Impact of colonoscopic screening in male and female Lynch syndrome carriers with an MSH2 mutation

Abstract

The lifetime risk of developing colorectal cancer (CRC) in Lynch syndrome (LS) carriers is very high. To determine the impact of colonoscopic screening in 54 male and 98 female MSH2 mutation carriers, outcomes were compared with 94 males and 76 females who were not screened. CRC incidence and survival in the screened group were compared to that expected, derived from the non-screened group. To correct for survivor bias, controls were matched for age at entry into screening and also for gender. In males, median age to CRC was 58 years, whereas expected was 47 years (p = 0.000), and median survival was 66 years vs 62 years (p = 0.034). In screened females, median age to CRC was 79 years compared to 57 years in the non-screened group (p = 0.000), and median survival was 80 years compared with expected of 63 years (p = 0.001). Twenty percent of males and 7% of females developed an interval CRC within 2 years of previous colonoscopy. Although colonoscopic screening was associated with decreased CRC risk and better survival, CRCs continued to occur. CRC development may be further reduced by decreasing the screening interval to 1 year and improving quality of colonoscopy.

Feasibility of Segmental Colectomy Followed by Endoscopic Surveillance as a Treatment Strategy for Colorectal Cancer Patients with Lynch Syndrome

“…In the present study, CRC dwell time in patients with Lynch syndrome after SGC was 22.2 months (Table 3), similar to previous reports. Moreover, these previous reports also demonstrated that the incidence of metachronous CRC within 1.5 years ranged from 17.1 to 45.5% [27, 29, 32], and that of the present study was 37.5%. When taken together, annual endoscopic surveillance should be recommended to prevent metachronous CRC and secondary surgery for metachronous CRC.…”

“…The adenoma carcinoma sequence also applies to carcinogenesis in Lynch syndrome patients, and cancer dwell time is usually shorter in patients with Lynch syndrome than in patients with sporadic CRC [28]. Previous reports demonstrated that the mean dwell time of CRC in Lynch syndrome patients ranged from 23.3 to 35.2 months [27, 29-32]. These reports were based on screening data for the initial development of CRC, and there were no studies that evaluated the endoscopic surveillance interval in Lynch syndrome patients after resection for CRC.…”

How does genetic risk information for Lynch syndrome translate to risk management behaviours?

“…Routine screening in the form of annual or biennial colonoscopy from age 25 (or 5 years earlier than the youngest CRC diagnosis in the family) is the standard recommendation for individuals with LS in Australia [6, 7]. Regular colonoscopy screening has been shown to reduce the risk of developing CRC [8] and delay the age of onset by more than 10 years [9], with CRC mortality rates reduced by up to 65% among LS individuals [7]. Colorectal surgical intervention is generally not recommended to individuals with LS until an index CRC develops.…”

Hereditary Colorectal Cancer Registries in Canada: Report from the Colorectal Cancer Association of Canada Consensus Meeting; Montreal, Quebec; October 28, 2011

“…The risk for crc in people with a strong family history is significantly reduced with appropriate cancer screening 14,15 . Well-established evidencebased recommendations are available for crc screening and surgery for individuals with ls and fap 5,6 , and screening guidelines have been developed for map 16 .…”

“…Although barriers to consistent, long-term surveillance for these high-risk carriers of germline mutations remain, centralized cancer registries have reported impressive rates of screening compliance, with noncompliance rates of less than 5% [26][27][28] . As a result, registries have demonstrated a decline in the incidence of crc; improved survival for relatives who are identified to be mutation carriers and who subsequently enrol in appropriate screening; and for newly diagnosed relatives, a life expectancy comparable to that in a general population 15,[28][29][30] . Equally important is the identification of non-carrier relatives who might be undergoing augmented screening unnecessarily.…”