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. Sandler; Temitope Keku; Sonia S. Kupfer; Nathan A. Ellis; Christopher A. Haiman; Jussi Taipale; Lauri A. Aaltonen

doi:10.1016/j.cancergen.2012.01.005

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 journal › Article › peer-review

20 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	25-33
Number of pages	9
Journal	Cancer Genetics
Volume	205
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cancergen.2012.01.005
State	Published - Jan 2012
Externally published	Yes

Keywords

Association
Colorectal cancer
Enhancer
Susceptibility variant
Transcription factor

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1016/j.cancergen.2012.01.005

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Tuupanen, S., Yan, J., Turunen, M., Gylfe, A. E., Kaasinen, E., Li, L., Eng, C., Culver, D. A., Kalady, M. F., Pennison, M. J., Pasche, B., Manne, U., de la Chapelle, A., Hampel, H., Henderson, B. E., Le Marchand, L., Hautaniemi, S., Askhtorab, H., Smoot, D., ... Aaltonen, L. A. (2012). Characterization of the colorectal cancer-associated enhancer MYC-335 at 8q24: The role of rs67491583. Cancer Genetics, 205(1-2), 25-33. https://doi.org/10.1016/j.cancergen.2012.01.005

Tuupanen, S, Yan, J, Turunen, M, Gylfe, AE, Kaasinen, E, Li, L, Eng, C, Culver, DA, Kalady, MF, Pennison, MJ, Pasche, B, Manne, U, de la Chapelle, A, Hampel, H, Henderson, BE, Le Marchand, L, Hautaniemi, S, Askhtorab, H, Smoot, D, Sandler, RS, Keku, T, Kupfer, SS, Ellis, NA, Haiman, CA, Taipale, J & Aaltonen, LA 2012, 'Characterization of the colorectal cancer-associated enhancer MYC-335 at 8q24: The role of rs67491583', Cancer Genetics, vol. 205, no. 1-2, pp. 25-33. https://doi.org/10.1016/j.cancergen.2012.01.005

@article{b3a487f337e0482fa77724e314155603,

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

abstract = "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.",

keywords = "Association, Colorectal cancer, Enhancer, Susceptibility variant, Transcription factor",

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

note = "Funding Information: We thank Mairi Kuris, Inga-Lill Svedberg, Iina Vuoristo, Maarit Ohranen, and Sini Miettinen for technical assistance. This work was supported by the grants from Academy of Finland (Finnish Center of Excellence Program 2006–2011); the Finnish Cancer Society ; the Sigrid Juselius Foundation ; and the National Institutes of Health [ R01 CA66635 to R.S.S, CA67941 and CA16058 to A.d.l.C]. ",

year = "2012",

month = jan,

doi = "10.1016/j.cancergen.2012.01.005",

language = "English (US)",

volume = "205",

pages = "25--33",

journal = "Cancer Genetics",

issn = "2210-7762",

publisher = "Elsevier Inc.",

number = "1-2",

}

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T1 - Characterization of the colorectal cancer-associated enhancer MYC-335 at 8q24

T2 - The role of rs67491583

AU - Tuupanen, Sari

AU - Yan, Jian

AU - Turunen, Mikko

AU - Gylfe, Alexandra E.

AU - Kaasinen, Eevi

AU - Li, Li

AU - Eng, Charis

AU - Culver, Daniel A.

AU - Kalady, Matthew F.

AU - Pennison, Michael J.

AU - Pasche, Boris

AU - Manne, Upender

AU - de la Chapelle, Albert

AU - Hampel, Heather

AU - Henderson, Brian E.

AU - Le Marchand, Loic

AU - Hautaniemi, Sampsa

AU - Askhtorab, Hassan

AU - Smoot, Duane

AU - Sandler, Robert S.

AU - Keku, Temitope

AU - Kupfer, Sonia S.

AU - Ellis, Nathan A.

AU - Haiman, Christopher A.

AU - Taipale, Jussi

AU - Aaltonen, Lauri A.

N1 - Funding Information: We thank Mairi Kuris, Inga-Lill Svedberg, Iina Vuoristo, Maarit Ohranen, and Sini Miettinen for technical assistance. This work was supported by the grants from Academy of Finland (Finnish Center of Excellence Program 2006–2011); the Finnish Cancer Society ; the Sigrid Juselius Foundation ; and the National Institutes of Health [ R01 CA66635 to R.S.S, CA67941 and CA16058 to A.d.l.C].

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Association

KW - Colorectal cancer

KW - Enhancer

KW - Susceptibility variant

KW - Transcription factor

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

Abstract

Keywords

ASJC Scopus subject areas

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