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.
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.
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.
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.
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.
During our entire history, Puerto Rico has suffered from being in the path of Hurricanes. The implications of these events during the conduction of clinical trials present a great challenge. On ...September 20, 2017 Puerto Rico suffered its most devastating hurricane in decades. We identified four main challenges faced as a result of the natural disaster: infrastructure damage, shortage of basic necessities, transportation difficulties and communication failure. By assessing the needs of each participant, we were able to aid with food, water and medicine. Protocols were resumed shortly after the disaster, participants were located and transportation to the research center was arranged for participants. Development of emergency plans within research protocols, allocation of emergency budgets, including transportation and communication costs, may overcome some of the challenges created by a natural disaster.
Objective
Colorectal cancer is the leading cause of cancer death in Puerto Rico and third among Hispanics in the USA. Up to 2–4% of colorectal cancer cases are a result of Lynch syndrome (LS), a ...hereditary cancer syndrome caused by a germline mutation in at least one of the DNA mismatch repair genes. The objective of this study was to determine the prevalence of LS in colorectal tumors during the first 15-months after the implementation of universal tumor-based screening for LS in Puerto Rico.
Methods
A total of 317 colorectal tumors were evaluated in a large private pathology laboratory from September 2014 to December 2015. Clinical characteristics were obtained from the pathology reports. Unadjusted and adjusted logistic regression models were used to estimate the magnitude of association (odds ratio OR with 95% confidence intervals CI) between absent MMR protein expression and patient characteristics.
Results
Most cases (93.4%) were analyzed by immunohistochemistry; 11.8% (35 of 296) had deficient mismatch repair protein expression. While 29 of the 317 cases were subjected to PCR-based microsatellite instability analysis of which 10.3% (3 of 317) had microsatellite instability. In total, 11.0% of the tumors were reported MMR deficient. These tumors were more likely from females and more likely localized in the proximal colon compared to those with proficient MMR expression.
Conclusions
Our data is consistent with the results from other studies including US Hispanics, where approximately 10% of Hispanic individuals with colorectal cancer have microsatellite instability. Our results support universal tumor-based screening for LS among Hispanics in accordance with National Comprehensive Cancer Network guidelines.
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.
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.
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.
Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and
and
mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests.
Of the 718 tumors analyzed, 34.2% (
= 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (
= 192), 3.2% had MSI, 9.7% had
, and 31.9% had
mutations. The most common
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.
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.
Abstract
Colorectal cancer (CRC) is the 1st cause of cancer-related deaths in Puerto Rico (PR). CRC is a heterogeneous disease with lifestyle and environmental factors shown to modify the risk to ...develop this disease. High intake of red and processed meats was determined to be a risk factor for increased risk of CRC. Genetic variations in genes involved in the metabolism of meat carcinogens have been found to be associated with CRC risk and to vary across racial/ethnic populations. The objective of this project was to determine the association of functional genetic variants in meat-carcinogen metabolism genes with CRC risk in the PR population. First, we analyzed the allelic frequencies of SNPs in key meat carcinogen metabolism genes (CYP1A1, CYP1B1, NAT2 and CYP2E1), that were previously reported to have an association with development of colorectal adenomas or CRC were evaluated in the 1000 Genomes Populations. The 1000 Genomes populations included AFR (African Populations), EUR (European Populations), CLM (Colombians from Medellin, Colombia), MXL (Mexican Ancestry from Los Angeles USA), PEL (Peruvians from Lima Peru) and PUR (Puerto Ricans from Puerto Rico). Then, we genotyped using TaqMan technology 5 functional SNPs localized at key meat carcinogen detoxifying genes, CYP1A1, CYP1B1, NAT1, NAT2 and CYP2E1 in Puerto Ricans (205 CRC cases and 218 controls). Our preliminary results showed that the allelic frequencies of the SNPs differ between PUR and the other 1000 Genomes populations, suggesting that these SNPs might have a distinct effect on the association of red/processed meat intake and CRC risk on Puerto Ricans. Furthermore, genotyping analysis showed that individuals with the AA genotype at the rs1800440 SNP (CYP1B1) who consume processed meat 2-4 times per week were at increased risk of CRC (p=0.008). These preliminary data support a role for genetic variants in genes that play key roles in the mechanisms of meat carcinogenesis as possible modifiers of the carcinogenic effects of meat.
Citation Format: Julyann Perez-Mayoral, Maria E. Perez-Hernandez, Mariana Stern, Marcia R. Cruz-Correa. Polymorphism in CYP1B1 increases CRC risk in Puerto Rican individuals that consume processed meats abstract. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C045.
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