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Backgorund: Colorectal cancer (CRC) is among the leading causes of cancer-related 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Author(s): Marcia Cruz-Correa[sup.1,2,8] , Julyann Pérez-Mayoral[sup.1,2] , Julie Dutil[sup.3] , Miguel Echenique[sup.4] , Rafael Mosquera[sup.5] , Keila Rivera-Román[sup.6] , Sharee Umpierre[sup.1] , Segundo Rodriguez-Quilichini[sup.1] , Maria Gonzalez-Pons[sup.1,2] , Myrta I. [...]

Abstract Background Activating KRAS mutations are important for cancer initiation and progression; and have recently been shown to cause primary resistance to therapies targeting the epidermal growth factor receptor. Therefore, strategies are currently in development to overcome treatment resistance due to oncogenic KRAS. The hypoxia-inducible factors-1α and -2α (HIF-1α and HIF-2α) are activated in cancer due to dysregulated ras signaling. Methods To understand the individual and combined roles of HIF-1α and HIF-2α in cancer metabolism and oncogenic KRAS signaling, we used targeted homologous recombination to disrupt the oncogenic KRAS, HIF-1α, and HIF-2α gene loci in HCT116 colon cancer cells to generate isogenic HCT116WT KRAS, HCT116HIF-1α-/-, HCT116HIF-2α-/-, and HCT116HIF-1α-/-HIF-2α-/- cell lines. Results Global gene expression analyses of these cell lines reveal that HIF-1α and HIF-2α work together to modulate cancer metabolism and regulate genes signature overlapping with oncogenic KRAS. Cancer cells with disruption of both HIF-1α and HIF-2α or oncogenic KRAS showed decreased aerobic respiration and ATP production, with increased ROS generation. Conclusion Our findings suggest novel strategies for treating tumors with oncogenic KRAS mutations.

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. [ABSTRACT FROM AUTHOR]

There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA-African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA. [ABSTRACT FROM AUTHOR]

PURPOSE: To provide resource-stratified, evidence-based recommendations on the treatment and follow-up of patients with early-stage colorectal cancer. METHODS: ASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus process with additional experts for one round of formal ratings. RESULTS: Existing sets of guidelines from 12 guideline developers were identified and reviewed; adapted recommendations from six guidelines form the evidence base and provide evidence to inform the formal consensus process, which resulted in agreement of 75% or more on all recommendations. RECOMMENDATIONS: For nonmaximal settings, the recommended treatments for colon cancer stages nonobstructing, I-IIA: in basic and limited, open resection; in enhanced, adequately trained surgeons and laparoscopic or minimally invasive surgery, unless contraindicated. Treatments for IIB-IIC: in basic and limited, open en bloc resection following standard oncologic principles, if not possible, transfer to higher-level facility; in emergency, limit to life-saving procedures; in enhanced, laparoscopic en bloc resection, if not possible, then open. Treatments for obstructing, IIB-IIC: in basic, resection and/or diversion; in limited or enhanced, emergency surgical resection. Treatment for IIB-IIC with left-sided: in enhanced, may place colonic stent. Treatment for T4N0/T3N0 high-risk features or stage II high-risk obstructing: in enhanced, may offer adjuvant chemotherapy. Treatment for rectal cancer cT1N0 and cT2n0: in basic, limited, or enhanced, total mesorectal excision principles. Treatment for cT3n0: in basic and limited, total mesorectal excision, if not, diversion. Treatment for high-risk patients who did not receive neoadjuvant chemotherapy: in basic, limited, or enhanced, may offer adjuvant therapy. Treatment for resectable cT3N0 rectal cancer: in enhanced, base neoadjuvant chemotherapy on preoperative factors. For post-treatment surveillance, a combination of medical history, physical examination, carcinoembryonic antigen testing, imaging, and endoscopy is performed. Frequency depends on setting. Maximal setting recommendations are in the guideline. Additional information can be found at www.asco.org/resource-stratified-guidelines. NOTICE: It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guidelines are intended to complement but not replace local guidelines. [ABSTRACT FROM AUTHOR]

Background: Late stage at diagnosis of cancer is considered a key predictor factor for a lower survival rate. Knowing and understanding the barriers to an early diagnosis of colorectal cancer is critical in the fight to reduce the social and economic burden caused by cancer in Puerto Rico. This study evaluates factors associated to colorectal cancer stage at diagnosis among Puerto Rico's Government Health Plan (GHP) patients.Methods: We conducted a cross-sectional study based on a secondary data analysis using information from the Puerto Rico Central Cancer Registry (PRCCR) and the Puerto Rico Health Insurance Administration (PRHIA). Logistic regression models were used to estimate the unadjusted odds ratio (ORs) and adjusted odds ratio (AORs), and their 95 % confidence intervals (CIs). Colorectal cancer cases diagnosed between January 1, 2012 and December 31, 2012, among persons 50 to 64 years of age, participants of the GHP and with a cancer diagnosis reported to the PRCCR were included in the study.Results: There were 68 (35.79 %) colorectal cancer patients diagnosed at early stage while 122 (64.21 %) where diagnosed at late stage. In the multivariate analysis having a diagnostic delay of more than 59 days (AOR 2.94, 95 % CI: 1.32 to 6.52) and having the first visit through the emergency room (AOR 3.48, 95 % CI: 1.60 to 7.60) were strong predictors of being diagnosed with colorectal cancer at a late stage.Conclusions: These results are relevant to understand the factors that influence the outcomes of colorectal cancer patients in the GHP. Therefore, it is important to continue developing studies to understand the Government Health Plan patient's pathways to a cancer diagnosis, in order to promote assertive decisions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Colorectal cancer represents a major health problem and an important economic burden in Puerto Rico. In the 1990's, the Commonwealth of Puerto Rico implemented a health care reform through the privatization of the public health system. The goal was to ensure access to health services, eliminate disparities for medically indigent citizens and provide special coverage for high-risk conditions such as cancer. This study estimates the 5-year relative survival rate of colorectal cancer and the relative excess risk of death in Puerto Rico for 2004–2005, by type of health insurance coverage; Government Health Plan vs. Non-Government Health Plan. Colorectal cancer in advanced stages was more common in Government Health Plan patients compared with Non-Government Health Plan patients (44.29% vs. 40.24 had regional extent and 13.58% versus 10.42% had distant involvement, respectively). Government Health Plan patients in the 50–64 (RR = 6.59; CI: 2.85–15.24) and ≥65 (RR = 2.4; CI: 1.72–4.04) age-groups had the greater excess risk of death compared with Non-Government Health Plan patients. Further studies evaluating the interplay of access to health services and the barriers affecting the Government Health Plan population are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Activating KRAS mutations are important for cancer initiation and progression; and have recently been shown to cause primary resistance to therapies targeting the epidermal growth factor receptor. Therefore, strategies are currently in development to overcome treatment resistance due to oncogenic KRAS. The hypoxiainducible factors-1α and -2α (HIF-1α and HIF-2α) are activated in cancer due to dysregulated ras signaling. Methods: To understand the individual and combined roles of HIF-1α and HIF-2α in cancer metabolism and oncogenic KRAS signaling, we used targeted homologous recombination to disrupt the oncogenic KRAS, HIF-1α, and HIF-2α gene loci in HCT116 colon cancer cells to generate isogenic HCT116WT KRAS, HCT116HIF-1α-/-, HCT116HIF- 2α-/-, and HCT116HIF-1α-/-HIF-2α-/- cell lines. Results: Global gene expression analyses of these cell lines reveal that HIF-1α and HIF-2α work together to modulate cancer metabolism and regulate genes signature overlapping with oncogenic KRAS. Cancer cells with disruption of both HIF-1α and HIF-2α or oncogenic KRAS showed decreased aerobic respiration and ATP production, with increased ROS generation. Conclusion: Our findings suggest novel strategies for treating tumors with oncogenic KRAS mutations. [ABSTRACT FROM AUTHOR]

Epidemiologic and experimental reports suggest that female hormones protect against the development of colorectal cancer, but studies are limited. We describe a patient in the placebo arm of a 4-year primary chemoprevention trial who developed adenomatous polyps and then had eradication of polyps after the administration of oral contraceptives. No change in the prostaglandin levels in the colonic mucosa was noted after polyp elimination, making nonsteroidal anti-inflammatory drug ingestion unlikely as a cause. This report represents the regression of colorectal adenomas with the use of estrogen/progesterone compounds. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Background & Aims Endoscopists do not routinely follow guidelines to survey individuals with low-risk adenomas (LRAs; 1–2 small tubular adenomas, < 1 cm) every 5–10 years for colorectal cancer; many recommend shorter surveillance intervals for these individuals. We aimed to identify the reasons that endoscopists recommend shorter surveillance intervals for some individuals with LRAs and determine whether timing affects outcomes at follow-up examinations. Methods We collected data from 1560 individuals (45–75 years old) who participated in a prospective chemoprevention trial (of vitamin D and calcium) from 2004 through 2008. Participants in the trial had at least 1 adenoma, detected at their index colonoscopy, and were recommended to receive follow-up colonoscopy examinations at 3 or 5 years after adenoma identification, as recommended by the endoscopist. For this analysis we collected data from only participants with LRAs. These data included characteristics of participants and endoscopists and findings from index and follow-up colonoscopies. Primary endpoints were frequency of recommending shorter (3-year) vs longer (5-year) surveillance intervals, factors associated with these recommendations, and effect on outcome, determined at the follow-up colonoscopy. Results A 3-year surveillance interval was recommended for 594 of the subjects (38.1%). Factors most significantly associated with recommendation of 3-year vs a 5-year surveillance interval included African American race (relative risk [RR] to white, 1.41; 95% confidence interval [CI], 1.14–1.75), Asian/Pacific Islander ethnicity (RR to white, 1.7; 95% CI, 1.22–2.43), detection of 2 adenomas at the index examination (RR vs 1 adenoma, 1.47; 95% CI, 1.27–1.71), more than 3 serrated polyps at the index examination (RR=2.16, 95% CI, 1.59–2.93), or index examination with fair or poor quality bowel preparation (RR vs excellent quality, 2.16; 95% CI, 1.66–2.83). Other factors that had a significant association with recommendation for a 3-year surveillance interval included family history of colorectal cancer and detection of 1–2 serrated polyps at the index examination. In comparisons of outcomes, we found no significant differences between the 3-year vs 5-year recommendation groups in proportions of subjects found to have 1 or more adenomas (38.8% vs 41.7% respectively; P = .27), advanced adenomas (7.7% vs 8.2%; P = .73) or clinically significant serrated polyps (10.0% vs 10.3%; P = .82) at the follow-up colonoscopy. Conclusions Possibly influenced by patients’ family history, race, quality of bowel preparation, or number or size of polyps, endoscopists frequently recommend 3-year surveillance intervals instead of guideline-recommended intervals of 5 years or longer for individuals with LRAs. However, at the follow-up colonoscopy, similar proportions of participants have 1 or more adenomas, advanced adenomas, or serrated polyps. These findings support the current guideline recommendations of performing follow-up examinations of individuals with LRAs at least 5 years after the index colonoscopy. [ABSTRACT FROM AUTHOR]