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Sustained ovulation-associated inflammatory signaling in fallopian tube epithelium as a predisposing factor of serous carcinoma

Theodore Brown

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Canadian Institutes of Health Research (CIHR)
Epithelial ovarian cancer is the fifth leading cause of cancer-related death in Canadian women and is the most lethal cancer of the female reproductive tract. Unfortunately, there are no reliable tests for early detection of the disease, and symptoms that might alert a woman to seek medical treatment at an early disease stage are easily dismissed as being due to minor ailments. A major barrier in developing tests for early detection is our lack of knowledge of how this cancer develops. Women with a family history of breast or ovarian cancer are at very high risk of developing ovarian cancer, with much of this risk being due to a mutation within the breast cancer susceptibility gene 1, referred to as BRCA1. Promising recent studies indicate that the most common and lethal form of ovarian cancer may actually arise from cells lining the fallopian tube. The fallopian tube is a structure that carries the egg cell to the uterus following its release from the ovary. Each woman has two fallopian tubes, one for each of the two ovaries. We have identified molecular differences in the fallopian tubes from women with BRCA1 mutations relative to fallopian tubes from control patients that could contribute to cancer development. Of particular interest, these differences appear only during the period of the menstrual cycle following the release of the egg cell from the ovary (ovulation), suggesting that factors associated with ovulation may contribute to predisposition to ovarian/fallopian tube cancer development. During a typical menstrual cycle, an egg cell is released from only one of the ovaries, and thus these changes may occur in the fallopian tube near the ovulating ovary and not the fallopian tube on the other side. Our studies are determining if this is indeed the case, and are identifying potential molecules that are likely to participate in turning cells within the fallopian tube to cancer cells.

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