Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29

    Article  PubMed  Google Scholar 

  2. Cancer screening-United States 2010 (2012) MMWR Morb Mortal Wkly Rep 61(3):41–45

    Google Scholar 

  3. Semrad TJ, Tancredi DJ, Baldwin LM, Green P, Fenton JJ (2011) Geographic variation of racial/ethnic disparities in colorectal cancer testing among medicare enrollees. Cancer 117(8):1755–1763

    Article  PubMed  PubMed Central  Google Scholar 

  4. Klabunde CN, Schenck AP, Davis WW (2006) Barriers to colorectal cancer screening among medicare consumers. Am J Prev Med 30(4):313–319

    Article  PubMed  Google Scholar 

  5. Halbert CH, Barg FK, Guerra CE et al (2011) Cultural, economic, and psychological predictors of colonoscopy in a national sample. J Gen Intern Med 26(11):1311–1316

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nelson DE, Bolen J, Marcus S, Wells HE, Meissner H (2003) Cancer screening estimates for U.S. metropolitan areas. Am J Prev Med 24:301–309

    Article  PubMed  Google Scholar 

  7. Baker DW, Brown T, Buchanan DR et al (2014) Comparative effectiveness of a multifaceted intervention to improve adherence to annual colorectal cancer screening in community health centers: a randomized clinical trial. JAMA Intern Med 174(8):1235–1241

    Article  PubMed  Google Scholar 

  8. Ahn SB, Han DS, Bae JH, Byun TJ, Kim JP, Eun CS (2012) The miss rate for colorectal adenoma determined by quality-adjusted, back-to-back colonoscopies. Gut and liver 6(1):64–70

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hassan C, Giorgi Rossi P, Camilloni L et al (2012) Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther 36(10):929–940

    Article  CAS  PubMed  Google Scholar 

  10. Morikawa T, Kato J, Yamaji Y et al (2007) Sensitivity of immunochemical fecal occult blood test to small colorectal adenomas. Am J Gastroenterol 102(10):2259–2264

    Article  PubMed  Google Scholar 

  11. Wong CK, Fedorak RN, Prosser CI, Stewart ME, van Zanten SV, Sadowski DC (2012) The sensitivity and specificity of guaiac and immunochemical fecal occult blood tests for the detection of advanced colonic adenomas and cancer. Int J Color Dis 27(12):1657–1664

    Article  Google Scholar 

  12. Yang H, Xia BQ, Jiang B et al (2013) Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis. Can J Gastroenterol 27(8):467–475

    Article  PubMed  PubMed Central  Google Scholar 

  13. Jones RM, Woolf SH, Cunningham TD et al (2010) The relative importance of patient-reported barriers to colorectal cancer screening. Am J Prev Med 38(5):499–507

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ganepola GA, Nizin J, Rutledge JR, Chang DH (2014) Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer. World J Gastrointest Oncol 6(4):83–97

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hong L, Ahuja N (2013) DNA methylation biomarkers of stool and blood for early detection of colon cancer. Genet Test Mol Biomarkers 17(5):401–406

    Article  CAS  PubMed  Google Scholar 

  16. Jasperson KW, Tuohy TM, Neklason DW, Burt RW (2010) Hereditary and familial colon cancer. Gastroenterology 138(6):2044–2058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hsu MC, Huang CC, Choo KB, Huang CJ (2007) Uncoupling of promoter methylation and expression of Period1 in cervical cancer cells. Biochem Biophys Res Commun 360(1):257–262

    Article  CAS  PubMed  Google Scholar 

  18. Lao VV, Grady WM (2011) Epigenetics and colorectal cancer. Nat Rev Gastroenterol Hepatol 8(12):686–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP (1999) CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 96(15):8681–8686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. O'Brien MJ, Yang S, Mack C et al (2006) Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points. Am J Surg Pathol 30(12):1491–1501

    Article  PubMed  Google Scholar 

  21. Rashid A, Shen L, Morris JS, Issa JP, Hamilton SR (2001) CpG island methylation in colorectal adenomas. Am J Pathol 159(3):1129–1135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Conteduca V, Sansonno D, Russi S, Dammacco F (2013) Precancerous colorectal lesions (review). Int J Oncol 43(4):973–984

    CAS  PubMed  Google Scholar 

  23. Wynter CV, Kambara T, Walsh MD, Leggett BA, Young J, Jass JR (2006) DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients. Int J Cancer 118(4):907–915

    Article  CAS  PubMed  Google Scholar 

  24. Garrity-Park MM, Loftus EV Jr, Sandborn WJ, Bryant SC, Smyrk TC (2010) Methylation status of genes in non-neoplastic mucosa from patients with ulcerative colitis-associated colorectal cancer. Am J Gastroenterol 105(7):1610–1619

    Article  CAS  PubMed  Google Scholar 

  25. Kim JC, Choi JS, Roh SA, Cho DH, Kim TW, Kim YS (2010) Promoter methylation of specific genes is associated with the phenotype and progression of colorectal adenocarcinomas. Ann Surg Oncol 17(7):1767–1776

    Article  PubMed  Google Scholar 

  26. Pufulete M, Al-Ghnaniem R, Leather AJ et al (2003) Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study. Gastroenterology 124(5):1240–1248

    Article  CAS  PubMed  Google Scholar 

  27. Lim U, Flood A, Choi SW et al (2008) Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women. Gastroenterology 134(1):47–55

    Article  PubMed  Google Scholar 

  28. King WD, Ashbury JE, Taylor SA et al (2014) A cross-sectional study of global DNA methylation and risk of colorectal adenoma. BMC Cancer 14:488

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cravo M, Fidalgo P, Pereira AD et al (1994) DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prev 3(6):473–479

    Article  CAS  PubMed  Google Scholar 

  30. Ally MS, Al-Ghnaniem R, Pufulete M (2009) The relationship between gene-specific DNA methylation in leukocytes and normal colorectal mucosa in subjects with and without colorectal tumors. Cancer Epidemiol Biomark Prev 18(3):922–928

    Article  CAS  Google Scholar 

  31. Gao Y, Killian K, Zhang H et al (2012) Leukocyte DNA methylation and colorectal cancer among male smokers. World J Gastrointest Oncol 4(8):193–201

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kaaks R, Stattin P, Villar S et al (2009) Insulin-like growth factor-II methylation status in lymphocyte DNA and colon cancer risk in the Northern Sweden Health and Disease cohort. Cancer Res 69(13):5400–5405

    Article  CAS  PubMed  Google Scholar 

  33. Mitchell SM, Ross JP, Drew HR et al (2014) A panel of genes methylated with high frequency in colorectal cancer. BMC Cancer 14:54

    Article  PubMed  PubMed Central  Google Scholar 

  34. Cui H, Cruz-Correa M, Giardiello FM et al (2003) Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299(5613):1753–1755

    Article  CAS  PubMed  Google Scholar 

  35. McKay JA, Xie L, Harris S, Wong YK, Ford D, Mathers JC (2011) Blood as a surrogate marker for tissue-specific DNA methylation and changes due to folate depletion in post-partum female mice. Mol Nutr Food Res 55(7):1026–1035

    Article  CAS  PubMed  Google Scholar 

  36. Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM (2011) DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics 6(7):828–837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Binefa G, Rodriguez-Moranta F, Teule A, Medina-Hayas M (2014) Colorectal cancer: from prevention to personalized medicine. World J Gastroenterol 20(22):6786–6808

    Article  PubMed  PubMed Central  Google Scholar 

  38. Coppede F, Lopomo A, Spisni R, Migliore L (2014) Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J Gastroenterol 20(4):943–956

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sakai E, Nakajima A, Kaneda A (2014) Accumulation of aberrant DNA methylation during colorectal cancer development. World J Gastroenterol 20(4):978–987

    Article  PubMed  PubMed Central  Google Scholar 

  40. Jacobs ET, Van Pelt C, Forster RE et al (2013) CYP24A1 and CYP27B1 polymorphisms modulate vitamin D metabolism in colon cancer cells. Cancer Res 73(8):2563–2573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shen R, Tao L, Xu Y, Chang S, Van Brocklyn J, Gao JX (2009) Reversibility of aberrant global DNA and estrogen receptor-alpha gene methylation distinguishes colorectal precancer from cancer. Int J Clin Exp Pathol 2(1):21–33

    PubMed  Google Scholar 

  42. Mazzoccoli G, Panza A, Valvano MR et al (2011) Clock gene expression levels and relationship with clinical and pathological features in colorectal cancer patients. Chronobiol Int 28(10):841–851

    Article  CAS  PubMed  Google Scholar 

  43. Silva TD, Vidigal VM, Felipe AV et al (2013) DNA methylation as an epigenetic biomarker in colorectal cancer. Oncol Lett 6(6):1687–1692

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Haus EL, Smolensky MH (2013) Shift work and cancer risk: potential mechanistic roles of circadian disruption, light at night, and sleep deprivation. Sleep Med Rev 17(4):273–284

    Article  PubMed  Google Scholar 

  45. Mazzoccoli G, Vinciguerra M, Papa G, Piepoli A (2014) Circadian clock circuitry in colorectal cancer. World J Gastroenterol 20(15):4197–4207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Joska TM, Zaman R, Belden WJ (2014) Regulated DNA methylation and the circadian clock: implications in cancer. Biology (Basel) 3(3):560–577

    CAS  Google Scholar 

  47. Tabung FK, Steck SE, Burch JB, et al. (2015) a healthy lifestyle index is associated with reduced risk of colorectal adenomatous polyps among non-users of non-steroidal anti-inflammatory drugs. J Prim Prev 36(1):21–31

  48. Winawer S, Fletcher R, Rex D et al (2003) Colorectal cancer screening and surveillance: clinical guidelines and rationale—update based on new evidence. Gastroenterology 124(2):544–560

    Article  PubMed  Google Scholar 

  49. Bender R, Lange S (2001) Adjusting for multiple testing—when and how? J Clin Epidemiol 54(4):343–349

    Article  CAS  PubMed  Google Scholar 

  50. Hawkins NJ, Ward RL (2001) Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas. J Natl Cancer Inst 93(17):1307–1313

    Article  CAS  PubMed  Google Scholar 

  51. Hebert JR, Gupta PC, Bhonsle RB et al (2002) Dietary exposures and oral precancerous lesions in Srikakulam District, Andhra Pradesh, India. Public Health Nutr 5(2):303–312

    Article  PubMed  Google Scholar 

  52. Suter CM, Norrie M, Ku SL, Cheong KF, Tomlinson I, Ward RL (2003) CpG island methylation is a common finding in colorectal cancer cell lines. Br J Cancer 88(3):413–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kim HC, Roh SA, Ga IH, Kim JS, Yu CS, Kim JC (2005) CpG island methylation as an early event during adenoma progression in carcinogenesis of sporadic colorectal cancer. J Gastroenterol Hepatol 20(12):1920–1926

    Article  CAS  PubMed  Google Scholar 

  54. Kim YH, Petko Z, Dzieciatkowski S et al (2006) CpG island methylation of genes accumulates during the adenoma progression step of the multistep pathogenesis of colorectal cancer. Genes Chromosomes Cancer 45(8):781–789

    Article  CAS  PubMed  Google Scholar 

  55. Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A (2002) CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol 160(5):1823–1830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. de Maat MF, Narita N, Benard A et al (2010) Development of sporadic microsatellite instability in colorectal tumors involves hypermethylation at methylated-in-tumor loci in adenoma. Am J Pathol. 177(5):2347–2356

    Article  PubMed  PubMed Central  Google Scholar 

  57. Worthley DL, Whitehall VL, Buttenshaw RL et al (2010) DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer. Oncogene 29(11):1653–1662

    Article  CAS  PubMed  Google Scholar 

  58. Gery S, Komatsu N, Baldjyan L, Yu A, Koo D, Koeffler HP (2006) The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol Cell 22(3):375–382

    Article  CAS  PubMed  Google Scholar 

  59. Brown SA, Ripperger J, Kadener S et al (2005) PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Science 308(5722):693–696

    Article  CAS  PubMed  Google Scholar 

  60. Sjoblom T, Jones S, Wood LD et al (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314(5797):268–274

    Article  PubMed  Google Scholar 

  61. Oshima T, Takenoshita S, Akaike M et al (2011) Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer. Oncol Rep. doi:10.3892/or.2011.1207

    Google Scholar 

  62. Wang X, Yan D, Teng M, et al. (2012) Reduced expression of PER3 is associated with incidence and development of colon cancer. Ann Surg Oncol 19(9):3081–3088

  63. Mostafaie N, Kallay E, Sauerzapf E et al (2009) Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer. Mol Carcinog 48(7):642–647

    Article  CAS  PubMed  Google Scholar 

  64. Krugluger W, Brandstaetter A, Kallay E et al (2007) Regulation of genes of the circadian clock in human colon cancer: reduced period-1 and dihydropyrimidine dehydrogenase transcription correlates in high-grade tumors. Cancer Res 67(16):7917–7922

    Article  CAS  PubMed  Google Scholar 

  65. Karantanos T, Theodoropoulos G, Gazouli M et al (2013) Expression of clock genes in patients with colorectal cancer. Int J Biol Markers 28(3):280–285

    Article  CAS  PubMed  Google Scholar 

  66. Alexander M, Burch JB, Steck SE et al (2015) Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation. Oncol Rep 33:935–941

    CAS  PubMed  Google Scholar 

  67. Mazzoccoli G, Palmieri O, Corritore G et al (2012) Association study of a polymorphism in clock gene PERIOD3 and risk of inflammatory bowel disease. Chronobiol Int 29(8):994–1003

    Article  CAS  PubMed  Google Scholar 

  68. Yang MY, Chang JG, Lin PM et al (2006) Downregulation of circadian clock genes in chronic myeloid leukemia: alternative methylation pattern of hPER3. Cancer Sci 97(12):1298–1307

    Article  CAS  PubMed  Google Scholar 

  69. Kuo SJ, Chen ST, Yeh KT et al (2009) Disturbance of circadian gene expression in breast cancer. Virchows Arch 454(4):467–474

    Article  CAS  PubMed  Google Scholar 

  70. Chen ST, Choo KB, Hou MF, Yeh KT, Kuo SJ, Chang JG (2005) Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis 26(7):1241–1246

    Article  CAS  PubMed  Google Scholar 

  71. Shih MC, Yeh KT, Tang KP, Chen JC, Chang JG (2006) Promoter methylation in circadian genes of endometrial cancers detected by methylation-specific PCR. Mol Carcinog 45(10):732–740

    Article  CAS  PubMed  Google Scholar 

  72. Gery S, Komatsu N, Kawamata N et al (2007) Epigenetic silencing of the candidate tumor suppressor gene Per1 in non-small cell lung cancer. Clin Cancer Res 13(5):1399–1404

    Article  CAS  PubMed  Google Scholar 

  73. Valekunja UK, Edgar RS, Oklejewicz M et al (2013) Histone methyltransferase MLL3 contributes to genome-scale circadian transcription. Proc Natl Acad Sci U S A 110(4):1554–1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Waldmann T, Schneider R (Apr 2013) Targeting histone modifications-epigenetics in cancer. Curr Opin Cell Biol 25(2):184–189

    Article  CAS  PubMed  Google Scholar 

  75. Watanabe Y, Castoro RJ, Kim HS et al (2011) Frequent alteration of MLL3 frameshift mutations in microsatellite deficient colorectal cancer. PLoS One 6(8):e23320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Duong HA, Weitz CJ (2014) Temporal orchestration of repressive chromatin modifiers by circadian clock period complexes. Nat Struct Mol Biol 21(2):126–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hancks DC, Kazazian HH Jr (2012) Active human retrotransposons: variation and disease. Curr Opin Genet Dev 22(3):191–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Miki Y, Nishisho I, Horii A et al (1992) Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res 52(3):643–645

    CAS  PubMed  Google Scholar 

  79. Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301(5895):89–92

    Article  CAS  PubMed  Google Scholar 

  80. Hancks DC, Kazazian HH Jr (2010) SVA retrotransposons: evolution and genetic instability. Semin Cancer Biol 20(4):234–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sabino FC, Ribeiro AO, Tufik S et al (2014) Evolutionary history of the PER3 variable number of tandem repeats (VNTR): idiosyncratic aspect of primate molecular circadian clock. PLoS One 9(9):e107198

    Article  PubMed  PubMed Central  Google Scholar 

  82. Cassinotti E, Melson J, Liggett T et al (2012) DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps. Int J Cancer 131(5):1153–1157

    Article  CAS  PubMed  Google Scholar 

  83. Adalsteinsson BT, Gudnason H, Aspelund T et al (2012) Heterogeneity in white blood cells has potential to confound DNA methylation measurements. PLoS One 7(10):e46705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hoffman AE, Yi CH, Zheng T et al (2010) CLOCK in breast tumorigenesis: genetic, epigenetic, and transcriptional profiling analyses. Cancer Res 70(4):1459–1468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Fu A, Leaderer D, Zheng T, Hoffman AE, Stevens RG, Zhu Y (2012) Genetic and epigenetic associations of circadian gene TIMELESS and breast cancer risk. Mol Carcinog 51(12):923-929

  86. Hoffman AE, Zheng T, Yi CH et al (2010) The core circadian gene cryptochrome 2 influences breast cancer risk, possibly by mediating hormone signaling. Cancer Prev Res 3(4):539–548

    Article  CAS  Google Scholar 

  87. Lahti T, Merikanto I, Partonen T (2012) Circadian clock disruptions and the risk of cancer. Ann Med 44(8):847–853

    Article  CAS  PubMed  Google Scholar 

  88. Bollati V, Baccarelli A, Sartori S et al (2010) Epigenetic effects of shiftwork on blood DNA methylation. Chronobiol Int 27(5):1093–1104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Bhatti P, Zhang Y, Song X et al (2014) Nightshift work and genome-wide DNA methylation. Chronobiol Int 4:1–10

    Google Scholar 

  90. Zhu Y, Stevens RG, Hoffman AE et al (2011) Epigenetic impact of long-term shiftwork: pilot evidence from circadian genes and whole-genome methylation analysis. Chronobiol Int 28(10):852–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Qureshi IA, Mehler MF (2014) Epigenetics of sleep and chronobiology. Curr Neurol Neurosci Rep 14(3):432

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the management, staff, and participating patients of the South Carolina Medical Endoscopy Center (Columbia, SC). Ms. Susannah Kassler and Ms. Amy Messersmith provided technical support with sample processing.

Statement of authors’ contributions

Drs. Burch, Steck, and Hébert designed the study and applied for Research Ethics Board approval. Dr. Stephen Lloyd, Dr. Alexander, and Ms. Guess recruited the patients and collected the data. Drs. Chen and Creek and Mr. Jones carried out all appropriate laboratory assays. Dr. Alexander prepared the manuscript draft with important intellectual input from all authors. All authors approved the final manuscript.

Author information

Authors and Affiliations

  1. South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA

    M. Alexander, J. B. Burch, S. E. Steck, T. G. Hurley, P. Cavicchia, N. Shivappa, J. Guess & J. R. Hébert

  2. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA

    M. Alexander, J. B. Burch, S. E. Steck, P. Cavicchia, N. Shivappa, J. Guess & J. R. Hébert

  3. William Jennings Bryant Dorn Department of Veterans Affairs Medical Center, Columbia, SC, USA

    J. B. Burch

  4. Center for Molecular Studies, Greenwood Genetic Center, Greenwood, SC, USA

    C.-F. Chen & K. Jones

  5. Division of Community Health Promotion, Florida Department of Health, Tallahassee, FL, USA

    P. Cavicchia

  6. Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA

    H. Zhang

  7. College of Nursing and Health Innovation, College of Health Solutions, Arizona State University and Phoenix VA Health Care System, Phoenix, AZ, USA

    S. D. Youngstedt

  8. Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA

    K. E. Creek

  9. South Carolina Medical Endoscopy Center, and Department of Family Medicine, University of South Carolina School of Medicine, Columbia, SC, USA

    S. Lloyd

  10. Department of Family and Preventive Medicine, School of Medicine, University of South Carolin, Columbia, SC, USA

    J. R. Hébert

Authors
  1. M. Alexander
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. B. Burch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. E. Steck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C.-F. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. G. Hurley
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Cavicchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N. Shivappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Guess
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S. D. Youngstedt
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. K. E. Creek
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S. Lloyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. K. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. J. R. Hébert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. B. Burch.

Ethics declarations

Prior to their enrollment in this study participants provided informed consent, including permission to access medical records, in accordance with the University of South Carolina’s Institutional Review Board approval process.

Funding

This work was supported by three grants from the National Cancer Institute (NCI)—an Administrative Supplement to the South Carolina Cancer Disparities Community Network (SCCDCN—3 U01 CA114601-03S5.PI: JR Hébert; co-project leaders: JB Burch, SE Steck), SCCDCN-II (1 U54 CA153461–01, JR Hebert, PI), and an Established Investigator Award in Cancer Prevention and Control from the Cancer Training Branch of the National Cancer Institute (K05 CA136975; JR Hébert, PI); a USC Research Opportunity Award (PI: SE Steck); the University of South Carolina Behavioral-Biomedical Interface Program with a grant from the National Institute of General Medical Sciences (T32-GM081740), which funded Melannie Alexander’s effort; and a grant from the National Center for Research Resources to the USC Center for Colon Cancer Research (COBRE 5P20RR017698), which supported a part of Dr. Steck’s effort.

Additional information

S. E. Steck and J. R. Hébert are co-senior authors (e.g., both were Principal Investigators of grants that supported this research).

Electronic supplementary material

Figure S1

(DOCX 401 kb)

Figure S2

(DOCX 340 kb)

Table S1

(DOCX 13 kb)

Table S2

(DOCX 15 kb)

Table S3

(DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alexander, M., Burch, J.B., Steck, S.E. et al. Case-control study of candidate gene methylation and adenomatous polyp formation. Int J Colorectal Dis 32, 183–192 (2017). https://doi.org/10.1007/s00384-016-2688-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-016-2688-1

Keywords

Search

Navigation