Browsing by Subject "Colorectal Cancer"

Now showing 1 - 6 of 6
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    Colorectal Cancer Screening in the US: The Impact of Oversurveillance, Physician Supply and Coverage Mandates
    (2015-10) Abban, Bartholomew
    Screening for precursor adenomatous polyps has been proven to be effective in reducing colorectal cancer mortality risk. Although most screening guidelines do not recommend any one of the several screening tests for CRC over the others, colonoscopy increasingly is being adopted as the primary test for screening. In addition, colonoscopy is recommended for post-polypectomy and post-colectomy surveillance of colorectal cancer. Despite the considerable evidence supporting the effectiveness of screening for CRC, its uptake has lagged considerably behind that of breast cancer screening. Over the past twenty years, the Department of Health and Human Services (DHHS), the Centers for Disease Control and Prevention (CDC) and many national, state and local organizations have embarked on several programs and campaigns in a bid to raise awareness about colorectal cancer and increase screening uptake. At the same time, there is a growing concern that the current physician supply is inadequate to support a broader colonoscopy-based screening and surveillance. This research examines these concerns from three fronts. First, we use a population-based state-transition Markov model of the natural history of colorectal cancer, applied to census data and prevailing screening guidelines, to forecast the demand for colonoscopy and examine the impact of premature post-polypectomy CRC surveillance on the annual volume of colonoscopies. Second, we combine the Behavioral Risk Factor Surveillance System (BRFSS) survey with physician resource data to examine the conditional effect of county-level physician supply on screening participation. Third, we use longitudinal BRFSS survey data to estimate the effect of the policy of state-mandated colorectal cancer screening benefit by health insurers on the probability of an insured individual undergoing screening.
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    Investigating The Role Of Cystic Fibrosis Transmembrane Conductance Regulator On Oxidative Stress In Colorectal Cancer
    (2020-05) Singhania, Mekhla
    Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women in the United States, with an estimated 53,200 deaths in 2020 (Siegel, Miller, & Jemal, 2020). Our lab identified Cystic Fibrosis Transmembrane Regulator (CFTR) as a CRC tumor suppressor gene in mice and humans. However, the mechanism by which CFTR acts as a tumor suppressor gene in CRC is unknown. To identify potential pathways, we compared gene expression in CFTR-low expressing CRC vs. CFTR high expressing tumors in several publicly available databases using gene set enrichment analysis. These analyses revealed that a common subset of genes is responsive in CFTR-low expressing tumors and in HIF1α-high tumors. HIF1α protein is induced by oxidative stress and is known to play a protective role in the oxidative stress pathway. To investigate the significance of this correlation, I hypothesized that downregulation of CFTR protects against oxidative stress. To test this hypothesis, I compared cell viability in human Caco-2 CRC cell lines: one in which CFTR has been knocked out by CRISPR-Cas9 modification (CFTR-KO) vs. matched parental controls (CFTR-WT). Each cell line was treated with menadione to induce oxidative stress. When cell viability was measured using an MTT assay, a trend was observed, where CFTR-KO cells were less affected by menadione than CFTR-WT. This suggests that CFTR deficiency may help colon cancer cells to survive better in an oxidative stress environment. To determine if CFTR deficiency promotes this survival of CRC cells by change in ROS levels, ROS detection assays were carried out to compare ROS levels between CFTR WT and CFTR KO cell lines. We observed a trend where CFTR-WT cells had higher ROS levels than CFTR-KO in this oxidative stress environment. This suggests that CFTR deficiency maybe promoting survival of CRC cells in an oxidative stress environment by reducing ROS levels. This work will help to better understand the role of CFTR as a tumor suppressor gene in CRC.
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    Personalizing Colorectal Cancer Care: Opportunities for Pharmacogenomics
    (2021-09) Rivers, Zachary
    A diagnosis of metastatic colorectal cancer impacts nearly 30,000 Americans a year, and while treatments are available, they come with the risk of morbidity and mortality. Personalized medicine, the use of an individual’s genetic information to tailor their treatment, is used in oncology to determine somatic, druggable targets to select therapy. It also provides an opportunity to understand the likelihood that an individual would develop toxicities during treatment or fail to respond to treatment. This approach has not been integrated into clinical practice at the same level as the targeted approach. This dissertation explores the opportunities for germline pharmacogenetic testing to inform chemotherapy and non-chemotherapy medication selection in a historical cohort of Americans with metastatic colorectal cancer and models the theoretical cost-effectiveness of implementing this approach.
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    Regulation of KCNQ1 and CFTR in Colorectal Cancer
    (2019-05) Madden, Rebecca
    Colorectal cancer is the 2nd deadliest cancer in the US with more than 50,000 deaths in 2017. Our group has identified KCNQ1 and CFTR as colorectal cancer tumor suppressors. KCNQ1-low as well as CFTR-low expressing tumors have significantly poorer prognosis than high expressers: KCNQ1-low in stages II, III and IV colorectal cancer; CFTR-low in stage II. Thus, it is important to understand how KCNQ1 and CFTR are downregulated in these poor prognosis cancers. KCNQ1 and CFTR are expressed at the base of the intestinal crypt, the site of the stem cell compartment and origin of colorectal cancer. The Wnt/ β-catenin signaling pathway is important in determining stemness and is dysregulated in >85% of human colon cancers. Therefore, I am testing two hypotheses involving Wnt/ β-catenin and these tumors suppressors: 1) KCNQ1 is regulated through a putative enhancer region containing a β-catenin binding site and 2) KCNQ1 and CFTR regulate β-catenin activity. Our putative enhancer region was identified through a survey of the KCNQ1 genomic sequence for eQTLs (SNPs associated with altered expression of KCNQ1) which identified SNP rs2283155 in KCNQ1 intron 2. SNPs are markers for potential polymorphic variants associated with altered gene expression. The enhancer region includes the SNP rs2283155, a TCF7L2 binding site (the binding partner of transcriptionally active β-catenin) and a larger DNase I hypersensitivity enhancer region. Luciferase reporter assays showed regulation by our enhancer region of a reporter gene. Follow-up data has suggested that KCNQ1 is the gene being regulated. Second, to investigate the effect of Kcnq1 and Cftr on β-catenin signaling, I am examining β-catenin in organoids, a well-established model of the stem cell compartment. Activation of β-catenin is characterized by its movement from the cytoplasm or membrane to the nucleus. I developed an immunofluorescence assay to quantitatively measure nuclear β-catenin localization in Kcnq1 deficient/expressing and Cftr deficient/expressing organoids. These organoids had increased β-catenin activity in Kcnq1-deficient and Cftr-deficient organoids, suggesting a mechanism for tumor suppressor activity of Kcnq1 and Cftr. This work may provide insight into the role of Kcnq1 and Cftr within the cellular environment and potential ways to manipulate their expression to improve survival.
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    Screening Colonoscopy is Safe and Effective in Elderly Adults
    (2008-11-24) Jaques, Cory D
    Colonoscopy is an effective tool for screening for colorectal cancer in adults over 75, and the rates of complications are similar to those for people under 65. In general, colonoscopy is recommended in adults with a life expectancy of five years or more. Studies have found that screening colonoscopy in the very elderly (over 80) results in only 15% of the expected gain in life expectancy in younger patients, and in this population should only be performed with careful consideration to risks and benefits for that particular patient. Expert recommendation is to evaluate life expectancy, and only screen those with 5 or more years of life expectancy.
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    Screening for Colorectal Cancer: Colonoscopy vs. Sigmoidoscopy plus Fecal Blood Tests
    (2009-09-18) Allen, William
    Colorectal cancer screening has many different modalities. Two of the most effective modalities are sigmoidoscopy combined with fecal occult blood tests and colonoscopy. This article will explain these tests and their benefits.