Azerbaijani
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)

Screening and Risk Factors of Colon Neoplasia

Yalnız qeydiyyatdan keçmiş istifadəçilər məqalələri tərcümə edə bilərlər
Giriş / Qeydiyyatdan keçin
Bağlantı panoya saxlanılır
Statusİşə qəbul
Sponsorlar
Case Comprehensive Cancer Center

Açar sözlər

Mücərrəd

The investigators propose a screening population-based study to systematically evaluate the accuracy and clinical relevance of sDNA testing as a potential alternative to colonoscopy screening. In addition, the investigators propose a genetic epidemiologic study of the relation between colon polyps, an established precursor of colon cancer, and two factors that may influence risk for colon cancer: candidate genes and diet.

Təsvir

Colorectal carcinoma is currently the second most common fatal cancer in the United States, and is largely preventable through the use of screening in the asymptomatic population. Although colonoscopy is considered to be the most accurate 'gold standard' screening test, there are a significant proportion of eligible patients who decline colonoscopy or in whom colonoscopy is not readily available. More recently, testing for aberrant molecular/genetic markers in stool DNA (sDNA) is emerging as a promising alternative to colonoscopy, and some professional society guidelines have endorsed the use of sDNA testing in the early detection of colorectal cancer. However, despite some guidelines that endorse sDNA testing primarily for the detection of colorectal cancer, data on the efficacy of sDNA testing for advanced adenomas, and hence prevention of colorectal cancer, are limited.

Colon carcinogenesis is a multifactorial and multistep process that involves both genetic and environmental influences. Diet clearly plays an important role. However, despite extensive research, there has been limited success in identifying such specific dietary and nutritional factors. In particular, a number of within-population studies, including several randomized trials, have yielded conflicting results and cast serious doubt on the hypothesized central role of dietary fat and fiber in colon carcinogenesis. In contrast, there is increasing evidence relating colon neoplasia to obesity, type 2 diabetes and related metabolic abnormalities. These results, together with the marked and consistent similarities in the dietary and lifestyle risk factors for type 2 diabetes and colon neoplasia have led to the notion that insulin resistance resulting from energy imbalance (excess energy intake, physical inactivity, and obesity) may be the underlying link between these two entities. Indeed, the insulin resistance-colon neoplasia hypothesis could account for many of the dietary and lifestyle risk factors of colon neoplasia and for its high incidence in Western countries. The fact that the incidences of obesity, insulin resistance syndrome, and type 2 diabetes are escalating at epidemic pace in the Western societies makes the exploration of the insulin resistance-colon neoplasia hypothesis a subject of pressing priority.

A Food Frequency Questionnaire (FFQ), a Meat Preparation Questionnaire (MPQ), and a Physical Activity Questionnaire (PAQ), all developed at the University of Arizona Cancer Center will be used to collect dietary and physical activity data.The FFQ, MPQ and PAQ questionnaires will be self-administered by each subject according to detailed written instructions, and they are mailed to the participant with the consent forms. Subjects will be asked to donate whole blood and urine samples on the day of routine colonoscopy exams. These samples will be looked at for disease markers. Stool samples will be collected to evaluate its use at detecting colon polyps using the sDNA Test and 2 FIT tests (fecal immunochemical test).

Tarixlər

Son Doğrulandı: 05/31/2020
İlk təqdim: 07/04/2012
Təxmini qeydiyyat təqdim edildi: 07/22/2012
İlk Göndərmə: 07/23/2012
Son Yeniləmə Göndərildi: 06/28/2020
Son Yeniləmə Göndərildi: 06/29/2020
Həqiqi Təhsilin Başlama Tarixi: 03/31/2012
Təxmini İlkin Tamamlanma Tarixi: 12/31/2020
Təxmini İşin Tamamlanma Tarixi: 12/31/2020

Vəziyyət və ya xəstəlik

Colon Cancer

Müdaxilə / müalicə

Other: Stool DNA Test

Procedure: biopsies of rectal and colon mucosa

Other: Questionnaires

Faza

-

Qol Qrupları

QolMüdaxilə / müalicə
Individuals without colon polyps
Individuals with colon polyps

Uyğunluq Kriteriyaları

Təhsil üçün uyğun yaşlar 30 Years Üçün 30 Years
Təhsilə Uyğun CinslərAll
Nümunə götürmə metoduProbability Sample
Sağlam Könüllüləri qəbul edirBəli
Kriteriyalar

Inclusion Criteria:

- patients undergoing routine colonoscopy at University Hospitals, Cleveland Ohio

Exclusion Criteria:

- Unable to give written consents

- Unable to fill the questionnaires

- A history of polyps within the past 10 years (except hyperplastic polyps)

- Family history of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

- Personal history of inflammatory bowel disease

- Personal diagnosis of any cancer, with the exception of non-melanoma skin cancer

- Any major colon surgeries (e.g. resectioning)

Nəticə

İlkin nəticə tədbirləri

1. Stool DNA (sDNA) Feasibility and Compliance [within 12 weeks prior to the colonoscopy]

For this aim, we will recruit a sub-sample of the study participants to perform the sDNA test for aberrantly methylated markers in addition to their colonoscopy to assess willingness to participate, compliance with test protocol and patient satisfaction to determine potential for a larger study to evaluate the effectiveness of this test for detection of colon adenomas.

2. Efficacy of sDNA testing for the detection of advanced adenomas [prior to the colonoscopy]

For the sDNA test aims, the primary goals are to assess the sensitivity and specificity of sDNA testing for the detection of advanced adenomas, and to compare the performance of the Exact sDNA Panel with that of FIT. The sensitivity and specificity of sDNA and FIT will be estimated based on the concordance and discordance of advanced adenomas detected against that of colonoscopy as the gold standard

İkincili Nəticə Tədbirləri

1. Concordance/discordance between tissue and stool DNA aberrant methylation markers [Stool sample within 2 weeks of colonoscopy]

Biopsies of rectal and colon mucosa collected at the beginning of the colonoscopy for analysis of 15-PGDH pathway factors [levels of prostaglandin E2 (PG E2), and mRNA for 15-PGDH, COX-1 and COX-2 expression] as markers of risk of developing adenoma.

2. Persistence of positive sDNA testing after removal of advanced adenomas [at 12 months after initial colonoscopy]

For this aim we will follow-up participants who have had positive sDNA tests and at least one advanced adenoma removed during colonoscopy. At 12 months after their initial sDNA test and colonoscopy, we will ask them to repeat the sDNA test in addition to colonoscopy recommended by their physician as standard of care.

3. Assess the frequency of missed or occult colonic and upper gastrointestinal neoplasia in patients with initially normal colonoscopies and persistently positive sDNA testing. [at 12 months after initial colonoscopy]

For this aim we will follow-up participants who have had positive sDNA tests and negative colonoscopy (i.e., no adenomatous polyps observed at initial colonoscopy). At 12 months after their initial sDNA test and colonoscopy, we will ask them to repeat the sDNA test. If this second sDNA test is also positive, the participant will be offered the opportunity to have both a colonoscopy and an upper GI endoscopy (also called esophagogastroduodenoscopy or EGD)

4. Insulin Resistance Syndrome [at the time of the colonoscopy]

Use latent structural equation models to fully incorporate information on the overall relations among insulin resistance syndrome pathway factors and colon polyps, including both direct and indirect effects as well as interactions between these factors.

5. Analyses stratified by ethnicity (Caucasians versus African Americans), and gender. [at the time of the colonoscopy]

The analysis by ethnicity is of particular interest in sDNA testing as there is evidence that large right-sided adenomas are more prevalent among African Americans, and this ethnic population is less likely to receive screening colonoscopy as compared to Caucasians. Furthermore, the ability of sDNA and FIT for the detection of nonadvanced adenomas will be evaluated. These lesions will be defined as adenomas that are less than 1 cm in diameter and without evidence of high grade dysplasia.

6. Examine the impact of candidate gene variants in the insulin-GH-IGF-IRS axis on colon polyps. [at the time of the colonoscopy]

Evaluate whether each of the following candidate gene polymorphisms and their haplotypes are linked to colon polyps: 1) Insulin; 2) Growth Hormone; 3) IGF-1; and 4) IRS-1.

7. Evaluate the association of dietary patterns, glycemic index (GI) and glycemic load (GL) with colon polyps. [at 12 months]

Conceptually, dietary patterns represent a broader picture of human diet, and thus may be more predictive of disease risk than individual foods or nutrients. In addition, there is growing evidence relating GI and/or GL to risks of obesity, type 2 diabetes as well as colon neoplasia. Therefore, we hypothesize that high dietary GL and/or GI, and/or a Western dietary pattern defined by a diverse array of dietary factors are associated with increased risk of colon polyps.

8. Synthesize the information on candidate genes and diet by looking at their joint effects on colon polyps [at the time of the colonoscopy]

1) investigate their potential joint actions [i.e., gene-diet and gene-gene]; 2) use a latent structural equation modeling approach to comprehensively evaluate these factors' potential direct as well as indirect (mediated by insulin resistance syndrome) impact, on colon polyps.

9. To investigate the association of activated (phosphorylated) IRS1, AKT and mTOR with colon adenomas. [at the time of the colonoscopy]

We will compare the immunohistochemistry of phosphorylated IRS1, AKT and mTOR in colon adenoma tissues with that in colon tissues from healthy control patients. Investigate the effect of obesity on the activation of the IRS1, AKT and mTOR by stratifying our cases and controls into lean and obese individuals. Evaluate the effects of serum levels of insulin, glucose, and insulin resistance index (HOMA-IR) on the activation of the IRS1, AKT and mTOR in colonic tissue.

Facebook səhifəmizə qoşulun

Elm tərəfindən dəstəklənən ən tam dərman bitkiləri bazası

  • 55 dildə işləyir
  • Elm tərəfindən dəstəklənən bitki mənşəli müalicələr
  • Təsvirə görə otların tanınması
  • İnteraktiv GPS xəritəsi - yerdəki otları etiketləyin (tezliklə)
  • Axtarışınızla əlaqəli elmi nəşrləri oxuyun
  • Təsirlərinə görə dərman bitkilərini axtarın
  • Maraqlarınızı təşkil edin və xəbər araşdırmaları, klinik sınaqlar və patentlər barədə məlumatlı olun

Bir simptom və ya bir xəstəlik yazın və kömək edə biləcək otlar haqqında oxuyun, bir ot yazın və istifadə olunan xəstəliklərə və simptomlara baxın.
* Bütün məlumatlar dərc olunmuş elmi araşdırmalara əsaslanır

Google Play badgeApp Store badge