The evolution of colorectal cancer genetics—Part 2: clinical implications and applications Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Thursday, November 13, 2014

The evolution of colorectal cancer genetics—Part 2: clinical implications and applications



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The risk of CRC in LS is approximately 60-85% depending on which MMR gene is involved. Patients with MLH1 and MSH2 mutations have a higher risk of cancer, with diagnosis at a younger age, compared to MSH6 and PMS2 mutations (25,26). MLH1 mutation carriers have a higher risk of CRC, while MSH2 carriers have a higher rate of multiple primary extracolonic cancers, to include brain (glioblastoma), ovarian, stomach, hepatobiliary, urinary tract, breast, and prostate cancers (27-32). Colonoscopy screening decreases the risk of a second CRC by 62% when patients have routine surveillance (33). It is rare for colonoscopy to miss a polyp >10 mm. However, for polyps between 1-5 mm, up to 35% can be overlooked (34). With this knowledge, prophylactic colectomy may be ideal for some patients, requiring only a subsequent yearly rectal surveillance. Prophylactic colectomy before the age of 25 has been associated with the greatest increase in life expectancy when compared to older patients and those where surgery was performed after a CRC diagnosis (35). It is still widely debated about recommendations for a prophylactic colectomy. It is important to evaluate the patient for both emotional and physical perspectives, understand his or her MMR mutation status, and ensure that a genetic counselor is actively engaged with the decision making process. In women who present with uterine cancer, prophylactic colectomy can be considered in addition to the surgical treatment of gynecologic diseases, if the patient is being managed in a comprehensive manner (36). Prophylactic hysterectomy and bilateral salpingo-oophorectomy is a prudent option given limited endometrial and extremely poor ovarian cancer screening (36).......

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