Abstract 122: Prospective study of urinary prostaglandin E2 and prostacyclin metabolites and lung cancer risk .

Abstract

Abstract Cumulative evidence from both in vitro and animal studies suggests that cyclooxygenase-2 (COX-2) may be involved in the development and progression of lung cancer. Overproduction of prostaglandin E synthase and prostaglandin E2 (PGE2), one of the end products of the COX-2 pathway, has been implicated in the pathogenesis of non-small cell lung cancer. On the other hand, evidence suggests that prostacyclin (PGI2), another end products of the COX-2 pathway, may differ from other bioactive prostaglandins and may exert cancer-inhibitory effects on the development of lung cancer. PGE2 is quickly converted to 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), a major PGE2 metabolite and excreted in urine. PGI2 is rapidly converted into 6-keto-PGF1a, a chemically stable but biologically inactive hydration product. Circulatory 6-keto-PGF1a undergoes ß-oxidation and appears in the urine as 2,3-dinor-6-keto-PGF1a (PGI-M), the primary breakdown product of PGI2. Urinary PGE-M and PGI-M are stable compounds and can be measured accurately and reliably with newly developed and validated LC-MS and GC-MS assays. In this study, we evaluated the association of pre-diagnostic urinary PGE-M and PGI-M levels with subsequent risk of developing lung cancer. We conducted a nested case-control study using resources of the Shanghai Men's Health Study, a prospective cohort study, in which 61,491 Chinese men aged 40-74 years were recruited from 2002 to 2006 and followed for up to 7 years. Urinary PGE-M and PGI-M in 349 incident lung cancer patients were compared to 349 matched controls. Overall, the geometric mean of baseline level of urinary PGE-M did not differ significantly between cases and controls. Compared with the lowest quartile, the risks (odds ratios, ORs) of developing lung cancer were non-significantly elevated (1.48, 95% CI=0.91-2.40 for the highest quartile). No dose-response relationship was evident. The baseline level of urinary PGI-M was more than 20% higher in cases than in controls. The ORs for developing lung cancer increased from 1.0 to 1.14 (95% CI=0.66-1.95), 1.45 (95% CI=0.86-2.45), and 1.70 (95% CI=0.99-2.92) across the quartiles of urinary PGI-M levels (P for trend=0.0056). Excluding 63 case-control pairs who were diagnosed with lung cancer within one year of follow-up did not change the associations for PGE-M and PGI-M. No interaction was found between PGE-M and PGI-M in relation to lung cancer risk. In summary, using data from a large prospective cohort study, we found that high levels of urinary PGI-M, and possibly PGE-M, were associated with subsequent risk of developing lung cancer. Our data suggest that high activity of the COX-2 pathway, rather than the prostaglandin E2 alone, may play a major role in lung cancer development. Further studies are needed to evaluate these two urinary markers as possible biomarkers for lung cancer risk assessment. Citation Format: Qiuyin Cai, Yong-Bing Xiang, Wanqing Wen, Ginger L. Milne, Hong-Lan Li, Jie Wu, Gong Yang, Jing Gao, Tsogzolmaa Dorjgochoo, Yu-Tang Gao, Wei Zheng, Xiao Ou Shu. Prospective study of urinary prostaglandin E2 and prostacyclin metabolites and lung cancer risk . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 122. doi:10.1158/1538-7445.AM2013-122