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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]

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]

Familial adenomatous polyposis (FAP) is an inherited form of colorectal cancer characterized by hundreds of adenomatous polyps in the colon and rectum. FAP is also associated with thyroid cancer (TC), but the lifetime risk is still unclear. This study reports the standardized incidence ratio (SIR) of TC in Hispanic FAP patients. TC incidence rates in patients with FAP between the periods of January 1, 2006 to December 31, 2013 were compared with the general population through direct database linkage from the Puerto Rico Central Cancer Registry (PRCCR) and the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). The study population consisted of 51 Hispanic patients with FAP and 3239 with TC from the general population. The SIR was calculated using the Indirect Method, defined as observed TC incidence among patients with FAP in PURIFICAR's cohort (2006-2013) divided by the expected TC incidence based on the PR population rates (2006-2010). SIR values were estimated by sex (male, female, and overall). This study received IRB approval (protocol #A2210207). In Hispanic patients with FAP, the SIR (95 % CI) for TC was 251.73 (51.91-735.65), with higher risk for females 461.18 (55.85-1665.94) than males 131.91 (3.34-734.95). Hispanic FAP patients are at a high risk for TC compared to the general population. Our incidence rates are higher than previous studies, suggesting that this community may be at a higher risk for TC than previously assumed. Implementation of clinical surveillance guidelines and regular ultrasound neck screening in Hispanic FAP patients is recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Several genetically defined hereditary colorectal cancer (CRC) syndromes are associated with colonic polyposis including familial adenomatous polyposis (FAP) and MUTYH adenomatous polyposis (MAP). Limited data exists on the clinical characterization and genotypic spectrum of polyposis syndromes among Hispanics. To describe the phenotype and genotype of Puerto Rican Hispanic patients with FAP and MUTYH and compare with other ethnic and racial groups. Probands were identified from the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Recruited individuals completed risk factors, medical, and family history questionnaires and underwent genetic testing for genotype analysis. Frequency analysis, Chi square, Fisher's exact and Wilcoxon rank-sum tests were used for statistical analysis methods. A total of 31 FAP (from 19 families) and 13 MAP (from 13 families) Hispanic patients recruited from the PURIFICAR were evaluated. Among the FAP cases, mean age at diagnosis was 27.6 (range 9-71 years); 67.7 % cases had more than 100 polyps and 41.9 % had upper gastrointestinal polyps. Among the 19 FAP families, there were 77 affected FAP individuals and 26 colorectal cancer cases. Genetic mutations were available for 42.2 % of FAP families; all mutations identified were unique. Surgeries were reported in 31 cases; 14 (45.2 %) prophylactic surgeries and 6 (19.4 %) therapeutic surgeries for management of CRC. Among MAP cases, mean age at diagnosis was 53 (range 34-76 years). Genetic analysis revealed homozygous biallelic mutations (G382D) in 53.8 %, compound heterozygous mutations (G382/Y165C) in 23 %, and non-G382/Y165C monoallelic mutations in 23 %. Familial cancer registries should be promoted as vehicles for detection, education and follow up of families at-risk of acquiring familial cancers. PURIFICAR is the first and only familial cancer registry in Puerto Rico providing these services to families affected with familial cancer syndromes promoting education, testing and surveillance of at-risk family members, and focusing on cancer prevention efforts. The fact that only 40 % of FAP patients had access to genetic testing stresses the need to promote the establishment of policies supporting genetic testing coverage by medical insurance companies in order to provide patients with the highest standard of care to prevent cancer. Furthermore, our results suggest that Hispanics may have uncommon mutations in adenomatous polyposis related genes, which emphasize the need for full gene sequencing to establish genetic diagnosis. [ABSTRACT FROM AUTHOR]

Familial adenomatous polyposis (FAP) is an autosomal dominant disease with hundreds of colorectal adenomas in teenagers and progression to colorectal cancer if colectomy is not performed. We investigated the association of two phenotypic manifestations-oral mucosal vascular density (OMVD) and oral mucosal reflectance (OMR)--with FAP and patients with multiple colorectal adenomas. Thirty-three patients with FAP from 29 unrelated pedigrees with APC gene mutation, 5 with multiple adenomas and no known gene mutations, and 50 population controls were evaluated for the two different manifestations utilizing a photographic/spectrophotometric system capturing images and reflectance at various wavelengths. Statistical analysis was performed with student t test and test performance characteristics were calculated. There were no significant differences in demographic variables between the FAP and control group. A significant difference in OMVD between FAP patients and controls was noted, P < 0.001. The sensitivity and specificity of oral mucosal vascular density for FAP was 91 and 90%, respectively. No association between this phenotypic manifestation and age or gender was found. All 5 patient with multiple polyps were positive for OMVD and the value was significantly higher than controls, P = 0.002. No significant difference was noted in OMR between the two patient groups and controls. OMVD is a new phenotypic manifestation in patients with FAP and also may identify those with multiple adenomas without known gene mutation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location ( P = 0.02) and poor histological tumor differentiation ( P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks. [ABSTRACT FROM AUTHOR]

Serrated adenomas are categorized as sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs). SSAs are more prevalent in the proximal colon and lack classic dysplasia, whereas TSAs are more prevalent in the rectosigmoid and have cytologic dysplasia. Serrated adenomas may progress to colorectal adenocarcinoma through diverse molecular alterations. Colonoscopy is the only test for the early detection of serrated adenomas that allows inspection of the entire colon and same-session biopsy sampling or polypectomy, if necessary. If an endoscopic biopsy at the right colon reveals SSA without cytologic dysplasia or biopsy at the rectosigmoid reveals SSA or TSA, those polyps should be excised or surgically resected as necessary. Postpolypectomy surveillance for removed SSAs without dysplasia and TSAs must be performed at 5- and 3-year intervals, respectively, with colonoscopy to prevent recurrence and progression to colorectal adenocarcinoma. [ABSTRACT FROM AUTHOR]

The insulin-like growth factor 2 ( IGF2) gene is the first gene discovered to be imprinted and expressed exclusively from the paternal allele in both humans and mice. Similarly, IGF2 is the first imprinted gene displaying loss of imprinting (LOI) in human cancers. LOI of IGF2 results in activation of the normally silent maternal allele, with increased IGF2 expression and possible increased cancer risk. LOI occurs in colonic cancer tissues, matched normal tissues, and peripheral blood lymphocytes. Human studies have found a significant, independent, positive association between LOI of IGF2 and personal and family history of colorectal neoplasia. Furthermore, animal studies using a murine model of LOI of IGF2 support an increase in intestinal neoplasia risk and abnormal colonic mucosal differentiation. LOI of IGF2 appears to be associated with a human colorectal cancer phenotype involving younger age at diagnosis, more advanced disease, right-side colonic location, and poorly differentiated or mucinous carcinoma. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO), a potent nonadrenergic, noncholinergic mediator of gastrointestinal smooth muscle, causes relaxation of the category I pump like sphincter of Oddi (SO) (eg, opossum, rabbit) and category II resistor like SO (eg, pig, human). Topical administration of a NO donor induces SO relaxation in humans, and parenteral administration of sodium nitroprusside (SNP) decreases sphincter contractility in pig SO. The aim of this study is to evaluate the effect of intrasphincteric SNP injection on pig SO. Under general anesthesia, two pigs received intrasphincteric saline injection (1 ml) and six pigs received intrasphincteric SNP (0.5 µg/ml) injection into the SO. All injections were administered into the major papilla using a 5-mm sclerotherapy needle through the duodenoscope. Endoscopic biliary manometry was performed using the standard station pull-through technique and SO pressures were recorded before and after injection. Intrasphincteric saline injection did not significantly change the mean SO motility index (MI) (197 vs 198). However, intrasphincteric SNP reduced both the mean SO basal pressure (P = 0.002) and the mean SO MI (226 vs 109; P = 0.002). The effect of intrasphincteric SNP lasted up to 45 min and did not cause significant lowering of systemic blood pressure. This is the first study to demonstrate that intrasphincteric SNP results in significant reduction in both SO basal pressure and SO MI in the porcine model. The endoscopic intrasphincteric administration of NO donor drugs is technically feasible and without observed systemic side effects. KEY WORDS: sphincter of Oddi; motility; nitric oxide; manometry; intrasphincteric injection; pig. [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]