BRCA1 and BRCA2 mutations can be inherited by the descendants from both the mother and the father. The chance of children inheriting these mutations is 50%.

Women with a BRCA1 mutation have a risk of ovarian cancer by age 70 years of 39% to 46% and a lifetime risk of breast cancer by age 70 years of 65% to 85%. Reported risks of ovarian and breast cancers in women by age 70 years among BRCA2 carriers are 10% to 27% and 45% to 85%, respectively.

BRCA mutation carriers are also at risk for several other cancers. Those rarer cancers reported to be associated with BRCA mutations are male breast, pancreatic, and prostate cancers, although lifetime risk of these cancers is low compared with female breast and ovarian cancer. Other malignancies, such as melanoma and biliary cancers, have also been reported to occur in BRCA carriers.

Genetic counseling and related testing are recommended for women who:

• Have been diagnosed with ovarian cancer, regardless of age
• Have been diagnosed with breast cancer at the age of 50 or earlier. In case of “triple-negative” breast cancer, the test should be done in women who developed it at the age of 60 or earlier
• Have many family members with breast or ovarian cancer, especially if diagnosed under the age of 50
• Have individual history or close relative’s history with more than one malignancy, such as bilateral breast cancer or breast and ovarian cancer
• Have a family history of cancer running over many generations. It is important to get detailed information about both the mother and father side
• Have individual or family history of malignancies other than breast and ovarian cancer (e.g., pancreatic, prostate or breast cancer in a man)

It is generally agreed that women diagnosed with a BRCA mutation should be routinely screened for cancers of which they are at risk. BRCA-carriers with intact ovaries should be offered periodic screening given their high risk for developing ovarian cancer. Screening consisting of twice-yearly CA125 and transvaginal ultrasonography beginning at age 30 to 35 years, or 5 years earlier than the earliest age of ovarian cancer in the family. 

The protective effect of oral contraceptives against ovarian cancer in high-risk women has been shown in multiple studies. BRCA carriers with intact ovaries are usually advised to use oral contraceptives to decrease their risk of ovarian cancer. However, there is conflicting evidence on the effect of oral contraceptive use on the risk of breast cancer in BRCA-positive women.

Risk-reducing surgery is the practice of removing the bilateral ovaries and fallopian tubes in BRCA carriers, and is the most efficacious method of ovarian cancer risk reduction. Risk-reducing salpingo-oophorectomy should be recommended to all BRCA carriers at the age of 40 years or after conclusion of childbearing. The fallopian tubes can also be removed at the age of 35 years, followed by removal of both ovaries at age of 40 years for women who wish to avoid early menopause.

It is is important to ensure that all ovarian and fallopian tube tissue is excised. In addition, pelvic washings should be performed at the beginning of the case because there are reports of positive cytology with no tumor found in the tissue specimen. There is currently insufficient evidence to recommend routine hysterectomy at the time of risk-reducing surgery in the absence of other uterine or cervical pathologic results.

BRCA carriers who underwent risk-reducing surgery should have subsequent surveillance owing to the risk of development of peritoneal cancer in the future (2-4%). Although the ideal follow-up protocol has not been clarified yet, clinical examination and measurement of CA-125 levels in the blood at least once a year are recommended.

The risk of developing ovarian cancer also increases in other gene mutations, such as in the PALB2, BRIP1, RAD51C, RAD51D, STK11 genes and in the Lynch syndrome.

For PALB2 carriers, the risk of breast and ovarian cancer is 44%-63% and 2%-10%, respectively. The risk of developing ovarian cancer before the age of 50 years is rather low. Therefore, the risk-reducing salpingo-oophorectomy (removal of both ovaries and fallopian tubes) is recommended at the age of 50 years.

MLH1, MSH2, MSH6, and PMS2 are all inherited in an autosomal-dominant pattern. They can be inherited by the descendants from both the mother and the father. The chance of children inheriting these mutations is 50%.   

Most patients with Lynch syndrome are found to have a mutation in either MLH1 (50%) or MSH2 (40%). Approximately 10% of cases are attributable to an MSH6 mutation. Only a few patients have a mutation in PMS2.

In women, Lynch syndrome is most commonly associated with colorectal and endometrial cancers, with a 40% to 60% lifetime risk of each. These patients typically develop endometrial cancer at an earlier age than the general population, with the mean age at diagnosis being 50 years. Approximately 10% of women diagnosed with endometrial cancer less than the age of 50 years have Lynch syndrome. The lifetime risk for developing ovarian cancer is 6% to 12%.

Multiple other malignancies are associated with Lynch syndrome, including:

• Gastric cancer
• Renal pelvis/ureteric cancer
• Small bowel cancer
• Brain cancer
• Biliary tract cancer

• Patients with synchronous or metachronous colorectal and ovarian or endometrial cancers
  
• Patients with a first-degree or second-degree relative with a known MMR mutation
• Patients with endometrial or colorectal cancer diagnosed before 50 years
  
• Patients with endometrial or ovarian cancer with synchronous or metachronous Lynch-associated malignancies
  
• Patients with colorectal or endometrial cancer and more than 2 first-degree relatives with a Lynch-associated malignancy
  
• Patient with a first-degree or second-degree relative meeting the above criteria

Women with Lynch syndrome should receive annual endometrial biopsies and transvaginal ultrasonography and biannual measurement of CA-125, once they reach the age of 30 to 35 years, or 5 years earlier than the earliest age of Lynch-related cancer in the family. 

Risk-reducing surgery including removal of the uterus (hysterectomy) and both fallopian tubes and ovaries (salpingo-oophorectomy) appears to reduce the risk of gynaecological malignancy amongst women with Lynch syndrome. Risk-reducing surgery should be offered to all women with Lynch syndrome at the age of 35 years or once childbearing is complete. Women undergoing risk-reducing surgery may still be at risk for primary peritoneal cancer (2% to 4%), and should be counseled accordingly.

Women with Lynch syndrome who who underwent risk-reducing surgery should have subsequent surveillance owing to the risk of development of peritoneal cancer in the future (2-4%). Although the ideal follow-up protocol has not been clarified yet, clinical examination and measurement of CA-125 levels in the blood at least once a year are recommended.