Ovarian Cancer Genetics

At its most basic level, cancer is a genetic disease, resulting from a step-wise accumulation of mutations in genes that normally control cell growth. The majority of gene mutations involved in cancer are somatic, meaning that they are found only in that individual’s cancer cells. Somatic mutations may occur by chance, as a result of the aging process, or due to environmental and lifestyle exposures. In contrast, germline mutations are inherited from a parent at the time of conception and are present in every cell of the body. Only a small portion of all cancers occur in individuals who carry an inherited mutation that predisposes them to develop cancer. Germline mutations in specific tumor suppressor genes and DNA mismatch repair genes have been associated with numerous hereditary cancer syndromes.

The hereditary cancer susceptibility genes that have been identified to date are highly penetrant, meaning that mutations lead to a risk of developing cancer that is significantly above average. Since cancer is a multi-step process, the presence of a germline mutation makes a person essentially ìone step closerî to cancer from the time of birth than the average person, thereby increasing the chance of early-onset cancer and multiple primary cancers. Although a significant risk factor, a germline mutation does not guarantee that cancer will develop. The likelihood that an individual who inherits a mutation will ultimately develop cancer is dependent on other factors that influence the occurrence of subsequent mutations, such as modifier genes and poorly understood diet, lifestyle, and environmental factors.

Forms of Inherited Disease

Epidemiological studies and detailed analysis of familial EOC pedigrees suggest at least three forms of inherited disease:

  1. Hereditary, site-specific ovarian carcinoma (ovarian carcinoma without breast cancer)
  2. Breast and ovarian cancer syndrome (Lynch type I, including 1st or 2nd degree relatives)
  3. Hereditary nonpolyposis colorectal carcinoma (HNPCC, Lynch type II, ovarian cancers associated with an excess of colorectal, prostate, and endometrial carcinomas).

Only 5-10 percent of ovarian cancers are due to inherited genetic mutations. EOC most commonly occurs in a sporadic fashion without any antecedent history of familial disease. Epidemiologic factors associated with EOC include nulliparity, personal history of colon or breast cancer, affected 1st degree relatives with EOC, or a family history of a recognized inherited malignancy syndrome.

Contact Us

Mount Sinai Ovarian Cancer Risk Assessment Program
Tel: 212-241-1111