Prostaglandin E2 (PGE2) promotes colorectal carcinogenesis. controls. We measured urinary PGE-M using a liquid chromatographic/mass spectrometric assay. Compared with women in the lowest quartile of urinary PGE-M women in the highest quartile had a multivariate odds ratio(OR) of 1 1.40(95% confidence interval(CI) 0.92 for any adenoma; 0.91(95% CI 0.48 for low-risk adenoma (solitary adenoma <1cm in greatest diameter with tubular/unspecified histology); and 1.66(95%CI 1.04 for high-risk adenoma (adenoma ≥ Fulvestrant (Faslodex) 1cm in greatest diameter and/or tubulovillous villous or high grade dysplasia histology or multiple adenomas of any size or histology). Regular use of anti-inflammatory drugs (≥2 standard tablets of aspirin/NSAIDs per week) was associated with a significant reduction in adenoma risk (multivariate OR 0.61 CI 0.43 in women with high baseline PGE-M (quartiles 2-4) but not low PGE-M (quartile 1). Urinary PGE-M is associated with an increased risk of high-risk adenoma. Anti-inflammatory drugs appear to reduce adenoma risk among women with high but not low PGE-M. Urinary PGE-M may serve as a biomarker to define subsets of the population who may Fulvestrant (Faslodex) obtain differential chemopreventive benefit from anti-inflammatory drugs. = <0.001). Among controls there was no significant difference in levels of urinary PGE-M according to use of aspirin/NSAIDs at the time of urine collection (P=0.43). Table 1 Characteristics of Adenoma Cases and Endoscopy-negative Controls The Spearman correlation coefficients between urinary PGE-M and several lifestyle factors are presented in Table 2. PGE-M directly correlated with age BMI and smoking. Table 3 shows the association between urinary Rabbit polyclonal to EARS2. PGE-M and the risk of overall colorectal adenoma according to quartile categories determined by the distribution of PGE-M among controls. Compared to the women in the lowest quartile of urinary PGE-M the multivariate OR for any adenoma was 1.40 (95% CI 0.92 – 2.14) for women in the highest quartile (for linear trend = 0.26). Compared to the women in the lowest quartile of urinary PGE-M the multivariate OR for high-risk adenoma was 1.66 (95% CI 1.04 – 2.67) for women in the highest quartile (for linear trend = 0.04). However PGE-M level was not significantly associated with the low-risk adenoma (for linear trend = 0.30) (Table 3). We also used restricted cubic splines to examine the shape of the relationship between PGE-M levels and the risk of high-risk adenoma (Figure 1). A test for overall significance of the curve was p = 0.04 and the test for a nonlinear relation was p = 0.09. Figure 1 Restricted cubic spline plot for PGE-M and high-risk adenoma. Odds ratio of adenoma is plotted according to urinary PGE-M (ng/mg Cr.) Hatched lines represent 95% CIs. Spline was adjusted for the same factors as the multivariate model in Table 3. Table 2 Spearman correlation coefficients between urinary PGE-M and other lifestyle factors Table 3 Risk of adenoma according to urinary PGE-M We also conducted analyses according to subtypes of adenoma defined by histology size or number (Supplementary Table 1). Compared with women in the lowest quartile of urinary PGE-M women in the highest quartile had a multivariate ORs of 1 1.65 Fulvestrant (Faslodex) (95% CI 1.02 for adenoma with advanced histology (tubulovillous villous or high-grade dysplasia); Fulvestrant (Faslodex) 1.69 (95% CI 1 for large adenoma (≥ 1 cm in greatest diameter) and 2.26 (95% CI 1.25 for multiple (≥ 2) adenoma. In contrast PGE-M level was not significantly Fulvestrant (Faslodex) associated with early histology (tubular/unspecified) small (< 1cm in greatest diameter) or solitary adenoma. We also examined the association of urinary PGE-M and risk of high-risk adenoma according to strata of selected lifestyle factors associated with adenoma risk (Table 4). Fulvestrant (Faslodex) The association between PGE-M and high risk adenoma did not appear to vary according to subgroups defined by regular use of aspirin or NSAID calcium intake smoking status or body-mass index (P for interaction > 0.05 for all factors). Table 4 Risk of high-risk adenoma according to urinary PGE-M stratified by other risk factors Based on the shape.