Su1946 Clinical Characterization and Mutation Spectrum in Caribbean Hispanic Families With Lynch Syndrome: Molecular and Social Disparities

Background Lynch Syndrome is an inherited form of colorectal cancer caused by germline mutations in the Mismatch Repair (MMR) genes. It accounts for approximately 5% of all colorectal cancers. The prevalence of Lynch Syndrome among US Hispanics is unknown. The objective of this studywas to describe the germlinemutation spectrum and clinicopathological associations of Lynch Syndrome in Caribbean Hispanics from Puerto Rico and Dominican Republic. Methods Subjects were recruited through the Puerto Rico Familial Colorectal Cancer Registry between January 2010 to June 2014 and were classified according to Amsterdam and Bethesda clinical guidelines. For those tumors with lack of expression of MMR protein, gene sequencing was ordered. Results 89 CRC Caribbean Hispanic patients, with suspected LS were referred to the Hereditary Cancer Clinic. Nine-teen (21.3%) patients met Amsterdam Criteria (I/II) and 70 (78.7%) met Bethesda guidelines. From the 89 patients who received genetic counseling, 31 had direct MMR germline analysis and 21 (71.0%) had a germline mutation in one of the MMR genes. The mutation spectrum of Caribbean Hispanic LS patients was composed mostly of MSH2 (66.7 %) mutations, followed by MLH1 (25.0 %). Only one mutation was identified in MSH6 (8.3 %). A previously unidentified mutation inMLH1 gene c.2044_2045del was found in one Caribbean Hispanic family. MMR mutationpositive individuals were more likely to have a prominent family history of CRC and tumors located at the proximal colon compared to MMR mutation-negative CRC patients. Compared to MSH2 mutation carriers, MLH1 mutation-positive individuals were more likely to have a strong family history of CRC, earlier age at diagnosis and LS-associated cancers. Insurance coverage for genetic testing was found to be limited in the study population with most patients (66%) of the individuals been denied coverage. Conclusions This report presents the first description of the mutation spectrum and clinicopathologic characteristics of LS Caribbean Hispanics patients. Our results show that the mutation spectrum of Caribbean Hispanic LS patients was composed mostly of MSH2 mutations, followed by MLH1. Due to genetic ancestry background differences among Caribbean Hispanics, compared to other Hispanics groups, there is potential for identifying novel MMR mutations associated with LS and Variables of unknown significance (VUS). Future studies should be directed towards understanding the differences in the mutation spectrum of Hispanic LS patients and implementation of widespread clinical guidelines for LS screening according to the National Comprehensive Cancer Network.