Abstract
Lynch syndrome, or hereditary nonpolyposis colorectal cancer, is a condition of susceptibility to cancer that is caused by a germline mutation in a DNA-mismatch repair gene. Cancers develop early in the colon and rectum, endometrium, ovary, small bowel, ureter, and renal pelvis. Affected women have a 40% to 60% chance of developing endometrial cancer and a 10% to 20% lifetime risk of ovarian cancer. Some have proposed removal of the uterus and ovaries on a preventive basis despite a lack of evidence that it is beneficial. This study examined the risk of endometrial and ovarian cancer in women found in 3 registries in the years 1973–2004 with MLH1, MSH2, or MSH6 germline mutations. Sixty-one women having prophylactic hysterectomy and 47 undergoing bilateral salpingo-oophorectomy in addition were matched, respectively, with 210 and 223 mutation-positive women of similar age who did not have prophylactic surgery.None of the women having prophylactic hysterectomy developed endometrial cancer compared with 33% of control women. Operated women were followed for approximately 13 years on average and control women for 7 years. The prevented fraction, or proportion of potential new cancers prevented, was 100% with a 95% confidence interval (CI) of 90% to 100%. Three of 25 women who died during follow up had undergone prophylactic surgery. Ovarian cancer developed in 5% of control women but in none of the 47 having bilateral salpingo-oophorectomy at the time of prophylactic hysterectomy. The prevented fraction was 100%, with a 95% CI of −62% to 100%. One woman (1.6%) had surgical complications.Prophylactic surgery effectively prevents gynecologic cancers in women with Lynch syndrome. In particular, hysterectomy with bilateral salpingo-oophorectomy can prevent both endometrial and ovarian cancers in affected women. These women should have an opportunity to discuss the tradeoff between a reduced risk of cancer and the risks and side effects of surgery.