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Carcinogenesis Advance Access originally published online on March 29, 2006
Carcinogenesis 2006 27(9):1835-1841; doi:10.1093/carcin/bgl017
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Weimin Ye1,*, Rajiv Kumar2,3, Gabriela Bacova3, Jesper Lagergren1,4, Kari Hemminki2,3 and Olof Nyrén1

1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet Stockholm, SE 171 77, Sweden
2 Division of Molecular Genetic Epidemiology, German Cancer Research Center 69120 Heidelberg, Germany
3 Department of Bioscience at Novum, Karolinska Institutet Stockholm, SE 141 57, Sweden
4 Unit of Esophageal and Gastric Research, Department of Molecular Medicine and Surgery, Karolinska Institutet Stockholm, SE 171 76, 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{at}ki.se

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.


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