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Candidate gene association study of esophageal squamous cell carcinoma in a high-risk region in Iran

Akbari, M.R. and Malekzadeh, R. and Shakeri, R. and Nasrollahzadeh, D. and Foumani, M. and Sun, Y. and Pourshams, A. and Sadjadi, A. and Jafari, E. and Sotoudeh, M. and Kamangar, F. and Boffetta, P. and Dawsey, S.M. and Ghadirian, P. and Narod, S.A. (2009) Candidate gene association study of esophageal squamous cell carcinoma in a high-risk region in Iran. Cancer Research, 69 (20). pp. 7994-8000.

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Abstract

There is a region with a high risk for esophageal squamous cell carcinoma (ESCC) in the northeast of Iran. Previous studies suggest that hereditary factors play a role in the high incidence of cancer in the region. We selected 22 functional variants (and 130 related tagSNPs) from 15 genes that have been associated previously with the risk of ESCC. We genotyped a primary set of samples from 451 Turkmens (197 cases and 254 controls). Seven of 152 variants were associated with ESCC at the P = 0.05 level; these single nucleotide polymorphisms were then studied in a validation set of 549 cases and 1,119 controls, which included both Turkmens and non-Turkmens. The association observed for a functional variant in ADH1B was confirmed in the validation set, and that of a tagSNP in MGMT, the association was borderline significant in the validation set, after correcting for multiple testing. The other 5 variants that were associated in the primary set were not significantly associated in the validation set. The histidine allele at codon 48 of ADH1B gene was associated with a significantly decreased risk of ESCC in the joint data set (primary and validation set) under a recessive model (odds ratio, 0.41; 95 confidence interval, 0.29-0.76; P = 4 × 10⁻⁴). The A allele of the rs7087131 variant of MGMT gene was associated with a decreased risk of ESCC under a dominant model (odds ratio, 0.79; 95 confidence interval, 0.64-0.96; P = 0.02). These results support the hypothesis that genetic predisposition plays a role in the high incidence of ESSC in Iran. ©2009 American Association for Cancer Research.

Item Type: Article
Additional Information: cited By 18
Uncontrolled Keywords: alcohol dehydrogenase; alcohol dehydrogenase 1b; histidine; methylated DNA protein cysteine methyltransferase; unclassified drug, adult; aged; allele; article; cancer incidence; cancer risk; codon; controlled study; esophageal squamous cell carcinoma; female; gene expression; genetic association; genetic predisposition; genetic variability; genotype; high risk population; human; Iran; major clinical study; male; priority journal; single nucleotide polymorphism; Turkey (republic), Adult; Aged; Aged, 80 and over; Alcohol Dehydrogenase; Alleles; Carcinoma, Squamous Cell; Case-Control Studies; DNA Modification Methylases; DNA Repair Enzymes; Esophageal Neoplasms; Female; Genetic Predisposition to Disease; Genotype; Humans; Incidence; Iran; Male; Middle Aged; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prognosis; Risk Factors; Tumor Suppressor Proteins
Subjects: کهورت
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 21 Apr 2015 05:29
Last Modified: 27 Feb 2017 06:51
URI: http://eprints.goums.ac.ir/id/eprint/2588

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