[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Familial Cancer 03/2015; 14(3). DOI:10.1007/s10689-015-9795-y · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Barrett's esophagus (BE) is the strongest risk factor of esophageal adenocarcinoma (EAC). A previous study found a lower incidence of EAC in Puerto Rico (PR) as compared to other racial/ethnic groups in the United States (US). Notwithstanding, BE epidemiology in PR is unknown. Study aims: i) to determine BE prevalence among individuals with gastroenterological pathology reports from three major anatomic pathology laboratories in PR and ii) to describe the association between dysplastic BE with age and gender.
Clinic-based study examined data collected from three anatomic pathology laboratories encompassing the majority of gastroenterology practices in PR. Individuals with histology confirmed BE (January 2007-December 2011) were analyzed (n = 1,232). We estimated BE prevalence and adjusted odds ratios (AOR) to assess magnitude of association between dysplastic BE with age and gender using logistic regression models.
Overall BE prevalence was 4.4% (95% CI = 4.1-4.6). Most BE patients were males (male-to-female ratio = 2.3:1) with mean age of 64 ± 13 years. Ninety one percent of BE biopsies showed no dysplasia whereas 6.2% had EAC. BE patients age > 74 years had an increased risk of EAC (AOR: 2.38, 95% CI = 1.14-4.94) compared to those < 55 years old. Males had increased EAC risk (AOR: 2.23, 95% CI = 1.23-4.06) compared to females.
BE prevalence in PR is similar to that of non-Hispanic whites and Hispanics in US. The lower occurrence of dysplastic BE in PR could explain EAC incidence disparities between PR and other groups in the US.
Puerto Rico health sciences journal 12/2014; 33(4):184-9. · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Gastroenterology Research and Practice 10/2014; 2014:527946. DOI:10.1155/2014/527946 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: & Aims: Obesity is associated with neoplasia, possibly via insulin-mediated cell pathways that affect cell proliferation. Metformin has been proposed to protect against obesity-associated cancers by decreasing serum insulin. We conducted a randomized, double-blind, placebo-controlled, phase 2 study of patients with Barrett's Esophagus (BE) to assess the effect of metformin on phosphorylated S6 kinase (pS6K1) -- a biomarker of insulin pathway activation.
[Show abstract][Hide abstract] ABSTRACT: Purpose of review:
Provide an evidence-based resource for the surveillance of gastrointestinal premalignant lesions, focusing on the scientific articles reported recently.
No randomized controlled clinical trials exist to definitively support the efficacy of surveillance programs for Barrett's esophagus and gastric intestinal metaplasia. However, surveillance of these premalignant lesions is recommended by some of the leading organizations. To optimize the usefulness of surveillance programs, targeting high-risk patients might maximize its benefits. A Barrett's esophagus segment of at least 3 cm and evidence of intestinal metaplasia can help stratify those patients at highest risk for progression to esophageal adenocarcinoma. The location, extent, and severity of intestinal metaplasia are indicators of risk of developing gastric cancer. Patients with extensive intestinal metaplasia should be offered endoscopic surveillance. Quality in the baseline colonoscopy is crucial to decrease the risk of interval colorectal cancers. The importance of serrated polyps, as well as their surveillance intervals, is emphasized.
To optimize the usefulness of surveillance programs, targeting high-risk patients might maximize its benefits. Future research is needed to design more effective surveillance strategies. Recently, emerging imaging techniques hold promise for improving sensitivity of endoscopic surveillance of premalignant conditions in the gastrointestinal tract.
Current Opinion in Gastroenterology 07/2014; 30(5). DOI:10.1097/MOG.0000000000000090 · 4.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
PLoS ONE 05/2014; 9(5):e96746. DOI:10.1371/journal.pone.0096746 · 3.23 Impact Factor