title: Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome.
abstract: Lynch syndrome (LS) is an inherited form of colorectal cancer (CRC) caused by germline mutations in the mismatch repair (MMR) genes. It accounts for approximately 5% of all CRCs. The prevalence of LS among US Hispanics is unknown. The objective of this study was to describe the germline mutations of LS in Caribbean Hispanics from Puerto Rico and Dominican Republic. A total of 89 subjects were recruited through the Puerto Rico Familial Colorectal Cancer Registry and were classified according to Amsterdam and Bethesda clinical guidelines. For those tumors with lack of expression of MMR protein, gene sequencing was ordered. A total of 35 individuals with deficient MMR system were identified: 22 had MMR mutations and 13 had tumors with absent MMR protein expression. Our results show that the mutation spectrum of Caribbean Hispanic LS patients was composed mostly of MSH2 (66.7%) mutations, followed by MLH1 (25.0%). One mutation was identified in MSH6 (8.3%). A previously unidentified mutation in MLH1 gene c.2044_2045del was found in one Caribbean Hispanic family. MMR mutation-positive individuals were found to be more likely to have a prominent family history of CRC and tumors located at the proximal colon. Compared to MSH2 mutation carriers, MLH1 mutation-positive individuals were more likely to have a strong family history of CRC and LS associated cancers. Furthermore, insurance coverage for genetic testing was found to be limited in the study population with 65.1% of the individuals recruited were denied coverage. This report presents the first description of the mutation spectrum and clinicopathologic characteristics of LS Caribbean Hispanics patients.
authors.affiliation: Department of Gastrointestinal Oncology and Genetics, University of Puerto Rico Comprehensive Cancer Center, PMB711 Ave. De Diego 89 Ste. 105, San Juan, PR, 00927-6346, USA, marcia.cruz1@upr.edu.
authors.forename: Marcia
authors.initials: M
authors.lastname: Cruz-Correa
authors.forename: Yaritza
authors.initials: Y
authors.lastname: Diaz-Algorri
authors.forename: Julyann
authors.initials: J
authors.lastname: Pérez-Mayoral
authors.forename: Wasilah
authors.initials: W
authors.lastname: Suleiman-Suleiman
authors.forename: Maria del Mar
authors.initials: Mdel M
authors.lastname: Gonzalez-Pons
authors.forename: Carlos
authors.initials: C
authors.lastname: Bertrán
authors.forename: Nicolás
authors.initials: N
authors.lastname: Casellas
authors.forename: Natalia
authors.initials: N
authors.lastname: Rodríguez
authors.forename: Sherly
authors.initials: S
authors.lastname: Pardo
authors.forename: Keyla
authors.initials: K
authors.lastname: Rivera
authors.forename: Rafael
authors.initials: R
authors.lastname: Mosquera
authors.forename: Segundo
authors.initials: S
authors.lastname: Rodriguez-Quilichini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D017691:Caribbean Region; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000209:etiology* / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D018095:Germ-Line Mutation; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007349:Insurance, Health, Reimbursement; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D055653:Muir-Torre Syndrome / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011647:Puerto Rico
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein