Lynch Syndrome diagnosis in Ireland: The impact of universal mismatch repair protein testing.

532 Background: It is estimated that approximately 2-4% of colorectal cancers (CRCs) are attributable to Lynch Syndrome (LS). Immunohistochemical testing for mismatch repair proteins is increasingly being performed on CRC specimens. In some centres all incident cases undergo this testing. An abnormal result should initiate a cascade of testing to determine if the loss of mismatch repair protein expression is sporadic or hereditary. We examined the pattern of cancer genetics referral for hereditary CRC diagnosed in Ireland under the age of 70 years. Methods: The number of patients with CRC diagnosed under the age of 70 between 2005 and 2013 was obtained from the National Cancer Registry of Ireland. The number of patients referred for cancer genetics work-up with a diagnosis of CRC < 70 years of age was ascertained from the Department of Clinical Genetics, Our Lady’s Hospital, Crumlin (DCG), the only genetics laboratory in Ireland which processes such samples. The database of the DCG was searched for referrals for hereditary CRC syndromes; and the clinical reason for referral recorded. Results: Between 2005 and 2013, 10,334 patients were diagnosed with CRC less than 70 years of age. 85% were between 50 and 69 years of age (n = 8,736). 229 people under the age of 70 years were referred for cancer genetics work-up for LS with a diagnosis of CRC. Those referred for a non-CRC LS phenotypic manifestation and for predictive testing were excluded. For 41 individuals the reason for referral was not specified. Individuals with CRC were referred for one of the following reasons: diagnosis of CRC < 70 years in 76 patients (33%), diagnosis of CRC < 70 with a family history of LS-associated malignancy in 137 patients (60%), and diagnosis of CRC < 70 with known familial genetic mutation in 16 patients (7%).This represents a referral rate of approximately 0.02% for CRC diagnosed under 70 years of age. Conclusions: 0.2% of colorectal cancer cases diagnosed at < 70 years of age in Ireland over a nine year period were referred for cancer genetics opinion. Increased immunohistochemical testing for mismatch repair proteins should result in increased cancer genetics referral, which will require appropriate service provision within oncology management pathways.