Characterization of the colorectal cancer-associated enhancer MYC-335 at 8q24: The role of rs67491583

Sari Tuupanen, Jian Yan, Mikko Turunen, Alexandra E. Gylfe, Eevi Kaasinen, Li Li, Charis Eng, Daniel A. Culver, Matthew F. Kalady, Michael J. Pennison, Boris Pasche, Upender Manne, Albert de la Chapelle, Heather Hampel, Brian E. Henderson, Loic Le Marchand, Sampsa Hautaniemi, Hassan Askhtorab, Duane Smoot, Robert S. SandlerTemitope Keku, Sonia S. Kupfer, Nathan A. Ellis, Christopher A. Haiman, Jussi Taipale, Lauri A. Aaltonen

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Recent genome-wide association studies have identified multiple regions at 8q24 that confer susceptibility to many cancers. In our previous work, we showed that the colorectal cancer (CRC) risk variant rs6983267 at 8q24 resides within a TCF4 binding site at the MYC-335 enhancer, with the risk allele G having a stronger binding capacity and Wnt responsiveness. Here, we searched for other potential functional variants within MYC-335. Genetic variation within MYC-335 was determined in samples from individuals of European, African, and Asian descent, with emphasis on variants in putative transcription factor binding sites. A 2-bp GA deletion rs67491583 was found to affect a growth factor independent (GFI) binding site and was present only in individuals with African ancestry. Chromatin immunoprecipitation performed in heterozygous cells showed that the GA deletion had an ability to reduce binding of the transcriptional repressors GFI1 and GFI1b. Screening of 1,027 African American colorectal cancer cases and 1,773 healthy controls did not reveal evidence for association (odds ratio: 1.17, 95% confidence interval: 0.97-1.41, P = 0.095). In this study, rs67491583 was identified as another functional variant in the CRC-associated enhancer MYC-335, but further studies are needed to establish the role of rs67491583 in the colorectal cancer predisposition of African Americans.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalCancer Genetics
Issue number1-2
StatePublished - Jan 2012


  • Association
  • Colorectal cancer
  • Enhancer
  • Susceptibility variant
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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