There is evidence that chronic
inflammation predisposes to
biliary tract cancer and that use of non-steroidal anti-inflammatory drugs (
NSAIDs) is protective. Although the mechanisms by which
NSAIDs lower
cancer risk remain unclear,
NSAIDs reduce
prostaglandin production by blocking
prostaglandin-endoperoxide synthase 2 (
PTGS2, commonly known as COX-2), an
enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue. Since variants in the
PTGS2 gene may modify the expression or function of its encoded
enzyme to modulate the inflammatory response in the biliary tract, we examined the associations of eight
PTGS2 polymorphisms (-645C-->T; Ex3 -8G-->C; IVS5 -275T-->G; IVS7 +111T-->C; Ex10 +127T-->C; Ex10 +686 --->ATTAT-->TTATA; Ex10 +837T-->C; Ex10 -90C-->T) with
biliary tract cancer and stones in a population-based case-control study conducted in Shanghai, China. Genotyping was performed for 411 patients with
biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater), 895 patients with biliary stones (673 gallbladder, 222 bile duct), and 786 healthy individuals randomly selected from the population. Significant associations were seen only between the Ex10 +837T-->C marker and
bile duct cancer risk. Relative to individuals with the TT genotype, those carrying the C allele (TC or CC genotype) had a 1.8-fold (95% confidence interval: 1.2-2.7) risk of
bile duct cancer. Inferred haplotypes including this risk-conferring allele were also associated with increased
bile duct cancer risk of similar magnitude. Our results suggest that a common
PTGS2 variant increases
bile duct cancer risk. Further investigation is needed to confirm and extend our findings in studies of
biliary tract cancer that more comprehensively examine
PTGS2 and other
inflammation-related genes.