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. 2008 Dec;19(10):1077-83.
doi: 10.1007/s10552-008-9171-4. Epub 2008 May 14.

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Darren Tse  1 , Rihong Zhai, Wei Zhou, Rebecca S Heist, Kofi Asomaning, Li Su, Thomas J Lynch, John C Wain, David C Christiani, Geoffrey Liu
Affiliations

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Darren Tse et al. Cancer Causes Control. 2008 Dec.

Abstract

Purpose: Functional variation in DNA repair capacity through single nucleotide polymorphisms (SNPs) of key repair genes is associated with a higher risk of developing various types of cancer. Studies have focused on the nucleotide excision repair (NER) and base excision repair (BER) pathways. We investigated whether variant alleles in seven SNPs within these pathways increased the risk of esophageal adenocarcinoma.

Methods: DNA was extracted from prospectively collected blood specimens. The samples were genotyped for SNPs in NER genes (XPD Lys751Gln, XPD Asp312Asn, ERCC1 8092C/A, and ERCC1 118C/T), and BER genes (XRCC1 Arg399Gln, APE1 Asp148Glu, and hOGG1 Ser326Cys). The presence of variant alleles was correlated with risk of esophageal adenocarcinoma both individually and jointly.

Results: Variant alleles in NER SNPs XPD Lys751Gln (AOR = 1.50, 95% CI 1.1-2.0), ERCC1 8092 C/A (AOR = 1.44, 95% CI 1.1-1.9), and ERCC1 118C/T (AOR = 1.42, 95% CI 1.0-1.9) were individually associated with esophageal adenocarcinoma risk. An increasing number of variant alleles in NER SNPs showed a significant trend with esophageal adenocarcinoma risk (p = 0.007).

Conclusions: The presence of variant alleles in NER genes increases risk of esophageal adenocarcinoma. There is evidence of an additive role for SNPs along a common DNA repair pathway. Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways.

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References

    1. Devesa SS, Blot WJ, Fraumeni JF., Jr Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. 1998;83(10):2049–2053. - PubMed
    1. Younes M, Henson DE, Ertan A, Miller CC. Incidence and survival trends of esophageal carcinoma in the United States: racial and gender differences by histological type. Scand J Gastroenterol. 2002;37(12):1359–1365. - PubMed
    1. Ilson DH. Oesophageal cancer: new developments in systemic therapy. Cancer Treat Rev. 2003;29(6):525–532. - PubMed
    1. Holmes RS, Vaughan TL. Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol. 2007;17(1):2–9. - PubMed
    1. Siewert JR, Ott K. Are squamous and adenocarcinomas of the esophagus the same disease? Semin Radiat Oncol. 2007;17(1):38–44. - PubMed

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