Background: The ATP-binding cassette (ABC) superfamily is one of the largest evolutionarily conserved families of proteins. ABC proteins play key roles in cellular detoxification of endobiotics and xenobiotics. Overexpression of certain ABC proteins, among them the multidrug resistance associated protein (MRP), contributes to drug resistance in organisms ranging from human neoplastic cells to parasitic protozoa. In the present study, thePlasmodium berghei mrpgene (pbmrp) was partially characterized and the predicted protein was classified using bioinformatics in order to explore its putative involvement in drug resistance.Methods: Thepbmrpgene from theP. bergheidrug sensitive, N clone, was sequenced using a PCR strategy. Classification and domain organization of pbMRP were determined with bioinformatics. ThePlasmodium spp.MRPs were aligned and analysed to study their conserved motifs and organization. Gene copy number and organization were determined via Southern blot analysis in both N clone and the chloroquine selected line, RC. Chromosomal Southern blots and RNase protection assays were employed to determine the chromosomal location and expression levels ofpbmrpin blood stages.Results: Thepbmrpgene is a single copy, intronless gene with a predicted open reading frame spanning 5820 nucleotides. Bioinformatic analyses show that this protein has distinctive features characteristic of the ABCC sub-family. Multiple sequence alignments reveal a high degree of conservation in the nucleotide binding and transmembrane domains within the MRPs from thePlasmodium spp.analysed. Expression ofpbmrpwas detected in asexual blood stages. Gene organization, copy number and mRNA expression was similar in both lines studied. A chromosomal translocation was observed in the chloroquine selected RC line, from chromosome 13/14 to chromosome 8, when compared to the drug sensitive N clone.Conclusion: In this study, thepbmrpgene was sequenced and classified as a member of the ABCC sub-family. Multiple sequence alignments reveal that this gene is homologous to thePlasmodium y. yoeliiandPlasmodium knowlesi mrp, and thePlasmodium vivaxandPlasmodium falciparum mrp2genes. There were no differences in gene organization, copy number, or mRNA expression between N clone and the RC line, but a chromosomal translocation ofpbmrpfrom chromosome 13/14 to chromosome 8 was detected in RC.
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.
21 January 2017 in Hereditary Cancer in Clinical Practice
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.
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.
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.
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.