Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries

Annie O. Chan, Amr S Soliman, Qing Zhang, Asif Rashid, Ahmed Bedeir, P. Scott Houlihan, Nadia Mokhtar, Nidal Al-Masri, Ugur Ozbek, Rami Yaghan, Ayten Kandilci, Sherif Omar, Yersu Kapran, Ferhunde Dizdaroglu, Melissa L. Bondy, Christopher I. Amos, Jean Pierre Issa, Bernard Levin, Stanley R. Hamilton

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Abstract

Purpose: The epidemiology of colorectal carcinoma is well known to differ among countries but the molecular characteristics are usually assumed to be similar. International differences in molecular pathology have not been studied extensively but have implications for the management of patients in different countries and of immigrant patients. Experimental Design: We evaluated the CpG island methylator phenotype pathway characterized by concordant methylation of gene promoters that often silences transcription of the genes, the microsatellite instability pathway, and K-ras and p53 gene status in 247 colorectal carcinomas from the three selected Middle Eastern countries of Egypt, Jordan, and Turkey. Results: Colorectal carcinoma from Egypt had the lowest frequencies of methylation. In multinomial logistic regression analysis, Jordanian colorectal carcinoma more frequently had methylation involving the p16 tumor suppressor gene (odds ratio, 3.5; 95% confidence interval, 1.2-10.6; P = 0.023) and MINT31 locus (odds ratio, 2.3; 95% confidence interval, 1.0-5.1; P = 0.041). The K-ras proto-oncogene was more frequently mutated in colorectal carcinoma from Turkey (odds ratio, 2.9; 95% confidence interval, 1.2-6.7; P = 0.016), but p53 overexpression was more common in both Jordanian and Turkish colorectal carcinoma than in Egyptian cases (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = 0.019; and odds ratio, 3.6; 95% confidence interval, 1.8-7.1; P = 0.0003, respectively). The findings in Turkish colorectal carcinoma were most similar to those reported for Western cases. Conclusions: Colorectal carcinoma from Middle Eastern countries have differing gene methylation patterns and mutation frequencies that indicate dissimilar molecular pathogenesis, probably reflecting different environmental exposures. These molecular differences could affect prevention strategies, therapeutic efficacy, and transferability of clinical trial results.

Original languageEnglish (US)
Pages (from-to)8281-8287
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number23
DOIs
StatePublished - Dec 1 2005

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Mutation Rate
DNA Methylation
Gene Frequency
Colorectal Neoplasms
Odds Ratio
Methylation
Confidence Intervals
ras Genes
Egypt
Turkey
Genes
Jordan
Microsatellite Instability
CpG Islands
Proto-Oncogenes
Molecular Pathology
p53 Genes
Environmental Exposure
Tumor Suppressor Genes
Epidemiology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chan, A. O., Soliman, A. S., Zhang, Q., Rashid, A., Bedeir, A., Houlihan, P. S., ... Hamilton, S. R. (2005). Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries. Clinical Cancer Research, 11(23), 8281-8287. https://doi.org/10.1158/1078-0432.CCR-05-1000

Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries. / Chan, Annie O.; Soliman, Amr S; Zhang, Qing; Rashid, Asif; Bedeir, Ahmed; Houlihan, P. Scott; Mokhtar, Nadia; Al-Masri, Nidal; Ozbek, Ugur; Yaghan, Rami; Kandilci, Ayten; Omar, Sherif; Kapran, Yersu; Dizdaroglu, Ferhunde; Bondy, Melissa L.; Amos, Christopher I.; Issa, Jean Pierre; Levin, Bernard; Hamilton, Stanley R.

In: Clinical Cancer Research, Vol. 11, No. 23, 01.12.2005, p. 8281-8287.

Research output: Contribution to journalArticle

Chan, AO, Soliman, AS, Zhang, Q, Rashid, A, Bedeir, A, Houlihan, PS, Mokhtar, N, Al-Masri, N, Ozbek, U, Yaghan, R, Kandilci, A, Omar, S, Kapran, Y, Dizdaroglu, F, Bondy, ML, Amos, CI, Issa, JP, Levin, B & Hamilton, SR 2005, 'Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries', Clinical Cancer Research, vol. 11, no. 23, pp. 8281-8287. https://doi.org/10.1158/1078-0432.CCR-05-1000
Chan, Annie O. ; Soliman, Amr S ; Zhang, Qing ; Rashid, Asif ; Bedeir, Ahmed ; Houlihan, P. Scott ; Mokhtar, Nadia ; Al-Masri, Nidal ; Ozbek, Ugur ; Yaghan, Rami ; Kandilci, Ayten ; Omar, Sherif ; Kapran, Yersu ; Dizdaroglu, Ferhunde ; Bondy, Melissa L. ; Amos, Christopher I. ; Issa, Jean Pierre ; Levin, Bernard ; Hamilton, Stanley R. / Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 23. pp. 8281-8287.
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AU - Chan, Annie O.

AU - Soliman, Amr S

AU - Zhang, Qing

AU - Rashid, Asif

AU - Bedeir, Ahmed

AU - Houlihan, P. Scott

AU - Mokhtar, Nadia

AU - Al-Masri, Nidal

AU - Ozbek, Ugur

AU - Yaghan, Rami

AU - Kandilci, Ayten

AU - Omar, Sherif

AU - Kapran, Yersu

AU - Dizdaroglu, Ferhunde

AU - Bondy, Melissa L.

AU - Amos, Christopher I.

AU - Issa, Jean Pierre

AU - Levin, Bernard

AU - Hamilton, Stanley R.

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