Lynch syndrome (HNPCC)

Lynch syndrome, also referred to as hereditary non-polyposis colorectal cancer (HNPCC), accounts for somewhere between 2 and 5% of all CRC. It has been shown that Lynch syndrome (LS) is a result of germline mutations in genes involved in DNA mismatch repair (MMR) MSH2, MLH1, MSH6, and PMS2, whereas as HNPCC refers to families that adhere to the Amsterdam criteria or iterations of it. More recently, it has been reported that loss of EPCAM is associated with Lynch syndrome, by virtue of it changing the epigenetic status of the promoter region of MSH2. Mutation carriers are at high risk of developing colorectal cancer (CRC), and endometrial cancer (EC) at unusually young ages. Other, extra-colonic tumor types such as ovarian, small bowel, urinary, biliary tract, gastric, and brain tumors, have also been associated with HNPCC. Over half the cancer deaths in HNPCC families are due to extra-colonic malignancies. The benefit of surveillance for gynecological cancers is not yet proven and there is no consensus on the optimal surveillance recommendations for women with MMR mutations. We performed a systematic review of the literature and evaluated cancer risk in Polish HNPCC families classified into either Lynch syndrome (LS, MMR mutations detected) or HNPCC (fulfillment of the Amsterdam or modified Amsterdam criteria). CRC detection screening strategy based upon colonoscopy has been documented to decrease CRC mortality. Published data clearly indicates no benefit for ovarian cancer screening in contrast to risk reducing surgery. Due to the high cumulative risk of CRC full colonoscopy is recommended in HNPCC families beginning from age of 20-25 yrs every one-two years. Due to the high risk of EC it is reasonable to offer, after the age of 35 years, annual clinical gynecologic examinations with transvaginal ultrasound supported by routine aspiration sampling of the endometrium for women from either LS or HNPCC families. An alternative option, which could be taken into consideration for women preferring surgical prevention, is risk reducing total hysterectomy (with bilateral salpingo-oophorectomy) for carriers after childbearing is complete. Due to the increased risk of OC and absence of any benefit from gynecological screening reported in the literature it is recommended that prophylactic oophorectomy for female carriers of MMR mutations after 35 year of age should be considered as a risk reducing option. Annual transvaginal ultrasound supported by CA125 or HE4 marker testing should be performed after prophylactic surgery in these women.