Implementation of Universal Colorectal Cancer Screening for Lynch Syndrome in Hispanics Living in Puerto Rico.

OBJECTIVE: Colorectal cancer is the leading cause of cancer death in Puerto Rico and third among Hispanics in the USA. Up to 2-4% of colorectal cancer cases are a result of Lynch syndrome (LS), a hereditary cancer syndrome caused by a germline mutation in at least one of the DNA mismatch repair genes. The objective of this study was to determine the prevalence of LS in colorectal tumors during the first 15-months after the implementation of universal tumor-based screening for LS in Puerto Rico. METHODS: A total of 317 colorectal tumors were evaluated in a large private pathology laboratory from September 2014 to December 2015. Clinical characteristics were obtained from the pathology reports. Unadjusted and adjusted logistic regression models were used to estimate the magnitude of association (odds ratio [OR] with 95% confidence intervals [CI]) between absent MMR protein expression and patient characteristics. RESULTS: Most cases (93.4%) were analyzed by immunohistochemistry; 11.8% (35 of 296) had deficient mismatch repair protein expression. While 29 of the 317 cases were subjected to PCR-based microsatellite instability analysis of which 10.3% (3 of 317) had microsatellite instability. In total, 11.0% of the tumors were reported MMR deficient. These tumors were more likely from females and more likely localized in the proximal colon compared to those with proficient MMR expression. CONCLUSIONS: Our data is consistent with the results from other studies including US Hispanics, where approximately 10% of Hispanic individuals with colorectal cancer have microsatellite instability. Our results support universal tumor-based screening for LS among Hispanics in accordance with National Comprehensive Cancer Network guidelines.

Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis.

BACKGROUND & AIMS: Familial adenomatous polyposis is an autosomal dominant disorder characterized by the development of hundreds of colorectal adenomas and eventually colorectal cancer. Oral administration of the spice curcumin has been followed by regression of polyps in patients with this disorder. We performed a double-blinded randomized trial to determine the safety and efficacy of curcumin in patients with familial adenomatous polyposis. METHODS: This study included 44 patients with familial adenomatous polyposis (18-85 years old) who had not undergone colectomy or had undergone colectomy with ileorectal anastomosis or ileal anal pouches, had at least 5 intestinal adenomatous polyps, and had enrolled in Puerto Rico or the United States from September 2011 through November 2016. Patients were randomly assigned (1:1) to groups given 100% pure curcumin (1,500 mg orally, twice per day) or identical-appearing placebo capsules for 12 months. The number and size of lower gastrointestinal tract polyps were evaluated every 4 months for 1 year. The primary outcome was the number of polyps in the curcumin and placebo groups at 12 months or at the time of withdrawal from the study according to the intention-to-treat principle. RESULTS: After 1 year of treatment, the average rate of compliance was 83% in the curcumin group and 91% in the placebo group. After 12 weeks, there was no significant difference in the mean number of polyps between the placebo group (18.6; 95% CI, 9.3-27.8) and the curcumin group (22.6; 95% CI, 12.1-33.1; P = .58). We found no significant difference in mean polyp size between the curcumin group (2.3 mm; 95% CI, 1.8-2.8) and the placebo group (2.1 mm; 95% CI, 1.5-2.7; P = .76). Adverse events were few, with no significant differences between groups. CONCLUSIONS: In a double-blinded randomized trial of patients with familial adenomatous polyposis, we found no difference in the mean number or size of lower intestinal tract adenomas between patients given curcumin 3,000 mg/day and those given placebo for 12 weeks. Clinicaltrials.gov ID NCT00641147.

Factors Associated With Shorter Colonoscopy Surveillance Intervals for Patients With Low-Risk Colorectal Adenomas and Effects on Outcome.

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.

Hereditary cancer syndromes in Latino populations: genetic characterization and surveillance guidelines.

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.

A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas.

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.).

Association between calcium intake and colorectal neoplasia in Puerto Rican Hispanics / Asociación entre el consumo de calcio y la neoplasia colorectal en hispanos puertorriqueños

Epidemiological studies show that a high calcium intake reduces the risk of colon cancer. The objective was to study the association between calcium intake and colorectal neoplasia in a clinic-based sample of Hispanics adults from Puerto Rico. As part of this cross-sectional study, a total of 433 subjects were recruited from surgery and gastroenterology clinics at the University of Puerto Rico. Calcium intake was estimated using a food frequency questionnaire (FFQ) of calcium rich foods. Socio-demographics, health history and colonoscopy results were obtained from the primary study. Chi square and odds ratios (OR) for colorectal neoplasia (adenomas and/or adenocarcinoma) were calculated for total calcium, dietary calcium and for calcium supplement use. In total, 312 (72%) from 433 participants completed the FFQ and had available colonoscopy results; from these, 196 (62.5%) were free of neoplasia and 117 (37.5%) had colorectal neoplasia. Colorectal neoplasia subjects were older, a lower proportion were females and less educated than those without neoplasia (p<0.01). Total calcium intake (median 1180 mg/d) was greater in those free of neoplasia compared to colorectal neoplasia subjects (median 1036 mg/d; p<0.05). A high total calcium intake and the use of calcium supplements significantly reduced the OR (crude and age adjusted) for colorectal neoplasia; although these associations lost statistical significance after additionally adjusting for gender and educational level. In conclusion, a high calcium intake and the use of calcium supplements may be protective against colorectal neoplasia, although a greater sample may be required to observe significant associations in a multivariate model.

Los estudios muestran que un alto consumo de calcio reduce el riesgo de cáncer de colon. El objetivo del presente estudio fue estudiar la asociación entre el consumo de calcio y la neoplasia colorrectal en una muestra de hispanos adultos en Puerto Rico. Un total de 433 sujetos fueron reclutados de las clínicas de cirugía y gastroenterología de la Universidad de Puerto Rico. El consumo de calcio fue estimado usando un cuestionario de frecuencia de consumo (CFC) de alimentos ricos en calcio. Los datos socio-demográficos y la colonoscopia se obtuvieron del estudio principal. Se calculó el Ji² y la razón de productos cruzados de neoplasia colorrectal por el consumo total, dietético y uso de suplementos de calcio. Un total de 312 (72%) de 433 participantes completaron el estudio; de éstos, 196 (62.5%) estaban libres de neoplasia y 117 (37.5%) tenían neoplasia colorrectal, los cuales eran de mayor edad, con menor proporción de mujeres y menos educados que aquellos sin neoplasia (p<0.01). El consumo total de calcio (mediana 1180 mg/d) fue mayor en sujetos sin neoplasia que los sujetos con neoplasia (mediana 1036 mg/d; p<0.05). Un alto consumo total de calcio y el uso de suplementos de calcio redujo significativamente la posibilidad (crudo y ajustado por edad) de neoplasia colorrectal; aunque no fue significativo cuando se ajusto también por género y educación. En conclusión, un alto consumo de calcio y el uso de suplementos de calcio pueden proteger contra la neoplasia colorrectal, aunque se requieren más sujetos para ver asociaciones significativas en el modelo multivariado.

Is barium enema an adequate diagnostic test for the evaluation of patients with positive fecal occult blood?

BACKGROUND: This study aimed to assess the diagnostic accuracy of double contrast barium enema (DCBE) compared to colonoscopy among Hispanic patients with positive fecal occult blood testing (FOBT). Secondary objectives were to determine: the diagnostic accuracy according to adenoma location, size, and pathologic characteristics; and patient satisfaction with each procedure METHODS: Cross-sectional study comparing the ac curacy of DCBE and colonoscopy in detecting adenomatous polyps and/or colorectal cancer in patients with positive FOBT. DCBE and a colonoscopy were performed in all patients. Polyps identified during colonoscopy were removed and classified by histology. Tolerability and patient's satisfaction with study procedures was assessed. RESULTS: Fifty patients were enrolled, mainly men with a mean age of 63 years old. Polyps were fou in 40/50 (80%) patients in colonoscopy, compared to 19/50 (38%) in DCBE. Eighty-four percent of polyps were missed by DCBE. Sensitivity of DCBE was 45% and specificity 90% for all adenomas. Diagnostic accuracy of DCBE was 54% for any size adenomas, and 72% for >10 mm adenomas. Sensitivity increased from right to left colon while specificity decreased. Patients preferred colonoscopy over DCBE. CONCLUSIONS: This study supports the use of colo noscopy as the gold standard test for the evaluation of positive FOBT and was preferred over DCBE b the patients. Diagnostic accuracy of DCBE was inferior to colonoscopy, for all size polyps and larg adenomas. Compared to colonoscopy, DCBE is a substandard test for colorectal cancer screening and may result in ineffective outcomes.

Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis.

BACKGROUND & AIMS: Familialadenomatous polyposis (FAP) is an autosomal-dominant disorder characterized by the development of hundreds of colorectal adenomas and eventual colorectal cancer. Regression of adenomas in this syndrome occurs with the administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, but these compounds can have considerable side effects. We evaluated the efficacy of the combination of diet-derived nonprescription supplements curcumin and quercetin to regress adenomas in patients with FAP. METHODS: Five FAP patients with prior colectomy (4 with retained rectum and 1 with an ileal anal pouch) received curcumin 480 mg and quercetin 20 mg orally 3 times a day. The number and size of polyps were assessed at baseline and after therapy. The Wilcoxon signed-rank test was used to determine differences in the number and size of polyps. Treatment side effects and medication compliance also were evaluated. RESULTS: All 5 patients had a decreased polyp number and size from baseline after a mean of 6 months of treatment with curcumin and quercetin. The mean percent decrease in the number and size of polyps from baseline was 60.4% (P < .05) and 50.9% (P < .05), respectively. Minimal adverse side effects and no laboratory abnormalities were noted. CONCLUSIONS: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.

Chemoprevention of colorectal cancer.

Colorectal cancer is a major public health concern in all developed countries. Despite decades of advances in the treatment and prevention of colorectal cancer, it remains the second most common cause of cancer death. However, the optimal method for early detection remains unknown and patient compliance with screening recommendations remains poor. This has led to the development of complementary strategies, such as chemoprevention to reduce morbidity and mortality from colorectal cancer. Chemoprevention is defined as the use of specific pharmacologic or nutrient agents to prevent, reverse, or inhibit the process of carcinogenesis. This review was designed to discuss the most promising agents in colorectal chemoprevention.

Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation: a randomized placebo controlled trial.

BACKGROUND: The bioflavonoids quercetin and curcumin are renoprotective natural antioxidants. We wished to examine their effects on early graft function (EF). METHODS: Between September 2002 and August 2004, 43 dialysis dependent cadaveric kidney recipients were enrolled into a study using Oxy-Q which contains 480 mg of curcumin and 20 mg of quercetin, started after surgery and taken for 1 month. They were randomized into three groups: control (placebo), low dose (one capsule, one placebo) and high dose (two capsules). Delayed graft function (DGF) was defined as first week dialysis need and slow function (SGF) as Cr >2.5 mg/dl by day 10. Category variables were compared by chi squared and continuous variables by Kruskal-Wallis. RESULTS: There were four withdrawals: one by patient choice and three for urine leak. The control group had 2/14 patients with DGF vs. none in either treatment group. Incidence of EF was control 43%, low dose 71% and high dose 93% (P=0.013). Serum creatinine was significantly lower at 2 days (control 7.6+/-2.1, low 5.4+/-0.6, high 3.96+/-.35 P=0.0001) and 30 days (control 1.82+/-.16, low 1.65+/-.09, high 1.33 +/-.1, P=0.03). Acute rejection incidence within 6 months was control 14.3%, low dose 14.3% and high dose 0%. Tremor was detected in 13% of high dose patients vs. 46% of others. Urinary HO-1 was higher in bioflavonoid groups. CONCLUSION: Bioflavonoid therapy improved early graft function. Acute rejection and neurotoxicity were lowest in the high dose group. These bioflavonoids improve early outcomes in cadaveric renal transplantation, possibly through HO-1 induction.

Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition.

BACKGROUND & AIMS: Loss of genomic imprinting (LOI) of insulin-like growth factor II gene (IGF2) involves abnormal activation of the normally silent maternally inherited allele. LOI of IGF2 has been associated with personal and family history of colorectal neoplasia (CRN), supporting a role for LOI in colorectal carcinogenesis. Whether LOI of IGF2 is associated with known environmental risk factors for CRN is unknown. METHODS: We performed quantitative hot-stop PCR for imprinting analysis of IGF2 on normal peripheral blood lymphocytes (PBL) of individuals. Environmental exposures including tobacco, alcohol, NSAIDs, and nutrient consumption (calcium, folate, selenium, fiber, and fat) were correlated with LOI expression in PBL. Odds ratios (OR) and 95% CI were calculated. RESULTS: The prevalence of LOI of IGF2 was examined in 172 individuals. Persons with CRN (adenomas/cancer) had 5.1-fold (95% CI: 1.92-13.6) increased risk of having LOI of IGF2 in PBL compared with those without CRN. In contrast, tobacco smoking (OR = 0.96, 95% CI: 0.36-2.55), alcohol consumption (OR = 1.22, 95% CI: 0.45-3.3), and NSAIDs use (OR = 1.21, 95% CI: 0.38-3.94) were not significantly associated with LOI of IGF2. Nutrient ingestion including calcium (P = 0.61), folate (P = 0.23), selenium (P = 0.19), fiber (P = 0.63), and fat (P = 0.14) was not statistically correlated with LOI of IGF2. CONCLUSIONS: Abnormal imprinting of IGF2 gene was strongly associated with CRN but not with any of the environmental exposures examined. LOI of IGF2 does not appear to be an environmentally acquired phenomenon but rather a hereditary risk factor for CRN.