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 XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based casecontrol study in Sweden
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 casecontrol 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 PCRRFLP. 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 = 1.44.4; OR = 2.7, 95% CI = 1.35.9). 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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