Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype

Dallas R. English, Joanne P. Young, Julie A. Simpson, Mark A. Jenkins, Melissa C. Southey, Michael D. Walsh, Daniel D. Buchanan, Melissa A. Barker, Andrew M. Haydon, Simon G. Royce, Aedan Roberts, Susan Parry, John Hopper, Jeremy J. Jass, Graham G. Giles

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Abstract

Colorectal cancers arising from serrated polyps are characterized by the CpG island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto-oncogene. Few epidemiologic studies have investigated risk factors for these tumors. We conducted a cohort study of 41,328 residents of Melbourne, Australia that included 9,939 participants of southern European origin and 31,389 of Anglo-Celtic origin. Colorectal adenocarcinomas were identified from population-based cancer registries. BRAF V600E mutation in tumors was determined using a PCR-based allelic discrimination method. Tumors were classified as CIMP positive when at least three of five markers (RUNX3, CACNA1G, SOCS1, NEUROG1, and IGF2) were methylated according to MethyLight analysis. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression with adjustment for risk factors for colorectal cancer. During follow-up, 718 participants were diagnosed with colorectal cancer. CIMP assays were done for 579 and BRAF V600E mutation testing for 582. After adjustment for other risk factors, when compared with people of Anglo-Celtic origin, those of southern European origin had lower incidence of colorectal cancer that had CIMP (HR, 0.32; 95% CI, 0.16-0.67) or BRAF mutations (HR, 0.30; 95% CI, 0.16-0.58) but similar incidence of colorectal cancer without CIMP (HR, 0.86; 95% CI, 0.70-1.05) or BRAF (HR, 0.90; 95% CI, 0.74-1.11). People of southern European origin had lower risk of colorectal cancers with CIMP and BRAF mutation than people of Anglo-Celtic origin, which may in part be due to genetic factors that are less common in people of southern European origin.

Original languageEnglish
Pages (from-to)1774-1780
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 2008
Externally publishedYes

Cite this

English, Dallas R. ; Young, Joanne P. ; Simpson, Julie A. ; Jenkins, Mark A. ; Southey, Melissa C. ; Walsh, Michael D. ; Buchanan, Daniel D. ; Barker, Melissa A. ; Haydon, Andrew M. ; Royce, Simon G. ; Roberts, Aedan ; Parry, Susan ; Hopper, John ; Jass, Jeremy J. ; Giles, Graham G. / Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype. In: Cancer Epidemiology Biomarkers and Prevention. 2008 ; Vol. 17, No. 7. pp. 1774-1780.
@article{5e0c17fc4bc54b65a4d5190fd479bc84,
title = "Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype",
abstract = "Colorectal cancers arising from serrated polyps are characterized by the CpG island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto-oncogene. Few epidemiologic studies have investigated risk factors for these tumors. We conducted a cohort study of 41,328 residents of Melbourne, Australia that included 9,939 participants of southern European origin and 31,389 of Anglo-Celtic origin. Colorectal adenocarcinomas were identified from population-based cancer registries. BRAF V600E mutation in tumors was determined using a PCR-based allelic discrimination method. Tumors were classified as CIMP positive when at least three of five markers (RUNX3, CACNA1G, SOCS1, NEUROG1, and IGF2) were methylated according to MethyLight analysis. Hazard ratios (HR) and 95{\%} confidence intervals (95{\%} CI) were estimated by Cox regression with adjustment for risk factors for colorectal cancer. During follow-up, 718 participants were diagnosed with colorectal cancer. CIMP assays were done for 579 and BRAF V600E mutation testing for 582. After adjustment for other risk factors, when compared with people of Anglo-Celtic origin, those of southern European origin had lower incidence of colorectal cancer that had CIMP (HR, 0.32; 95{\%} CI, 0.16-0.67) or BRAF mutations (HR, 0.30; 95{\%} CI, 0.16-0.58) but similar incidence of colorectal cancer without CIMP (HR, 0.86; 95{\%} CI, 0.70-1.05) or BRAF (HR, 0.90; 95{\%} CI, 0.74-1.11). People of southern European origin had lower risk of colorectal cancers with CIMP and BRAF mutation than people of Anglo-Celtic origin, which may in part be due to genetic factors that are less common in people of southern European origin.",
author = "English, {Dallas R.} and Young, {Joanne P.} and Simpson, {Julie A.} and Jenkins, {Mark A.} and Southey, {Melissa C.} and Walsh, {Michael D.} and Buchanan, {Daniel D.} and Barker, {Melissa A.} and Haydon, {Andrew M.} and Royce, {Simon G.} and Aedan Roberts and Susan Parry and John Hopper and Jass, {Jeremy J.} and Giles, {Graham G.}",
year = "2008",
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doi = "10.1158/1055-9965.EPI-08-0091",
language = "English",
volume = "17",
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English, DR, Young, JP, Simpson, JA, Jenkins, MA, Southey, MC, Walsh, MD, Buchanan, DD, Barker, MA, Haydon, AM, Royce, SG, Roberts, A, Parry, S, Hopper, J, Jass, JJ & Giles, GG 2008, 'Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype', Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 7, pp. 1774-1780. https://doi.org/10.1158/1055-9965.EPI-08-0091

Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype. / English, Dallas R.; Young, Joanne P.; Simpson, Julie A.; Jenkins, Mark A.; Southey, Melissa C.; Walsh, Michael D.; Buchanan, Daniel D.; Barker, Melissa A.; Haydon, Andrew M.; Royce, Simon G.; Roberts, Aedan; Parry, Susan; Hopper, John; Jass, Jeremy J.; Giles, Graham G.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 17, No. 7, 07.2008, p. 1774-1780.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype

AU - English, Dallas R.

AU - Young, Joanne P.

AU - Simpson, Julie A.

AU - Jenkins, Mark A.

AU - Southey, Melissa C.

AU - Walsh, Michael D.

AU - Buchanan, Daniel D.

AU - Barker, Melissa A.

AU - Haydon, Andrew M.

AU - Royce, Simon G.

AU - Roberts, Aedan

AU - Parry, Susan

AU - Hopper, John

AU - Jass, Jeremy J.

AU - Giles, Graham G.

PY - 2008/7

Y1 - 2008/7

N2 - Colorectal cancers arising from serrated polyps are characterized by the CpG island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto-oncogene. Few epidemiologic studies have investigated risk factors for these tumors. We conducted a cohort study of 41,328 residents of Melbourne, Australia that included 9,939 participants of southern European origin and 31,389 of Anglo-Celtic origin. Colorectal adenocarcinomas were identified from population-based cancer registries. BRAF V600E mutation in tumors was determined using a PCR-based allelic discrimination method. Tumors were classified as CIMP positive when at least three of five markers (RUNX3, CACNA1G, SOCS1, NEUROG1, and IGF2) were methylated according to MethyLight analysis. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression with adjustment for risk factors for colorectal cancer. During follow-up, 718 participants were diagnosed with colorectal cancer. CIMP assays were done for 579 and BRAF V600E mutation testing for 582. After adjustment for other risk factors, when compared with people of Anglo-Celtic origin, those of southern European origin had lower incidence of colorectal cancer that had CIMP (HR, 0.32; 95% CI, 0.16-0.67) or BRAF mutations (HR, 0.30; 95% CI, 0.16-0.58) but similar incidence of colorectal cancer without CIMP (HR, 0.86; 95% CI, 0.70-1.05) or BRAF (HR, 0.90; 95% CI, 0.74-1.11). People of southern European origin had lower risk of colorectal cancers with CIMP and BRAF mutation than people of Anglo-Celtic origin, which may in part be due to genetic factors that are less common in people of southern European origin.

AB - Colorectal cancers arising from serrated polyps are characterized by the CpG island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto-oncogene. Few epidemiologic studies have investigated risk factors for these tumors. We conducted a cohort study of 41,328 residents of Melbourne, Australia that included 9,939 participants of southern European origin and 31,389 of Anglo-Celtic origin. Colorectal adenocarcinomas were identified from population-based cancer registries. BRAF V600E mutation in tumors was determined using a PCR-based allelic discrimination method. Tumors were classified as CIMP positive when at least three of five markers (RUNX3, CACNA1G, SOCS1, NEUROG1, and IGF2) were methylated according to MethyLight analysis. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression with adjustment for risk factors for colorectal cancer. During follow-up, 718 participants were diagnosed with colorectal cancer. CIMP assays were done for 579 and BRAF V600E mutation testing for 582. After adjustment for other risk factors, when compared with people of Anglo-Celtic origin, those of southern European origin had lower incidence of colorectal cancer that had CIMP (HR, 0.32; 95% CI, 0.16-0.67) or BRAF mutations (HR, 0.30; 95% CI, 0.16-0.58) but similar incidence of colorectal cancer without CIMP (HR, 0.86; 95% CI, 0.70-1.05) or BRAF (HR, 0.90; 95% CI, 0.74-1.11). People of southern European origin had lower risk of colorectal cancers with CIMP and BRAF mutation than people of Anglo-Celtic origin, which may in part be due to genetic factors that are less common in people of southern European origin.

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U2 - 10.1158/1055-9965.EPI-08-0091

DO - 10.1158/1055-9965.EPI-08-0091

M3 - Article

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EP - 1780

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

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