Clinical characterization and mutation spectrum in Hispanic families with adenomatous polyposis syndromes

Abstract

Background Several genetically defined hereditary CRC syndromes are associated with colonic polyposis including familial adenomatous polyposis (FAP) and MUTYH adenomatous polyposis (MAP). Limited data exists on the clinical characterization and genotypic spectrum of polyposis syndromes among Hispanics. Purpose To describe the phenotype and genotype of Puerto Rican Hispanic patients with FAP and MUTYH and compare with other ethnic and racial groups. Methods Probands were identified from the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Recruited individuals completed risk factors, medical, and family history questionnaires and underwent genetic testing for genotype analysis. Frequency analysis, chi-square, Fisher’s exact test and Wilcoxon rank-sum test were used for statistical analysis methods. Results A total of 31 FAP (from 19 families) and 13 MAP (from 13 families) Hispanic patients recruited from the Puerto Rico Familiar Colorectal Cancer Registry were evaluated. Among the FAP cases, mean age at diagnosis was 27.6 (range 9–71 years); 67.7% cases had more than 100 polyps and 41.9% had upper gastrointestinal polyps. Among the 19 FAP families, there were 77 affected FAP individuals and 26 colorectal cancer cases. Genetic mutations were available for 42.2% of FAP families; all mutations identified were unique. Surgeries were reported in 31 cases; 14 (45.2%) prophylactic surgeries and 6 (19.4%) therapeutic surgeries for management of CRC. Among MAP cases, mean age at diagnosis was 53 (range 34–76 years) and genetic analysis revealed homozygous biallelic mutations (G382D) in 53.8%, compound heterozygous mutations (G382/Y165C) in 23%, and non-G382/Y165C monoallelic mutations in 23%. Conclusions Familial cancer registries should be promoted as vehicles for detection, education and follow up of families at-risk of acquiring familial cancers. PURIFICAR is the first and only familial cancer registry in Puerto Rico providing these services to families affected with familial cancer syndromes promoting education, testing and surveillance of at-risk family members, and focusing on cancer prevention efforts. The fact that only 40% of FAP patients had access to genetic testing stresses the need to promote the establishment of policies supporting genetic testing coverage by medical insurance companies in order to provide patients with the highest standard of care to prevent cancer. Furthermore, our results suggest that Hispanics may have uncommon mutations in adenomatous polyposis related genes, which emphasize the need for full gene sequencing to establish genetic diagnosis.

Risk of thyroid cancer among Caribbean Hispanic patients with familial adenomatous polyposis

“…This investigation supports the new ACG Guidelines for FAP, which recommend annual thyroid ultrasounds [32]. In PR, mutation analysis of the APC gene is costly and not covered by most health insurance companies unless the patients have been diagnosed with CRC [18]. Diagnosis of familial polyposis syndromes is mainly based on clinical phenotype [18].…”

“…This registry contains information on the proband’s medical history, environmental exposures and family cancer history. Participants are referred to the UPR Cancer Genetics Clinic where they are offered a range of services including genetic counseling, genetic testing, and endoscopies (diagnostic and surveillance) [18] . Individuals with TC were obtained from the state- and CDC-funded Puerto Rico Central Cancer Registry (PRCCR).…”

“…In PR, mutation analysis of the APC gene is costly and not covered by most health insurance companies unless the patients have been diagnosed with CRC [18]. Diagnosis of familial polyposis syndromes is mainly based on clinical phenotype [18]. However, when a germline APC mutation is identified in an individual, other family members can be tested using single site mutation analysis, which proposes a more affordable alternative [18].…”

“…Diagnosis of familial polyposis syndromes is mainly based on clinical phenotype [18]. However, when a germline APC mutation is identified in an individual, other family members can be tested using single site mutation analysis, which proposes a more affordable alternative [18]. Such analysis identifies at-risk family members that may benefit from adequate surveillance strategies.…”

Hereditary cancer syndromes in Latino populations: genetic characterization and surveillance guidelines

“…The FAP mutation spectrum has been studied in a limited number of Hispanic countries, including Brazil [49], Argentina [50], Peru [51], Mexico [44], Puerto Rico [52], Portugal, and Spain [53] (Table 2). Most mutations identified in Hispanic patients from both Latin America, Portugal, and Spain have been in exon 15 of the APC gene (Table 2).…”