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Case-control study of candidate gene methylation and adenomatous polyp formation.

ABSTRACT: PURPOSE:Colorectal cancer (CRC) is one of the most common and preventable forms of cancer but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70-90 % of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation. METHODS:Patients recruited from a local endoscopy clinic provided informed consent and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors. Cases were individuals with a histopathologically confirmed adenoma, and controls included patients with a normal colonoscopy or those with histopathological findings not requiring heightened surveillance (normal biopsy, hyperplastic polyp). Methylation-specific polymerase chain reaction was used to characterize candidate gene promoter methylation. Odds ratios (ORs) and 95 % confidence intervals (95% CIs) were calculated using unconditional multivariable logistic regression to test the hypothesis that candidate gene methylation differed between cases and controls, after adjustment for confounders. RESULTS:Complete data were available for 107 participants; 36 % had adenomas (men 40 %, women 31 %). Hypomethylation of the MINT1 locus (OR 5.3, 95% CI 1.0-28.2) and the PER1 (OR 2.9, 95% CI 1.1-7.7) and PER3 (OR 11.6, 95% CI 1.6-78.5) clock gene promoters was more common among adenoma cases. While specificity was moderate to high for the three markers (71-97 %), sensitivity was relatively low (18-45 %). CONCLUSION:Follow-up of these epigenetic markers is suggested to further evaluate their utility for adenoma screening or surveillance.

SUBMITTER: Alexander M

PROVIDER: S-EPMC5288296 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Case-control study of candidate gene methylation and adenomatous polyp formation.

Alexander M M Burch J B JB Steck S E SE Chen C-F CF Hurley T G TG Cavicchia P P Shivappa N N Guess J J Zhang H H Youngstedt S D SD Creek K E KE Lloyd S S Jones K K Hébert J R JR

International journal of colorectal disease 20161022 2

<h4>Purpose</h4>Colorectal cancer (CRC) is one of the most common and preventable forms of cancer but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70-90 % of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation.<h4>Methods ...[more]

PMID: 27771773

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Project description:Preeclampsia is a hypertensive, multi-system pregnancy disorder whose pathophysiology remains unclear. Elevations in circulating soluble endoglin (sENG) and placental/blood ENG mRNA expression antedate the clinical onset of preeclampsia. This study investigated if endoglin (ENG) pathway genetic variation was also associated with the development of preeclampsia.We used a case-control candidate gene association design. Data from 355 white (181 preeclampsia cases/174 controls) and 60 black (30 preeclampsia cases/30 controls) women matched on ancestry, age, and parity were analyzed. Tagging single nucleotide polymorphisms (tSNPs) and potentially functional SNPs in ENG, TGF?1, TGF?R1, ALK1, and TGF?R2 were genotyped with iPLEX® and TaqMan®. Chi-square or Fisher's exact tests were used to conduct allele/genotype/haplotype tests in white/black subgroups separately. Odds ratios were computed with binary logistic regression for tSNPs with significant genotype tests.Of the 49 SNPs evaluated, variation in two ENG tSNPs (rs11792480, rs10121110) and one TGF?R2 tSNP (rs6550005) was associated with preeclampsia in white women (P <0.05, each). In black women, variation in two TGF?1 tSNPs (rs4803455, rs4803457), one TGF?R1 tSNP (rs10739778), and three TGF?R2 tSNPs (rs6550005, rs1346907, rs877572) was associated with preeclampsia (P <0.05, each). Further evaluation of ENG tSNP rs10121110 revealed that white women inheriting the AA genotype were 2.29 times more likely to develop preeclampsia compared to the GG genotype (P?=?0.008, [99% CI: 1.02 to 5.13]). For black women, similar evaluation of TGF?1 tSNP rs4803457 revealed women inheriting the CT genotype were 7.44 times more likely to develop preeclampsia than those with the CC genotype (P?=?0.005, [99% CI: 1.19 to 46.41]).ENG pathway genetic variation is associated with preeclampsia. Different ENG pathway genes may be involved in preeclampsia development among white and black women. Additional studies are needed to validate these findings and to determine if genetic variation in ENG pathway genes impacts ENG and sENG levels in preeclampsia.

Dataset Information

Case-control study of candidate gene methylation and adenomatous polyp formation.

Publications

Case-control study of candidate gene methylation and adenomatous polyp formation.

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