SNPMiner Trials by Shray Alag


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Report for SNP rs174535

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 Fatty Acid Desaturase Activity, Fish Oil and Colorectal Cancer Prevention

Colorectal cancer is the second leading cause of cancer-related death within the United States. Animal models and observational studies have suggested that marine-derived n-3 polyunsaturated fatty acids [PUFA] such as eicosapentanoic acid [EPA] and docosahexanoic acid [DHA] may reduce the risk of colorectal cancer. In addition, it may be the relative proportion of n-3 to n-6 PUFAs that best determines the chemopreventive effects of fish oils. This ratio is important because the n-6 PUFA, arachidonic acid (ARA), is converted via the cyclo-oxygenase (COX) pathway to prostaglandin E2 (PGE2), an inflammatory eicosanoid overproduced in colorectal neoplasms while EPA is converted to the anti-inflammatory prostaglandin E3 (PGE3). While the ratio of n-6 to n-3 PUFAs can be altered through dietary changes, genetic factors may also influence this ratio. Recent genetic studies have demonstrated that much of the tissue levels of ARA is determined by differences in a gene called fatty acid desaturase 1 (FADS1). FADS1 is the rate-limiting enzyme in the conversion of linoleic acid, the most commonly consumed PUFA in the Western diet, to ARA, and one particular genetic variant caller rs174537 is associated with lower fatty acid desaturase activity and subsequently lower tissue levels of ARA. The study hypothesis is that individuals with genetically determined lower activity of FADS1 will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity because of lower tissue levels of ARA and subsequently a more favorable n-6 to n-3 PUFA ratio. To test this hypothesis the investigators will recruit 150 participants with recently identified adenomatous polyps and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. The first factor will be FADS1 genotype (GG, GT, and TT) and the second factor will be fish oil supplementation (fish oil versus placebo). The primary outcome will be the change in rectal epithelial cell growth and cell death. Secondary outcomes will include rectal epithelial cell expression of genes important in PGE2 production, rectal cell production of PGE2 and PGE3, rectal mucosal tissue levels of fatty acids, and changes in biomarkers of inflammation (C-reactive protein), adipokines (leptin, adiponectin), and markers of insulin sensitivity. The specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention. The investigators long-term objectives are to determine genetic factors that might influence the efficacy of fish oil supplementation in order to conduct a more definitive adenoma recurrence trial using marine-derived n-3 PUFAs. The investigators anticipate that fish oil will have anti-neoplastic effect and individuals with low FADS1 activity will have a greater response compared to individuals with high FADS1 activity

NCT01661764 Co Colorectal Adenomatous Polyps Drug: Eicosapentanoic acid and docosahexanoic acid Drug: Oleic Acid
MeSH: Adenomatous Polyps

Inclusion Criteria: - ≥ 40 and < 80 years of age - History of 1 or more adenomatous polyps - Consent to be contacted for future studies - Participants with known genotype for rs174535 in FADS1 - Prior participation in the Tennessee Colorectal Polyp Study or the Personalized Prevention of Colorectal Cancer Trial Exclusion Criteria: - Previously resected colorectal cancer - Coronary artery disease or congestive heart failure - Current metabolic or life-threatening disease - Currently taking fish oil supplements - Inability or unwillingness to stop NSAIDs or ASA during the study - Allergic to fish products - Diagnosis of inflammatory bowel disease - Diagnosis of any cancer (except non-melanoma skin cancer) - Diagnosis of liver or kidney disease - Pregnant or breast feeding Inclusion Criteria: - ≥ 40 and < 80 years of age - History of 1 or more adenomatous polyps - Consent to be contacted for future studies - Participants with known genotype for rs174535 in FADS1 - Prior participation in the Tennessee Colorectal Polyp Study or the Personalized Prevention of Colorectal Cancer Trial Exclusion Criteria: - Previously resected colorectal cancer - Coronary artery disease or congestive heart failure - Current metabolic or life-threatening disease - Currently taking fish oil supplements - Inability or unwillingness to stop NSAIDs or ASA during the study - Allergic to fish products - Diagnosis of inflammatory bowel disease - Diagnosis of any cancer (except non-melanoma skin cancer) - Diagnosis of liver or kidney disease - Pregnant or breast feeding Co Colorectal Adenomatous Polyps Adenomatous Polyps 1.Rationale and Specific Aims Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer related mortality in the United States.

At the baseline visit, the investigators will re-genotype rs174535 to confirm the accuracy of the imputation process.

Primary Outcomes

Description: The primary outcome of interest is rectal epithelial cell proliferation, as measured by Ki67 (mib-1) labeling. Expression of Ki-67 in colon epithelial cells will be detected following the standard IHC protocol of EnVision™+ System, HRP (DAKO).

Measure: Rectal Epithelial Cell Proliferation

Time: 6 month

Description: The primary outcome of interest is rectal epithelial cell apoptosis as measured by TUNEL (TdT-mediated dUTP Nick-End Labeling). The TUNEL assay is conducted to measure apoptosis of colon epithelium using DeadEnd Colorimetric TUNEL System (Promega). After all fields of each sample are measured, the final immunoreaction indices are generated automatically by setting algorithms as ''total positive area / total nuclear area. Apoptotic activity is also scored using standard morphologic criteria applied to H&E stained sections.

Measure: Rectal Epithelial Cell Apoptosis

Time: 6 months

Secondary Outcomes

Description: Expression of COX-2 in rectal epithelial cells will be detected following the standard IHC protocol of EnVision™+ System, HRP (DAKO).

Measure: Rectal Epithelial Cell COX-2 Expression

Time: 6 months

Description: Expression of 15-PGDH in rectal epithelial cells will be detected following the standard IHC protocol of EnVision™+ System, HRP (DAKO).

Measure: Rectal Epithelial Cell 15-PGDH Expression

Time: 6 months

Description: Lipids will be extracted using the method of Folch-Lees

Measure: Rectal Epithelial Cell Phospholipid Fatty Acid Content

Time: 6 months

Description: liquid chromatography/tandem mass spectrometric on rectal biopsy samples

Measure: Rectal Epithelial Cell Production of PGE2 and PGE3

Time: 6 months

Other Outcomes

Measure: C-reactive Protein

Time: 6 months

Description: leptin and adiponectin

Measure: Adipokines

Time: 6 months

Description: homeostasis model assessment-insulin resistance (HOMA-IR) HOMA-IR. Fasting insulin and glucose were be used to determine HOMA-IR: [fasting glucose (mmol/l) x fasting insulin (µU/ml)]/22.5]", Optimal insulin sensitivity: < 1, Early insulin resistance: > 1.9, Significant insulin resistance: > 2.9

Measure: Insulin Sensitivity

Time: 6 months


HPO Nodes