Now in terms of etiology, there are three groups of factors that need to be taken into consideration; reproductive factors, genetic factors and environmental factors. Now the reproductive factors are shown here. There are specific associations that tend to reduce the risk, or at least are associated with a reduced risk; multiple parity, a history of breast feeding and oral contraceptive use. On the other hand, ovulation inducing drugs increase the risk for ovarian carcinoma and these facts have led to a postulation that ovarian carcinoma is related to incessant ovulation. The more you ovulate the more likely you are to develop ovarian carcinoma. For that reason, many have speculated that the rupture and then the subsequent repair of the coelomic epithelial layer overlying the ovary accounts for the chance to mutate and develop into ovarian carcinoma. Now actually this theory has not been held to quite as tightly as it was ten years ago, because everything that will reduce ovulation also reduces the motility of the fallopian tube and reduces the likelihood that external agents can be conducted into the peritoneal cavity. There are also some other factors that reduce the likelihood of external agents being conducted into the peritoneal cavity, and it seems that the more likely explanation is that all of these factors reduce the likelihood of exposure of the ovary to external agents that might participate in the carcinogenic process.

Genetic factors are listed here. Most of these are associated with a positive family history. These are the risks that we see; general population is at a 1:60 risk for developing ovarian carcinoma. That’s 1.6%. If your patient has one family member who has had ovarian carcinoma, the approximate risk is 4-5% for developing ovarian carcinoma at some point during lifetime. If that one family member is a first order relative the risk is slightly higher than this. If the one family member is less than a first order relative, the risk is slightly lower. But any family history is associated with an elevated risk. If two or more family members have ovarian carcinoma, the risk approximates 7%. Now of all ovarian carcinomas 7% of those cases will be associated with a positive family history. And among those with a positive family history, between 1-5% will have some form of identifiable familial syndrome. Most of the familial syndromes are autosomal dominant in inheritance pattern, at least we think so. Therefore the predicted risk for the offspring of someone who carries an abnormal gene would be a 50% risk. The most common of these is the breast/ovarian cancer syndrome. The breast/ovarian cancer syndrome is associated with the BRCA1 gene located on chromosome 17, region Q21. Again, this is an autosomal inheritance pattern. The penetrance appears to be about 44% by age 70. We should emphasize, but I’m sure about everybody in this audience already knows, that there can be multiple mutations of BRCA1 gene, not all of which are associated with increased risk. So you really need a family member who has the gene and also has the disease to say that that particular mutation is associated with an increased risk.

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The other two types of hereditary syndromes that have been identified to date are the ovarian cancer syndrome, which is an autosomal dominant inheritance pattern. The exact gene is still in dispute. And the Lynch type II syndrome which also is autosomal dominant in inheritance pattern, and is associated with colorectal, endometrial and breast carcinomas in addition to ovarian carcinomas.