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Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma
Article first published online: 18 JAN 2008
Copyright © 2008 American Cancer Society
Volume 112, Issue 5, pages 1037–1042, March 2008
How to Cite
Wheatley-Price, P., Asomaning, K., Reid, A., Zhai, R., Su, L., Zhou, W., Zhu, A., Ryan, D. P., Christiani, D. C. and Liu, G. (2008), Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma. Cancer, 112: 1037–1042. doi: 10.1002/cncr.23267
- Issue published online: 19 FEB 2008
- Article first published online: 18 JAN 2008
- Manuscript Accepted: 18 SEP 2007
- Manuscript Revised: 31 AUG 2007
- Manuscript Received: 30 JUL 2007
- superoxide dismutase;
- pancreatic cancer
Pancreatic cancer risk has been linked to chronic pancreatitis and periodontitis, suggesting a role for inflammation in disease etiology. Myeloperoxidase (MPO) and superoxide dismutase (SOD2) are enzymes that regulate reactive oxygen species and contain recognized single nucleotide polymorphisms (SNPs) that confer altered enzyme activity.
One hundred twenty-two patients with pancreatic cancer and 331 age- and sex-matched controls were analyzed for polymorphisms of the MPO − guanine 463 adenine (−G463A) and the SOD2 alanine (Ala)-to-valine (Val) polymorphism at codon 16 (Ala16Val) genes. Cases and controls were analyzed for associations between these polymorphisms, adjusting for sex, age, history of alcohol use and smoking history.
The variant A allele of MPO −G463A was associated with a lower risk of pancreatic cancer (adjusted odds ratio [OR] for pancreatic cancer, 0.57; 95% confidence interval [95% CI], 0.4–0.9; P = .02). The SOD2 homozygous variant genotype (Val/Val) was associated with a greater risk of pancreatic cancer (adjusted OR, 1.96; 95% CI, 1.0–3.8; P = .04). Compared with individuals who carried both low-risk alleles (A/− and Ala/−), significantly more cases than controls carried both high-risk genotypes (G/G and Val/Val; adjusted OR, 4.31; 95% CI, 1.8–10; P = .001), or 1 high-risk genotype (adjusted OR, 1.96; 95% CI, 1.1–3.4; P = .01).
Polymorphisms of the inflammatory pathway genes MPO −G463A and SOD2Ala16Val are associated with elevated pancreatic cancer risk. Oxidative stress may play an important role in pancreatic cancer carcinogenesis. Cancer 2008. © 2008 American Cancer Society.