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.
Background: Colorectal cancer (CRC) is the second and third most common diagnosed cancer in males and females, respectively, and is the second leading cause of cancer-related deaths in Puerto Rico (PR). This differs from USA, were CRC is the third most commonly diagnosed cancer and the third leading cause of cancer-related deaths for men and woman, respectively. CRC is a heterogeneous disease and the genetic characteristics of the tumors are considered to evaluate prognostic outcome and selection of targeted therapies. Currently, techniques such as next-generation sequencing (NGS) are being used for tumor profiling, in order to classify and identify driver genetic mutations in CRC patients. Even though there have been numerous studies that have use genetic profiling to classify and to identify driver genetic mutations for CRC, comprehensive genetic profiling of cancer patients in the Hispanic population of PR has not been performed. Methods: We retrospectively evaluated the mutational profile of CRC tumors from 218 Puerto Rican Hispanics (PRH) that underwent NGS testing from 2015 to 2020. The data was provided by CARIS Life Sciences that uses a 592 gene panel in order to detect mutations, indels and copy number variants (CNV). We estimated the prevalence of somatic mutations of PRH CRC tumors and compared them with the mutational profiles reported for Colorectal Adenocarcinoma from the TCGA Pan-Cancer Clinical Data available in the cBioPortal for Cancer Genomics. Descriptive statistics were performed to characterize the database. Results: For our population, 7.8% were diagnosed with CRC before 50 years of age (early-onset CRC) and 92.2% were diagnosed after 50 years of age. These analyses showed that the most commonly mutated genes for CRC tumors in PRH are APC (82%), TP53 (76%), KRAS (56%), PIK3CA (18%), SMAD4 (13%), AMER1 (10%), FBXW7 (9%), BRAF (5%), RNF43 (4%), and MUTYH (4%). Several genes are shared among the top ten most mutated genes when comparing the CRC tumor mutational profiles from PRH with that reported in the CRC tumors from TCGA study, including APC, TP53, KRAS, and PIK3CA, having mutational frequencies of 73%, 59%, 41%, and 28%, respectively. The most common CNVs for PRH CRC tumors were CDX2 (20%), CDKN1B (7%), and HNRNPA2B1 (5%) genes. These CNVs have also been reported in the CRC TCGA Pan-Cancer study with frequencies of 6.4%, 0.3% and 0.3 % for CDX2, CDKN1B, and HNRNPA2B1 genes, respectively. Conclusion: This study is the first to reports the mutational profile of CRC tumors from Puerto Rican Hispanics. CRC tumors from PRH and the TCGA study, which has only 0.8% of Hispanic/Latino patients, share mutated genes and CNV, although with different mutational frequencies. Understanding the most common carcinogenic molecular pathways that affect PRH with CRC is crucial to guide research efforts in the discovery of new therapeutic modalities. Citation Format: Ingrid M. Montes-Rodriguez, Hilmaris Centeno-Girona, Camila Rivera-Lynch, Marievelisse Soto-Salgado, Noridza Rivera, Marcia Cruz-Correa. Interrogating the molecular profile of colorectal cancer tumors in Puerto Rican Hispanics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 612.
Backgorund: Colorectal cancer (CRC) is among the leading causes of cancerrelated deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients. Methods: We conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next-generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan-Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)-Non-Hispanic, and GENIE-Hispanic datasets.Results: Among the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE-Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability-high (MSI), wild-type KRAS, wild-type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients. Conclusion:This is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non-Hispanic and USH populations.
Introduction: Colorectal cancer (CRC) is the 1st and 2nd leading cause of cancer death in men and women in Puerto Rico and the U.S., respectively. A dynamic balance between the host immune system and the gut bacterial communities is essential to protect colonic tissues against chronic inflammation, which may lead to CRC. The main goal of this study was to investigate if SNPs in the promoter regions of the IL-1β, IL-6 and IL-10, key cytokines that regulate gut inflammation, increase the risk for colorectal adenomas by enriching a subset of the toxin-producing gut microbiota (gene-environment interaction). Methods: Using a case-control study design, associations between having pro-inflammatory SNPs and/or bacterial toxins in colonic mucosa or stool were assessed using odds ratios. TaqMan® SNP Genotyping Assays (ThermoFisher Scientific) for IL- 1β (rs1143627), IL-6 (rs1800795), and IL-10 (rs1800871) were performed according to the manufacturer’s recommendations. The presence of bacterial toxin genes (pks, TcPC, GelE, cnf-1, CDT, murB, and usp) in stool were determined using the QuantiTect SYBR Green PCR kit (QIAGEN). Results: Our preliminary analyses showed that individuals with the IL-1β pro-inflammatory genotype were 1.5-times more likely to have colorectal adenomas (n=232; p=0.1). Detection of usp or pks in stool (n=147) was positively associated with having adenomas (OR=2.95; CI 95%= 0.92-9.45 and OR=2.91; CI 95%=0.58-14.50, respectively). Conclusion: An evaluation of the association between having pro-inflammatory genotypes, the presence of bacterial toxin genes in stool, and colorectal adenomas using a larger sample size is warranted and currently underway. The integration of modifiable (e.g. gut bacterial toxins) and non-modifiable (e.g. host genetics) risk factors in a stratified model for CRC risk stratification and/or prevention may enhance current screening approaches. Citation Format: Ibis R. Vera-Urbina, Estefania Ayala, Ediel Rodriguez, Hilmaris Centeno-Girona, Leslie Casiano, Belisa Suarez, Marcia Cruz-Correa, Maria Gonzalez-Pons. Host genetic susceptibility to gut microbiota-driven colorectal carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3526.
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