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Background: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene. Patients with FAP have multiple extraintestinal manifestations that follow a genotype-phenotype pattern; however, few data exist characterizing their cognitive abilities. Given the role of the APC protein in development of the central nervous system, we hypothesized that patients with FAP would show differences in cognitive functioning compared to controls. Methods: Matched case-control study designed to evaluate cognitive function using the Test of Nonverbal Intelligence-4, the Bateria III Woodcock-Munoz, and the Behavior Rating Inventory of Executive Functions-Adult. Twenty-six individuals with FAP (mean age = 34.2 ± 15.0 years) and 25 age-gender and educational level matched controls (mean age = 32.7 ± 13.8 years) were evaluated. Results: FAP-cases had significantly lower IQ (p = 0.005). Across all tasks of the Batería III Woodcock-Muñoz, FAP-cases performed significantly lower than controls, with all of the summary scores falling in the bottom quartile compared to controls (p < 0.0001). Patients with FAP scored within the deficient range for Long-Term Retrieval and Cognitive Fluency. Conclusion: APC protein has an important role in neurocognitive function. The pervasive nature of the observed cognitive dysfunction suggests that loss or dysfunction of the APC protein impacts processes in cortical and subcortical brain regions. Additional studies examining larger ethnically diverse cohorts with FAP are warranted. [ABSTRACT FROM AUTHOR]

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. [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]

The objective of this study was to compare the prevalence of Helicobacter pylori (HP) seropositivity in patients undergoing bariatric surgery with that of the general population. H. pylori serologies, tested by ELISA, were collected on 240 morbidly obese patients seen at the Cleveland Clinic Florida and on 2444 randomly selected patients seen at the Cleveland Clinic Health System from 2003–2005. H. pylori prevalence was 61.3% in the bariatric surgery group versus 48.2% in the general population control group ( p < 0.001). Bariatric patients had a 1.7-fold increased likelihood of having HP when compared with controls (95% CI = 1.3–2.2). Age over 35 years was an independent risk factor for HP seropositivity ( p < 0.01) in both the bariatric and control groups. There was no association found between body mass index and seropositivity within the bariatric group. There was no significant association between seropositivity and gender ( p = 0.776). However, there was a significant association between seropositivity and race ( p < 0.01). African-Americans had four times more (OR = 4.05) probability of having HP seropositivity than Caucasians ( p < 0.01). Hispanics had almost three times (OR = 2.6) more probability of having HP seropositivity than Caucasians ( p < 0.01). The prevalence of HP seropositivity among bariatric patients is significantly higher than the general population control group. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Although ablation therapy may be useful in the treatment of Barrett’s esophagus, evidence of effectiveness is scarce, and little is known about current utilization of ablation. We aimed to determine whether the use of ablation was increasing in a cohort of gastroenterologists, and to identify physician beliefs and characteristics associated with ablation use.METHODS:We surveyed a national sample of gastroenterologists about ablation use, with an 18-month follow-up. The self-administered instrument included questions about demographic characteristics, attitudes about ablation therapy, and prior experience with ablation. Case scenarios were also included. We used logistic regression to identify factors associated with the use of ablation in patients with Barrett’s esophagus.RESULTS:Two hundred seventy-nine (50.3% of those eligible) responded to the baseline survey. Few agreed that ablation lowers the risk of adenocarcinoma (15%) or is supported by the medical literature (19%). However, 25% of respondents reportedly had used ablation at baseline, and this increased to 36% in the follow-up survey (p = 0.0003). The use of ablation was significantly associated with physician age greater than 54 yr (odds ratio [OR] = 2.77, 95% CI = 1.04–7.37) and the belief that ablation was used by colleagues (OR = 13.27, 95% CI = 4.44–39.64) or decreases medical costs (OR = 5.07, 95% CI = 1.00–25.74).CONCLUSIONS:Although few gastroenterologists agreed that ablation is effective, a significant proportion had adopted its use. There was a significant increase in ablation use during our study period, and the characteristic that was most strongly associated with ablation use was the belief that colleagues used it. [Copyright &y& Elsevier]

Examines physicians' awareness of agreement with and compliance with practice guidelines for the surveillance of patients with Barrett esophagus (BE). Approach to patients with BE before and after release of clinical practice guidelines; Inability of guideline awareness to predict compliance; Improvements to guideline adherence.

Loss of imprinting (LOI), an epigenetic alteration affecting the insulin-like growth factor II gene (IGF2), is found in normal colonic mucosa of about 30% of colorectal cancer (CRC) patients, but it is found in only 10% of healthy individuals. In a pilot study to investigate the utility of LOI as a marker of CRC risk, we evaluated 172 patients at a colonoscopy clinic. The adjusted odds ratio for LOI in lymphocytes was 5.15 for patients with a positive family history [95% confidence interval (95% CI), 1.70 to 16.96; probability P = 0.002], 3.46 for patients with adenomas (95% CI, 1.14 to 11.37; P = 0.026), and 21.7 for patients with CRC (95% CI, 3.48 to 153.6; P = 0.0005). LOI can be assayed with a DNA-based blood test, and it may be a valuable predictive marker of an individual's risk for CRC. [ABSTRACT FROM AUTHOR]

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]

Importance: Colorectal cancer (CRC) is the second-leading cause of cancer death in the United States. Screening can reduce CRC mortality and incidence, and numerous screening options, although available, complicate informed decision making. This review provides evidence-based tools for primary care physicians to identify patients with higher-than-average-risk and engage patients in informed decision making about CRC screening options.Observations: Recently, the US Preventive Services Task Force recommended any of 8 CRC screening approaches for average-risk individuals, beginning at age 50 years. Only 2 methods have been shown in randomized clinical trials to reduce mortality: fecal occult blood testing and flexible sigmoidoscopy. Of the 8 programs, screenings using the fecal immunochemical test annually and colonoscopy every 10 years are now the most commonly used tests in the United States and among the most effective in reducing CRC mortality as determined by decision models. With the exception of primary screening using colonoscopy, all of the other screening approaches have multiple steps. Adherence to each phase of a multistep program is critical to achieving maximal effectiveness of the screening program. It is likely that each of the recommended programs can reduce CRC mortality, but other key outcomes may differ such as lifetime burden of colonoscopy, complications, patient acceptance, and cost. Decisions about the timing of screening cessation should be individualized.Conclusions and Relevance: CRC screening is effective if patients adhere to the steps in each screening program. There is no evidence that one program is superior to another. Informed decision-making tools are provided to assist patients and clinicians with the goal of improving adherence to effective screening. [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]

: BackgroundCholecystectomy is effective therapy for chronic calculous cholecystitis (CCC). The long-term outcome of patients treated with cholecystectomy for chronic acalculous cholecystitis (CAC) is unknown.: MethodsA controlled, retrospective cohort study assessing biliary pain (preoperative and at follow-up) in postcholecystectomy patients with CAC or CCC was performed.: ResultsIn 19 CAC and with matched CCC control patients, the mean duration of symptoms before surgery was 38.3 months (95% CI, 16.4 to 60.2) and 8.1 months (95% CI, 5.4 to 10.8), respectively. The mean follow-up for both groups was 8.37 ± 1.13 years. Both groups benefited from cholecystectomy (P <0.001), and both were equally likely to be pain-free upon long-term follow-up (95% CAC versus 84% CCC, P >0.05).: ConclusionsThere was no difference in outcome between the groups after an average follow-up of 8.37 years. Postcholecystectomy patients with chronic cholecystitis and no gallstones have long-term, complete pain resolution, similar to patients with gallstones. [Copyright &y& Elsevier]

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]

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries. • In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for Lynch syndrome (LS). LS screening is inconsistently applied within Latin America healthcare systems as the structure of the healthcare differed between the countries. • Path_MMR variants were described in 459 of 1352 (34%) families tested, most of which in the MLH1 or MSH2 genes followed by PMS2. • Path_MLH1 variants showed predominance in males, while path_MSH6 variants were higher in female carriers. • The countries with well-functioning systems may serve as healthcare models for other forms of inherited cancers. [ABSTRACT FROM AUTHOR]

The article discusses guidelines of the American Society of Clinical Oncology (ASCO) on early detection of colorectal cancer and management of any polyps found during colorectal cancer screening. It is evident that ASCO adopted an evidence-based approach for recommending cancer control priorities. It also analyzes method to consider optimal treatment of patients with early stage colorectal cancer.

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]

Abstract: 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. [ABSTRACT FROM AUTHOR]

In Puerto Rico, colorectal cancer (CRC) incidence and mortality rates are increasing. Moreover, adherence rates to CRC screening (52.2%) are still below the goals (70.5%) established by Healthy People 2020. Lack of knowledge is described as a significant barrier to adherence to CRC screening. The aim of this study was to assess CRC knowledge and screening rates among Puerto Rican Hispanics. Participants aged 40-85 years were recruited from the internal medicine outpatient clinics at the University of Puerto Rico. Demographic characteristics and knowledge about CRC, including risk factors and CRC screening tests, were obtained through face-to-face interviews. A mean CRC knowledge score was calculated based on correct responses to 13 validated questions. Mean knowledge scores were evaluated according to demographic characteristics using the Wilcoxon-Mann-Whitney test. A total of 101 participants were recruited with mean age of 63 (±10.6) years. Fifty-eight (58%) of participants were females, 59% reported ≥12 years of education, and 71% reported ever screening for CRC. The mean CRC knowledge score was significantly lower (p < 0.05) among participants with lower annual family income, those who had never received a recommendation for CRC screening by a healthcare provider, and those who had no history of CRC screening. Knowledge about CRC must be improved in Puerto Rico. Efforts must be made to promote and develop culturally appropriate CRC educational strategies. Future studies should focus on identifying other barriers and factors that may limit CRC screening in the Puerto Rican Hispanic population. [ABSTRACT FROM AUTHOR]

Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is caused by mismatch repair (MMR) gene mutations. However, data about MMR mutations in Hispanics are limited. This study aims to describe the spectrum of MMR mutations in Hispanics with LS and explore ancestral origins. This case series involved an IRB-approved retrospective chart review of self-identified Hispanic patients (n = 397) seen for genetic cancer risk assessment at four collaborating academic institutions in California, Texas, and Puerto Rico who were evaluated by MMR genotyping and/or tumor analysis. A literature review was conducted for all mutations identified. Of those who underwent clinical genetic testing (n = 176), 71 had MMR gene mutations. Nine mutations were observed more than once. One third (3/9) of recurrent mutations and two additional mutations (seen only once) were previously reported in Spain, confirming the influence of Spanish ancestry on MMR mutations in Hispanic populations. The recurrent mutations identified (n = 9) included both previously reported mutations as well as unique mutations not in the literature. This is the largest report of Hispanic MMR mutations in North America; however, a larger sample and haplotype analyses are needed to better understand recurrent MMR mutations in Hispanic populations. [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]

Background: Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas.Methods: We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist's recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy.Results: Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events.Conclusions: Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.). [ABSTRACT FROM AUTHOR]

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 ± 11.9 years, 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. [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]

Objective Serrated (hyperplastic) polyposis (SP) is a rare disorder with multiple colorectal hyperplastic polyps and often sessile serrated adenomas/polyps (SSA/P) or adenomas. Although associated with colorectal cancer, the course of SP is not well described. Design 44 patients with SP were studied. The results of 146 colonoscopies with median follow-up of 2.0 years (range 0-30) and a median of 1.0 years (range 0.5-6) between surveillance colonoscopies were evaluated. Findings from oesophogastroduodenoscopy examinations were analysed. Results The mean age at diagnosis of SP was 52.5±11.9 years (range 22-78). In two pedigrees (5%) another family member had SP. None of 22 patients had gastroduodenal polyps. All patients had additional colorectal polyps at surveillance colonoscopy. SSA/P or adenomas were found in 25 patients (61%) at first colonoscopy and 83% at last colonoscopy. Recurrent SSA/P or adenomas occurred in 68% of patients at surveillance colonoscopy. Three patients had colorectal cancer. Eleven patients (25%) underwent surgery (mean time from diagnosis of SP 2.0±0.9 years). After surgery all seven surveyed patients developed recurrent polyps in the retained colorectum (4/7 had SSA/P or adenomas). No association was found between colorectal neoplasia and sex, age at diagnosis of SP or initial number of colorectal polyps. Conclusions In SP, rapid and unrelenting colorectal neoplasia development continues in the intact colorectum and retained segment after surgery. These findings support the possibility of annual colonoscopic surveillance, consideration for colectomy when SSA/P or adenomas are encountered and frequent postoperative endoscopic surveillance of the retained colorectum. [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]

The article presents a study that calculates annual percentage changes (APC) and relative risks (RR) to colorectal cancer (CRC) patients in the U.S. and Puerto Rico (PR). The study shows that during 1998 through 2002, the CRC and APC incidence and mortality raised for men in PR on the other hand, declining trends were discovered for other racial groups. Overall period rated showed that Puerto Ricans had CRC mortality and incidence rates were the same to those for U.S. Hispanics.

Background: Juvenile polyposis (JP) is an autosomal-dominant syndrome characterised by the development of hamartomatous gastrointestinal polyps and is associated with colorectal cancer. However, the relative and absolute risk of colorectal malignancy in these patients is not known. Methods: The incidence rates of colorectal cancer in patients with JP were compared with that of the general population through person-year analysis with adjustment for demographics. Results: In patients with JP, the RR (95% CI) of colorectal cancer was 34.0 (14.4 to 65.7). Similar risks were noted in both males (30.0, 9.6 to 68.6) and females (43.7, 8.8 to 125). The cumulative life-time risk for colorectal cancer was 38.7%. The mean (SD) age of diagnosis of colorectal cancer was 43.9 (10.4) years. Other gastrointestinal malignancies were not noted in this cohort. Conclusion: Patients with JP have a markedly increased RR and absolute risk for colorectal cancer and require vigilant colorectal surveillance starting at young age. A low threshold for recommending surgery with consideration for removal of the entire colorectum seems warranted. [ABSTRACT FROM AUTHOR]