105 research outputs found
Factors associated with late stage at diagnosis among Puerto Ricoâs government health plan colorectal cancer patients: a cross-sectional study
Report of a Novel Mutation in MLH1
In Puerto Rico, colorectal cancer (CRC) represents the second leading cause of cancer in men and women. Familial CRC accounts for 10â15% of the total CRC cases, while Lynch syndrome accounts for approximately 2â4% 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
Correlates of Colorectal Cancer Screening among Hispanics: Results from the 2008 Puerto Rico Behavioral Risk Factor Surveillance System Survey
IntroductionâColorectal cancer (CRC) is the second most commonly diagnosed cancer in
Puerto Rico (PR). Given the lack of information on cancer screening behavior, we identified
factors associated with CRC screening among adults aged â„ 50 years in PR.
MethodsâAge eligible adults who participated in the PR- Behavioral Risk Factor Surveillance
System (BRFSS) in 2008 were included in the analysis (n=2,920). Weighted prevalence of fecal
occult blood test (FOBT) within two years and of Sigmoidoscopy/Colonoscopy examination
within five years before the interview were estimated and logistic regression models were used to
assess factors associated with these CRC screening practices.
ResultsâOverall 8.2% (95% CI 7.1%-9.3%) of the participants had had the FOBT within the
past two years, 39.8% (95% CI 37.7%-41.9%) had sigmoidoscopy/colonoscopy examination
within 5 years and 46.7% (95% CI= 44.5%-48.8%) had ever had any type of CRC screening.
Factors positively associated to CRC screening in multivariate analyses included older age, higher
education, and having had a routine check-up in the past year. Gender, body mass index, and other
relevant covariates evaluated were not associated to screening behavior.
ConclusionsâPrevalence of CRC screening in PR during 2008 was below the goals established
by Healthy People 2010 (50.0%) and 2020 (70.5%). We provide the first population-based
estimates of CRC screening prevalence and correlates in a US predominantly Hispanic population.
Low adherence to CRC screening may result in late stage at diagnosis and poorer disease
outcomes. Public health efforts should focus on the promotion of CRC screening and early
detection
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; PÂ =Â .27), advanced adenomas (7.7% vs 8.2%; PÂ =Â .73) or clinically significant serrated polyps (10.0% vs 10.3%; PÂ = .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
Cancer health disparities in racial/ethnic minorities in the United States
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 USAâAfrican 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.Fil: Zavala, Valentina A.. University of California; Estados UnidosFil: Bracci, Paige M.. University of California; Estados UnidosFil: Carethers, John M.. University of Michigan; Estados UnidosFil: Carvajal Carmona, Luis. University of California at Davis; Estados UnidosFil: Coggins, Nicole B.. University of California at Davis; Estados UnidosFil: Cruz Correa, Marcia R.. Universidad de Puerto Rico; Puerto RicoFil: Davis, Melissa. No especifĂca;Fil: de Smith, Adam J.. University of California; Estados UnidosFil: Dutil, Julie. Ponce Research Institute; Puerto RicoFil: Figueiredo, Jane C.. Cedars Sinai Medical Center; Estados UnidosFil: Fox, Rena. University of California; Estados UnidosFil: Graves, Kristi D.. University Of Georgetown; Estados UnidosFil: Gomez, Scarlett Lin. University of California; Estados UnidosFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Neuhausen, Susan L.. No especifĂca;Fil: Newman, Lisa. No especifĂca;Fil: Nguyen, Tung. University of California; Estados UnidosFil: Palmer, Julie R.. National Institutes of Health; Estados UnidosFil: Palmer, Nynikka R.. University of California; Estados UnidosFil: PĂ©rez Stable, Eliseo J.. National Institutes of Health; Estados UnidosFil: Piawah, Sorbarikor. University of California; Estados UnidosFil: Rodriquez, Erik J.. National Institutes of Health; Estados UnidosFil: Sanabria Salas, MarĂa Carolina. Instituto Nacional de CancerologĂa; ColombiaFil: Schmit, Stephanie L.. University of Southern California; Estados UnidosFil: Serrano Gomez, Silvia J.. Instituto Nacional de CancerologĂa; ColombiaFil: Stern, Mariana Carla. University of Southern California; Estados UnidosFil: Weitzel, Jeffrey. No especifĂca;Fil: Yang, Jun J.. St. Jude Childrenâs Research Hospital; Estados UnidosFil: Zabaleta, Jovanny. No especifĂca;Fil: Ziv, Elad. University of California; Estados UnidosFil: Fejerman, Laura. University of California; Estados Unido
A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas
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
Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
In the version of this article initially published, the author affiliations incorrectly listed âCandiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italyâ as âCandiolo Cancer Institute, Candiolo, Italy.â The change has been made to the HTML and PDF versions of the article
Novel Common Genetic Susceptibility Loci for Colorectal Cancer
BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5âĂâ10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5âĂâ10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5âĂâ10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screenin
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