The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case–control study in Sweden (original) (raw)

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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet

Stockholm, SE 171 77, Sweden

* To whom correspondence should be addressed at: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE 171 77, Stockholm, Sweden. Tel: +46 8 52486184; Fax: +46 8 314975; Email: Weimin.Ye@ki.se

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Division of Molecular Genetic Epidemiology, German Cancer Research Center

69120 Heidelberg, Germany

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Department of Bioscience at Novum, Karolinska Institutet

Stockholm, SE 141 57, Sweden

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Department of Bioscience at Novum, Karolinska Institutet

Stockholm, SE 141 57, Sweden

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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet

Stockholm, SE 171 77, Sweden

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Unit of Esophageal and Gastric Research, Department of Molecular Medicine and Surgery, Karolinska Institutet

Stockholm, SE 171 76, Sweden

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Division of Molecular Genetic Epidemiology, German Cancer Research Center

69120 Heidelberg, Germany

33

Department of Bioscience at Novum, Karolinska Institutet

Stockholm, SE 141 57, Sweden

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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet

Stockholm, SE 171 77, Sweden

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Received:

14 October 2005

Revision received:

08 March 2006

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Weimin Ye, Rajiv Kumar, Gabriela Bacova, Jesper Lagergren, Kari Hemminki, Olof Nyrén, The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case–control study in Sweden , Carcinogenesis, Volume 27, Issue 9, September 2006, Pages 1835–1841, https://doi.org/10.1093/carcin/bgl017
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Abstract

Mechanisms behind the strong associations of esophageal adenocarcinoma risk with gastroesophageal reflux (GOR) and body mass remain to be defined. In a nationwide population-based case–control study, we examined associations of polymorphisms in the DNA repair genes XPD, XPC, XRCC1 and XRCC3 with risk of esophageal adenocarcinoma, squamous-cell carcinoma (SCC) and gastric cardia adenocarcinoma, and paid special attention to possible interactions with symptomatic reflux or body mass. We collected blood samples from 96, 81 and 126 interviewed incident cases of esophageal adenocarcinoma, esophageal SCC and gastric cardia adenocarcinoma, respectively, and 472 randomly selected controls, frequency-matched with regard to age and sex. DNA was extracted and polymorphisms in XPD codon 751 (Lys→Gln), codon 312 (Asp→Asn), C insertion in intron 10 of XPD, XPC codon 939 (Lys→Gln), XRCC1 codon 399 (Arg→Gln) and XRCC3 codon 241 (Thr→Met) were examined using PCR–RFLP. Odds ratios (ORs) derived from multivariate logistic regression with adjustments for potential confounding factors estimated relative risks. XPD codon 751 Lys/Gln and Gln/Gln genotypes, compared with Lys/Lys genotype, were both associated with a more than doubled risk for esophageal adenocarcinoma (OR = 2.4; 95% CI = 1.4–4.4; OR = 2.7, 95% CI = 1.3–5.9). The combined effects of these genotypes and symptomatic GOR or body mass showed borderline significant deviation from additivity. Excess risks for esophageal SCC were also noted for XPD 751Gln variant genotypes. Other studied variants were not found to be related to the three tumors. Our study suggests that XPD 751Gln allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma.

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Topic:

• alleles
• polymerase chain reaction
• polymorphism
• squamous cell carcinoma
• esophageal adenocarcinoma
• gastroesophageal reflux disease
• codon nucleotides
• dna
• genotype
• introns
• lysine
• restriction fragment length polymorphism
• genetic markers
• glutamine
• neoplasms
• squamous cell carcinoma, esophageal
• dna repair gene
• gastric cardia adenocarcinoma
• ercc2 gene
• xrcc1 gene

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