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No Association between hOGG1, XRCC1, and XPD Polymorphisms and Risk of Reflux Esophagitis, Barrett's Esophagus, or Esophageal Adenocarcinoma: Results from the Factors Influencing the Barrett's Adenocarcinoma Relationship Case-Control Study

¹ Division of Gastroenterology, Belfast City Hospital; ² Centre for Clinical and Population Sciences, Queen's University; Divisions of ³ Gastroenterology and ⁴ Surgery, Royal Group of Hospitals, Belfast, United Kingdom; ⁵ Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, United Kingdom; ⁶ Division of Gastroenterology, Daisy Hill Hospital, Newry, United Kingdom; and ⁷ Division of Surgery, St. James's Hospital, Dublin, Ireland

Requests for reprints: Heather R. Ferguson, Level 6 North, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland. Phone: 44-2890-632602; Fax: 44-2890-231907. E-mail: hrferguson{at}doctors.net.uk

Reflux of gastric contents can lead to development of reflux esophagitis and Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal adenocarcinoma. Damage to DNA may lead to carcinogenesis but is repaired through activation of pathways involving polymorphic enzymes, including human 8-oxoguanine glycosylase 1 (hOGG1), X-ray repair cross-complementing 1 (XRCC1), and xeroderma pigmentosum group D (XPD). Of the single nucleotide polymorphisms identified in these genes, hOGG1 Ser³²⁶Cys, XRCC1 Arg³⁹⁹Gln, and XPD Lys⁷⁵¹Gln are particularly common in Caucasians and have been associated with lower DNA repair capacity. Small studies have reported associations with XPD Lys⁷⁵¹Gln and esophageal adenocarcinoma. XRCC1 Arg³⁹⁹Gln has been linked to Barrett's esophagus and reflux esophagitis. In a population-based case-control study, we examined associations of the hOGG1 Ser³²⁶Cys, XRCC1 Arg³⁹⁹Gln, and XPD Lys⁷⁵¹Gln polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), reflux esophagitis (n = 230), and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. There were no statistically significant associations between these polymorphisms and risk of esophageal adenocarcinoma, Barrett's esophagus, or reflux esophagitis. (Cancer Epidemiol Biomarkers Prev 2008;17(3):736–9)