

2% in women with breast cancer

9% in women under 40 with breast cancer

5% in men with breast cancer

10% in women with ovarian cancer.

The likelihood of a BRCA mutation in Ashkenazi Jews is:

2.5% in the general population

10% in women with breast cancer

30-35% in women under 40 with breast cancer

19% in men with breast cancer

36-41% in women with ovarian or primary peritoneal or pelvic cancers (Rebbeck, 1616-22).

Among Ashkenazi Jews, 1% have an alteration called 185delAG in BRCA 1; 0.1% have a mutation called 5382insC in BRCA 1; and 1.4% have a mutation called 6174delT in BRCA 2. Each of these three mutations carries a similarbreast cancer risk. Various other ethnic groups, including Norwegians, Dutch, and Icelanders, have different specific BRCA mutations.

Although more than 2,000 mutations and DNA sequence variations have been found in BRCAs, most of them do not increase an individual's risk of developing cancer. However 0.1%-0.6% of the general population may carry a potentially damaging BRCA 1 mutation.

Not everyone with an altered BRCA gene will develop cancer. An altered BRCA increases a woman's risk ...