Abstract

<div>Abstract<p><b>Purpose:</b> There is evidence that genetic variation in the prostaglandin pathway affects cancer susceptibility and progression. Conflicting data from several studies exist for the association of <i>PTGS2</i> (cyclooxygenase 2) polymorphisms with breast cancer risk. We investigated associations between common germ-line variations in seven genes in the prostaglandin pathway and breast cancer susceptibility and survival among women with invasive breast cancer in the SEARCH study.</p><p><b>Experimental Design:</b> DNA samples from 9,030 cases and controls were genotyped for 64 single nucleotide polymorphisms tagging known common variants (minor allele frequency > 0.05) in <i>PTGS1, PTGS2, TBXAS1, PTGIS, PTGES, PTGDS</i>, and <i>PGDS</i> with a two-stage case-control study design.</p><p><b>Results:</b> Four tagging single nucleotide polymorphisms showed modest association with breast cancer susceptibility. All four fit a recessive genetic model. Minor allele homozygotes for <i>PTGISrs5602</i> [odds ratio (OR), 1.15; 95% confidence interval (95% CI), 1.04-1.27; <i>P</i> = 0.005], <i>PTGISrs8183919</i> (OR, 1.22; 95% CI, 1.06-1.41; <i>P</i> = 0.006), and <i>TBXASrs41727</i> (OR, 1.83; 95% CI, 1.22-2.73; <i>P</i> = 0.003) are associated with an increased risk compared with common allele carriers. For <i>PTGISrs44627</i> minor allele homozygotes (OR, 0.66; 95% CI, 0.5-0.86; <i>P</i> = 0.002), a protective effect was observed.</p><p><b>Conclusion:</b> Specific <i>PTGIS</i> and <i>TBXAS1</i> variants may affect breast cancer susceptibility, but common variants in <i>PTGS1, PTGS2, PTGES, PTGDS</i>, and <i>PGDS</i> have no major role in breast cancer susceptibility. None of the variants in the seven genes studied appear to affect survival. Further larger studies correlating clinical and genotypic data are required to establish if the clinical utility of prostaglandin-targeted therapies, as chemoprevention agents, is influenced by an individual's profile of genetic variants in key prostaglandin pathway genes.</p></div>

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