The role of Human Papillomavirus (HPV) in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC). In this case-control study, the prevalence of HPV infection in CRC (cases n = 45) and normal colon mucosa from cancer-free subjects (controls n = 36) was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2%) CRC cases (mean age 61.1 ± 10.7 years, 24 males) and in 1 of 36 (2.8%) controls (mean age 60.9 ± 9.6 years, 24 males) with an OR = 25.58 (95% CI 3.21 to 203.49). HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted.

Lynch Syndrome (LS) 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 study was to describe the germline mutations of Lynch Syndrome 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.

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.

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Background & Aims Familial adenomatous polyposis (FAP) is an inherited form of colorectal cancer (CRC) characterized by hundreds of adenomatous polyps in the colon and rectum. FAP is also associated with thyroid cancer (TC), but the lifetime risk is still unclear. This study reports the standardized incidence ratio of TC in Hispanic FAP patients. Methods TC incidence rates in patients with FAP were compared with the general population through direct database linkage from the Puerto Rico Central Cancer Registry (PRCCR) and the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR) between the periods of January 1, 2006 to December 31, 2013. The study population consisted of 51 Hispanic patients with FAP and 3,239 with TC from the general population. The Standardized incidence ratio (SIR) was calculated using the Indirect Method, defined as observed TC incidence among patients with FAP in PURIFICAR’s cohort (2006–2013) divided by the expected TC incidence based on the PR population rates (2006–2010). SIR values were estimated by sex (male, female and overall). This study received IRB approval (protocol # A2210207). Results In Hispanic patients with FAP the standardized incidence ratio (SIR) (95% CI) for TC was 251.73 (51.91 – 735.65), with higher risk for females 461.18 (55.85–1665.94) than males 131.91 (3.34–734.95). Conclusions Hispanic FAP patients are at a high risk for TC compared to the general population. Our incidence rates (SIR) are higher than previous studies, suggesting that this community may be at a higher risk for TC than previously assumed. Implementation of clinical surveillance guidelines and regular ultrasound neck screening in Hispanic FAP patients is recommended.