Establishment of a Mesoamerican-Caribbean south-south research platform: Challenges in the Meriva (curcuminoids) Gastric Cancer Chemoprevention Trial.

Gastric adenocarcinoma (GAC) is the fourth-leading global cause of cancer mortality and leading infection-associated cancer. High incidence regions include Latin America and Eastern Asia. Immigrants from high incidence regions maintain their GAC risk. GAC is a major U.S. cancer disparity, incidence rates are 2-10 time higher in non-white populations. Emerging guidelines recommend 3-year surveillance endoscopy for patients with high-risk gastric premalignant conditions (GPMCs). Clinical trials of GPMC chemoprevention agents are lacking. We conducted an NCI Division of Cancer Prevention-funded, phase II placebo-controlled chemoprevention trial in patients with GPMCs (atrophic gastritis, intestinal metaplasia) with a highly bioavailable preparation of curcuminoids (Meriva®). The trial sites in Puerto Rico and rural Honduras had important characteristics: (1) representative Caribbean and Mesoamerican populations, linked to large U.S. immigrant populations; (2) high prevalence of H. pylori infection and GPMCs; (3) absence of turmeric and curcuminoids in the local diets; (4) proven bidirectional collaboration with U.S. academic institutions. H. pylori-negative GPMC patients were randomized to study drug (500 mg po bid) or placebo for 180 days (NCT02782949), with primary outcomes based upon histologic parameters. Principal study challenges included: (1) international regulatory environment; (2) research infrastructure strengthening, particularly in Central America; (3) participant recruitment in Honduras wherein only 10-15% are H. pylori negative; (4) the Covid-19 pandemic; and (5) natural disasters (3 hurricanes). There were no losses to follow-up related to the pandemic or natural disasters. In conclusion, the south-south partnership provides a model for chemoprevention and translational studies in Latino populations with prevalent cancers such as GAC.

Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico.

BACKGROUND: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. METHODS: Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests. RESULTS: Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. CONCLUSIONS: The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted.

Racial/ethnic disparities in gastric cancer: A 15-year population-based analysis.

BACKGROUND AND AIMS: Disparities in gastric cancer incidence and mortality have been reported among ethnic/racial groups. While gastric cancer is not common in the U.S., it is among the top 10 causes of cancer-related death among Hispanics living in Puerto Rico (PRH). This study compared gastric cancer incidence rates during a 15-year period (2002-2006, 2007-2011, and 2012-2016) between PRH and racial/ethnic groups in the mainland U.S., including Non-Hispanic Whites (NHW), Non-Hispanics Blacks (NHB), Hispanics (USH), and Non-Hispanic Asian or Pacific Islanders (NHAPI). METHODS: Primary gastric cancer cases (ICD-O-3 codes C16.0 to C16.9) from the Puerto Rico Central Cancer Registry and SEER diagnosed from January 1, 2002 to December 31, 2016 were included in the analysis. The Joinpoint Regression Program and standardized rate ratios were used to estimate Annual Percent Changes (APC) and differences in gastric cancer incidence among racial/ethnic groups, respectively. RESULTS: Our analysis included 83,369 gastric cancer cases (PRH n = 4202; NHW n = 43,164; NHB n = 10,414; NHAPI n = 11,548; USH n = 14,041). USH had the highest number of cases among individuals <50 years, whereas NHW and PRH had the highest percentage among individuals ≥50 years. PRH and USH were the only groups with increasing APCs among individuals <50 years. CONCLUSIONS: Gastric cancer continues to be a common cancer among PRH, despite the overall decrease in incidence among other racial/ethnic groups. Studies evaluating the gastric cancer risk factors among high-risk groups are necessary to establish health policy and modify gastric cancer screening algorithms among Hispanics.

Gastric Intestinal Metaplasia: Demographic and Epidemiological Characterization in Puerto Rican Hispanics (2012-2014).

BACKGROUND AND AIMS: Gastric cancer is the 5th leading cause of cancer mortality worldwide and the leading infection-associated cancer. Helicobacter pylori is the most common chronic bacterial infection in humans and the major predisposing factor for the development of gastric intestinal metaplasia (GIM), the principal preneoplastic lesion in the gastric carcinogenesis pathway. GIM surveillance is now recommended for individuals among high-risk subgroups by three major gastroenterology societies in Europe, England, and U.S. Our objective was to provide the initial epidemiologic data for GIM among Hispanics in Puerto Rico. METHODS: Using a cross-sectional study design, we analyzed an extensive pathology database (n = 43,993) that captured approximately 50% of all endoscopy biopsies taken during 2012-2014 at academic, public, and private sectors in Puerto Rico. Prevalence estimates of GIM, GIM subgroups, and H. pylori status were estimated using logistic regression models. RESULTS: A total of 4,707 GIM cases were identified during the study period for a prevalence rate of 10.7%. H. pylori was detected in 26.9% (95% CI: 25.7-28.2) of the GIM cases. The majority of the pathology reports lacked information regarding the high-risk subtypes (99.6%) and extension (71.2%). CONCLUSIONS: The prevalence of GIM among Hispanics living in Puerto Rico may be higher than in U.S. mainland non-Hispanic populations. The prevalence of H. pylori detected in our study population was comparable to the rates reported in the mainland U.S. Standardization of the endoscopy biopsy protocol and pathology reporting is needed to characterize and risk stratify GIM surveillance programs in Puerto Rico.

Association of genetic ancestry with colorectal tumor location in Puerto Rican Latinos.

BACKGROUND: Colorectal cancer (CRC) is the first cause of cancer deaths among Puerto Ricans. The incidence and mortality of CRC in Puerto Rico continue to be on the rise. The burden of CRC in Puerto Rico is higher than among US Hispanics and is second only to African Americans, thus supporting the importance of studying this CRC health disparity. The genetic background of the Puerto Rican population is a mix of European, African, and Amerindian races, which may account, in part, for the differences observed in the CRC mortality rates among Puerto Ricans. The objective of the study was to assess the role of genetic ancestry in CRC risk and its association with clinicopathological features of CRC tumors in Puerto Ricans. RESULTS: We used a validated panel of 105 ancestry informative markers (AIMs) to estimate genetic ancestry in 406 Puerto Rican CRC cases and 425 Puerto Rican controls. We examined the association of genetic ancestry with CRC risk and tumor clinicopathological characteristics. CONCLUSIONS: The mean ancestry proportions in the study population were 61% European, 21% African, and 18% Amerindian. No association was observed between genetic ancestry and risk of CRC. However, African ancestry was associated with an increased risk of developing rectal tumors (OR = 1.55, 95% CI 1.04-2.31). Additional studies are needed to fully elucidate the role of African ancestry in CRC carcinogenesis.

The Presence of Gut Microbial Genes Encoding Bacterial Genotoxins or Pro-Inflammatory Factors in Stool Samples from Individuals with Colorectal Neoplasia.

Gut bacterial toxins are thought to contribute to the development of colorectal cancer (CRC). This study examines the presence of specific gut bacterial toxin genes in stool samples from individuals with colorectal neoplasia (adenomas and/or CRC). The presence of bacterial genes encoding genotoxic or pro-inflammatory factors (pks, tcpC, gelE, cnf-1, AMmurB, and usp) was established by PCR of stool samples from individuals from mainland US (n = 30; controls = 10, adenoma = 10, CRC = 10) and from Puerto Rico (PR) (n = 33; controls = 13; adenomas = 8; CRC = 12). Logistic regression models and multinomial logistic regression models were used to estimate the magnitude of association. Distinct bacterial gene profiles were observed in each sample cohort. In individuals with CRC, AMmurB was detected more frequently in samples from the US and gelE in samples from PR. In samples from PR, individuals with ≥2 gut bacterial toxin genes in stool had higher odds of having colorectal neoplasia (OR = 11.0, 95%: CI 1.0⁻637.1): however, no significant association between bacterial genes and colorectal neoplasia was observed in the US cohort. Further analyses are warranted in a larger cohort to validate these preliminary findings, but these encouraging results highlight the importance of developing bacterial markers as tools for CRC diagnosis or risk stratification.

Prevalence of Synchronous Oligopolyposis in Incident Colorectal Cancer: A Population-Based Study.

OBJECTIVE: Colorectal cancer (CRC) is a leading causes of cancer death among men and women. The purpose of this study was to determine the prevalence of oligopolyposis (≥20 synchronous colorectal adenomas) and its associated clinicopathological characteristics in Hispanics with incident CRC. METHODS: Pathology reports from individuals diagnosed with CRC (2007 to 2011) were obtained from the PR Central Cancer Registry. Colorectal polyp burden was calculated using pathology reports and the data was normalized to colon segment size. Comparisons of demographic and clinicopathological characteristics by synchronous oligopolyposis status (<20 vs. <= *20) were performed using the chi-square or Fisher's exact test. Multivariate logistic regression models were fitted to estimate the adjusted prevalence odds ratios (aPOR), with 95% confidence intervals (CI). All analyses were performed using Stata (v.12.0). RESULTS: Analyses of 1,573 colectomy specimens was performed. Oligopolyposis was observed in 9.47% (149 of 1,573) of the subjects with incident CRC. Increasing age (aPOR50-64 = 1.72, 95% CI: 0.59-5.02; aPOR65-74 = 1.83, 95% CI: 0.64-5.27; aPOR≥75 = 2.67, 95% CI: 0.93-7.64) and proximal CRC tumor location (POR = 2.91, 95% CI:1.98-4.30) were significantly associated with having oligopolyposis at CRC diagnosis. However, subjects diagnosed with CRC at a regional stage (aPORRegional = 0.50, 95% CI: 0.32-0.79) or distant stage (aPORDistant = 0.45, 95% CI: 0.29-0.69) were less likely to have synchronous oligopolyposis (p<0.05). CONCLUSION: Our findings suggest that genetic syndromes associated with colorectal polyposis may be implicated in a higher than expected number of CRC cases. Individuals with CRC and synchronous oligopolyposis should receive genetic counseling.

Seroprevalence of Helicobacter pylori in Hispanics living in Puerto Rico: A population-based study.

BACKGROUND: Helicobacter pylori is an important etiologic factor for peptic ulcers and gastric cancer, one of the top ten leading causes of cancer death in Puerto Rico. However, the prevalence of H. pylori infections in this population was previously unknown. The aim of this study was to examine the seroprevalence of H. pylori and its associated risk factors in Puerto Rico. MATERIALS AND METHODS: A cross-sectional study was designed using an existing population-based biorepository. Seropositivity was determined using the Premier™ H. pylori immunoassay. Helicobacter pylori seroprevalence was estimated with 95% confidence using marginal standardization following logistic regression. To assess the risk factors associated with H. pylori seropositivity, a multivariable log-binomial model was fitted to estimate the prevalence ratio (PR) and its 95% confidence interval (95% CI). RESULTS: A total of 528 population-based serum samples were analyzed. The mean age of the study population was 41 ± 12 years, of whom 55.3% were females. The overall seroprevalence of H. pylori was 33.0% (95% CI = 28.3%-38.1%). Increasing age and having <12 years of education were significantly (P < .05) associated with H. pylori seropositivity in the multivariable model; however, residing in counties with low population density reached marginal significance (P = .085). CONCLUSIONS: We report that H. pylori infection is common among Hispanics living in Puerto Rico. The H. pylori seroprevalence observed in Puerto Rico is similar to the seroprevalence reported in the overall population of the United States. The association between H. pylori seroprevalence and the risk factors analyzed offers insight into the epidemiology of gastric cancer in Puerto Rico and warrants further investigation.

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

Hereditary cancer predisposition syndromes comprise approximately 10% of diagnosed cancers; however, familial forms are believed to account for up to 30% of some cancers. In Hispanics, the most commonly diagnosed hereditary cancers include colorectal cancer syndromes such as, Lynch Syndrome, Familial Adenomatous Polyposis, and hereditary breast and ovarian cancer syndromes. Although the incidence of hereditary cancers is low, patients diagnosed with hereditary cancer syndromes are at high-risk for developing secondary cancers. Furthermore, the productivity loss that occurs after cancer diagnosis in these high-risk patients has a negative socio-economic impact. This review summarizes the genetic basis, phenotype characteristics, and the National Comprehensive Cancer Network's screening, testing, and surveillance guidelines for the leading hereditary cancer syndromes. The aim of this review is to promote a better understanding of cancer genetics and genetic testing in Hispanic patients.

Clinical Cancer Genetics Disparities among Latinos.

The three major hereditary cancer syndromes in Latinos (Hereditary Breast and Ovarian Cancer, Familial Adenomatous Polyposis and Lynch Syndrome) have been shown to exhibit geographic disparities by country of origin suggesting admixture-based disparities. A solid infrastructure of clinical genetics geared towards diagnosis and prevention could aid in reducing the mortality of these cancer syndromes in Latinos. Currently, clinical cancer genetic services in Latin America are scarce. Moreover, limited studies have investigated the mutational spectrum of these cancer syndromes in Latinos resulting in gaps in personalized medicine affecting diagnosis, treatment and prevention. The following commentary discusses available genotype and clinical information on hereditary cancer in Latinos and highlights the limited access for cancer genetic services in Latin America including barriers to genetic testing and alternatives for providing better access to genetic services. In this review, we discuss the status of clinical genetic cancer services for both US Latinos and those Latinos living in Latin America.

Current Perspectives on Gastric Cancer.

Gastric cancer (GC) is third leading cause of cancer-related death. Only 28.3% of new GC cases survive more than 5 years. Although incidence has declined in the United States, an increase is estimated for 2016. Risk factors include sex (risk is higher in men), Helicobacter pylori infection, heredity, and lifestyle. GC is usually diagnosed between the ages of 60-80 years. Prognosis of GC is largely dependent on the tumor stage at diagnosis and classification as intestinal or diffuse type; diffuse-type GC has worse prognosis. Chemoprevention has been shown to decrease risk, but is currently not used clinically.

High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case-Control Study.

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.

Colorectal Cancer Survival Disparities among Puerto Rican Hispanics: A Comparison to Racial/Ethnic Groups in the United States.

PURPOSE: Ethnic/racial disparities in colorectal cancer (CRC) survival have been well documented. However, there is limited information regarding CRC survival among Hispanic subgroups. This study reports the 5-year relative survival of Puerto Rican Hispanic (PRH) CRC patients and the relative risk of death compared to other racial/ethnic groups in the US. METHODS: CRC incidence data from subjects ≥50 years was obtained from the Puerto Rico Central Cancer Registry and the Surveillance, Epidemiology and End Results (SEER) database from January 1, 2001 to December 31, 2003. Relative survival rates were calculated using the life tables from the population of PR and SEER. A Poisson regression model was used to assess relative risk of death by stage, sex, and age. RESULTS: A total of 76,444 subjects with incident CRC were analyzed (non-Hispanic White (NHW) n=59,686; non-Hispanic black (NHB) n=7,700; US Hispanics (USH) n=5,699; PRH n=3,359). Overall and stage-specific five-year survival rates differed by race/ethnicity. When comparing PRH to the other racial/ethnic groups, PRH had the lowest survival rates in regional cancers and were the only racial/ethnic group where a marked 5-year survival advantage was observed among females (66.0%) compared to males (60.3%). A comparable and significantly higher relative risk of death of CRC was observed for PRH and NHB compared to NHW. CONCLUSIONS: Our findings establish baseline CRC survival data for PRH living in Puerto Rico. The gender and racial/ethnic disparities observed in PRH compared to US mainland racial/ethnic groups warrant further investigation of the risk factors affecting this Hispanic subgroup.

Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites.

Multidrug resistance-associated proteins (MRPs) belong to the C-family of ATP-binding cassette (ABC) transport proteins and are known to transport a variety of physiologically important compounds and to be involved in the extrusion of pharmaceuticals. Rodent malaria parasites encode a single ABC transporter subfamily C protein, whereas human parasites encode two: MRP1 and MRP2. Although associated with drug resistance, their biological function and substrates remain unknown. To elucidate the role of MRP throughout the parasite life cycle, Plasmodium berghei and Plasmodium falciparum mutants lacking MRP expression were generated. P. berghei mutants lacking expression of the single MRP as well as P. falciparum mutants lacking MRP1, MRP2 or both proteins have similar blood stage growth kinetics and drug-sensitivity profiles as wild type parasites. We show that MRP1-deficient parasites readily invade primary human hepatocytes and develop into mature liver stages. In contrast, both P. falciparum MRP2-deficient parasites and P. berghei mutants lacking MRP protein expression abort in mid to late liver stage development, failing to produce mature liver stages. The combined P. berghei and P. falciparum data are the first demonstration of a critical role of an ABC transporter during Plasmodium liver stage development.

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

Familial adenomatous polyposis (FAP) is an inherited form of colorectal cancer 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 (SIR) of TC in Hispanic FAP patients. TC incidence rates in patients with FAP between the periods of January 1, 2006 to December 31, 2013 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). The study population consisted of 51 Hispanic patients with FAP and 3239 with TC from the general population. The 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). In Hispanic patients with FAP, the 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). Hispanic FAP patients are at a high risk for TC compared to the general population. Our incidence rates 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.

Colorectal Cancer Biomarkers: Where Are We Now?

Colorectal cancer is one of the major causes of cancer-related death in the Western world. Patient survival is highly dependent on the tumor stage at the time of diagnosis. Reduced sensitivity to chemotherapy is still a major obstacle in effective treatment of advanced disease. Due to the fact that colorectal cancer is mostly asymptomatic until it progresses to advanced stages, the implementation of screening programs aimed at early detection is essential to reduce incidence and mortality rates. Current screening and diagnostic methods range from semi-invasive procedures such as colonoscopy to noninvasive stool-based tests. The combination of the absence of symptoms, the semi-invasive nature of currently used methods, and the suboptimal accuracy of fecal blood tests results in colorectal cancer diagnosis at advanced stages in a significant number of individuals. Alterations in gene expression leading to colorectal carcinogenesis are reflected in dysregulated levels of nucleic acids and proteins, which can be used for the development of novel, minimally invasive molecular biomarkers. The purpose of this review is to discuss the commercially available colorectal cancer molecular diagnostic methods as well as to highlight some of the new candidate predictive and prognostic molecular markers for tumor, stool, and blood samples.

Type 2 diabetes mellitus and colorectal neoplasia risk in Hispanics: a case-control study.

AIMS: There is inconclusive evidence regarding the potential link between diabetes mellitus (DM) and colorectal cancer (CRC). Associations between type 2 DM and colorectal neoplasia (CRN; colorectal cancer and/or adenomas) have not been well studied in Hispanics, an ethnic minority at high risk for type 2 DM. This study aims to assess the association between type 2 DM and CRN in Hispanics. METHODS: Hispanics with incident CRN and colonoscopy-negative controls from 2005 to 2009 were evaluated. Diagnosis of type 2 DM was established by previous medical diagnosis and/or use of DM treatments. Unconditional logistic regression was performed to estimate odds ratios for the association between type 2 DM and CRN. RESULTS: A total of 451 participants (mean age 61.1±11.9years, 59.6 % men) were evaluated (218 with incident CRC, 77 with colorectal adenomas, and 156 colonoscopy-negative controls). The prevalence of type 2 DM in this study was 25.1%. After adjusting for potential confounding variables, women with type 2 DM were 2.74 (95% CI: 0.94-7.99) times more likely to have CRN and 4.83 times more likely to present with proximal colonic CRN (95% CI: 1.25-18.58) than women without type 2 DM. No statistically significant associations were found between type 2 DM and CRN among men. CONCLUSIONS: An increased odds for CRN and proximal location of CRN was observed among Hispanic women with type 2 DM. Since DM is a highly prevalent disease in this population, adherence to routine CRC screening is of outmost importance.

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome.

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.

Report of a Novel Mutation in MLH1 Gene in a Hispanic Family from Puerto Rico Fulfilling Classic Amsterdam Criteria for Lynch Syndrome.

In Puerto Rico, colorectal cancer (CRC) represents the second leading cause of cancer in men and women. Familial CRC accounts for 10-15% of the total CRC cases, while Lynch syndrome accounts for approximately 2-4% of cases. Limited information is available about the prevalence, clinical manifestations, and genetic mutations of hereditary CRC in US Hispanic individuals. In this paper we report a novel mutation in the hMLH1 gene in a Puerto Rican Hispanic family with Lynch syndrome recruited through the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Our proband was identified by applying Amsterdam and Bethesda criteria for Lynch syndrome, analysis of protein expression by immunohistochemistry, and genetic sequencing of the mismatch repair genes. A novel mutation at c.2044_2045 in hMLH1 consisting of the deletion of two consecutive nucleotides (AT) at exon 18 was identified. This deletion causes a frameshift in the protein coding sequence at p.682 resulting in premature termination and a truncated MLH1 protein. To our knowledge, this mutation has not been previously reported in the literature. The detection of this novel mutation in MLH1 further emphasizes the need for genetic testing in at-risk patients for hereditary CRC from various ethnic and racial backgrounds.