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Meta-Analysis
. 2013 May 22;8(5):e64122.
doi: 10.1371/journal.pone.0064122. Print 2013.

Genetic variation in 15-hydroxyprostaglandin dehydrogenase and colon cancer susceptibility

Cheryl L Thompson  1 , Stephen P Fink, James D Lutterbaugh, Robert C Elston, Martina L Veigl, Sanford D Markowitz, Li Li
Affiliations
Meta-Analysis

Genetic variation in 15-hydroxyprostaglandin dehydrogenase and colon cancer susceptibility

Cheryl L Thompson et al. PLoS One. .

Abstract

Background: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a metabolic antagonist of COX-2, catalyzing the degradation of inflammation mediator prostaglandin E2 (PGE2) and other prostanoids. Recent studies have established the 15-PGDH gene as a colon cancer suppressor.

Methods: We evaluated 15-PDGH as a colon cancer susceptibility locus in a three-stage design. We first genotyped 102 single-nucleotide polymorphisms (SNPs) in the 15-PGDH gene, spanning ∼50 kb up and down-stream of the coding region, in 464 colon cancer cases and 393 population controls. We then genotyped the same SNPs, and also assayed the expression levels of 15-PGDH in colon tissues from 69 independent patients for whom colon tissue and paired germline DNA samples were available. In the final stage 3, we genotyped the 9 most promising SNPs from stages 1 and 2 in an independent sample of 525 cases and 816 controls (stage 3).

Results: In the first two stages, three SNPs (rs1365611, rs6844282 and rs2332897) were statistically significant (p<0.05) in combined analysis of association with risk of colon cancer and of association with 15-PGDH expression, after adjustment for multiple testing. For one additional SNP, rs2555639, the T allele showed increased cancer risk and decreased 15-PGDH expression, but just missed statistical significance (p-adjusted = 0.063). In stage 3, rs2555639 alone showed evidence of association with an odds ratio (TT compared to CC) of 1.50 (95% CI = 1.05-2.15, p = 0.026).

Conclusions: Our data suggest that the rs2555639 T allele is associated with increased risk of colon cancer, and that carriers of this risk allele exhibit decreased expression of 15-PGDH in the colon.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Schematic of HPGD gene, which encodes 15-PGDH, showing location of rs2555639.
Figure 2
Figure 2. Linkage Disequilibrium (LD) Plot of Genotyped SNPs.
LD plot of all SNPs selected for replication in all Caucasian samples. Values within boxes are correlations (R2).
See this image and copyright information in PMC

References

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