Abstract
Abstract Purpose: Polymorphisms in the DNA repair genes JWA and XRCC1 have recently been reported to increase susceptibility for gastric cancer, but the expression pattern and significance of these genes in gastric cancer is unknown. Experimental Design: Expression of JWA and XRCC1 were assessed by immunohistochemistry in three independent tissue microarray sets of gastric carcinoma (total n=1227), and paired adjacent non-tumoral tissues (n=80) with minimum five years follow-up time. Prognostic value of JWA and XRCC1 and of clinicopathologic factors, were evaluated in patients treated only with surgery. The predictive role of JWA and XRCC1 expression status in cases treated with adjuvant chemotherapy compared with surgery alone was analyzed. Results: JWA and XRCC1 protein levels were significantly downregulated in gastric cancer lesions compared with adjacent non-cancerous tissues (P < 0.001 for all correlations). Low tumoral JWA or XRCC1 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients without adjuvant treatment. Multivariate regression analysis showed that low JWA and XRCC1 expression, separately and together, were independent negative markers of OS. Adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) significantly improved OS compared with surgery alone (log-rank test, P = 0.01), however, this effect was evident only in the JWA or XRCC1 low expression group (HR = 0.44; 95% CI = 0.26-0.73; P = 0.002, and HR = 0.44; 95% CI = 0.26-0.75; P = 0.002, respectively). Conclusions: JWA and XRCC1 protein expression in tumor are novel candidate prognostic markers and predictive factors for benefit from adjuvant FLO chemotherapy in resectable human gastric carcinoma. Acknowledgements: This study was supported in part by the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, the National Natural Science Foundation of China (30930080, 81001231), the Foundation of Cancer Center of Nanjing Medical University (08ZLKF08), and the Postdoctoral Science Foundation of China (20100481165). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3579. doi:1538-7445.AM2012-3579
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