Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Polymorphisms of the inflammatory pathway genes MPO -G463A and SOD2 Ala16Val are associated with elevated pancreatic cancer risk. Oxidative stress may play an important role in pancreatic cancer carcinogenesis.
Wheatley-Price
Paul
P
Department of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Hospital, Toronto, Ontario, Canada.
Asomaning
Kofi
K
Reid
Amy
A
Zhai
Rihong
R
Su
Li
L
Zhou
Wei
W
Zhu
Andrew
A
Ryan
David P
DP
Christiani
David C
DC
Liu
Geoffrey
G
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D013482:Superoxide Dismutase / Q000235:genetics*
D009195:Peroxidase; D013482:Superoxide Dismutase