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Association of RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies

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Abstract

The receptor for advanced glycation end products (RAGE), a member of immunoglobulin superfamily, has been proved to stimulate survival, growth, and metastatic spread of cancers cells. Evidence suggested that the 82G/S, −374T/A, and −429T/C polymorphisms in RAGE promoter region might affect the risk of cancer; however, data from epidemiological studies showed conflicting results that remain to be further clarified. This meta-analysis was performed to derive a more precise estimation of 82G/S, −374T/A, and −429T/C polymorphisms and risk of cancer. A comprehensive electronic search was conducted for articles published up until December 2, 2014, in Medline (PubMed), Embase, the Cochrane Library and Google Scholar. A total of 12 case–control articles were included in this meta-analysis, providing 3,374 cases and 3,757 controls for 82G/S, 2,936 cases and 3,338 controls for −374T/A, and 2,882 cases and 3,279 controls for −429T/C specifically. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the associations with risk of cancer. Overall, we observed significantly increased risk of cancer in relation to 82G/S (A vs. G: OR 1.321, 95 % CI 1.164–1.499, P het 0.028; AA vs. GG: OR 1.823, 95 % CI 1.541–2.157, P het < 0.001; AG vs. GG: OR 1.399, 95 % CI 1.120–1.746, P het 0.002; GA+AA vs. GG: OR 1.470, 95 % CI 1.187–1.821, P het 0.002; AA vs. GG+AG: OR 1.416, 95 % CI 1.158–1.732, P het 0.107) and reduced risk of cancer in relation to −374T/A (AA vs. TT: OR 0.818, 95 % CI 0.686–0.976, P het 0.025; A vs. T: OR 0.908, 95 % CI 0.840–0.981, P het 0.014). In subgroup analysis for 82G/S, a significantly elevated cancer risk was indicated in the population of Asian and patients with lung cancer, and for −374T/A, reduced risk was indicated in population of Caucasian and patients with lung cancer and breast cancer. But no significant association was observed between −429T/C and risk of cancer. Thus, this meta-analysis revealed that 82G/S polymorphism is associated with a significantly increased risk of cancer, while −374T/A polymorphism is associated with a reduced risk of cancers.

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Acknowledgments

This work was supported by the Natural Science Foundation of Jiangsu Province [Grant Number: BK2012482], National Natural Science Foundation of China [Grant Number: 81472702] and Jiangsu Provincial Special Program of Medical Science [Grant Number: BL2012030].

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The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, 210009, People’s Republic of China

      Wenjie Xia, Youtao Xu, Qixing Mao, Gaochao Dong, Run Shi, Jie Wang, YanYan Zheng, Lin Xu & Feng Jiang

    2. The Fourth Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China

      Wenjie Xia, Qixing Mao & Run Shi

    3. The First Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China

      Youtao Xu

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    Xia, W., Xu, Y., Mao, Q. et al. Association of RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies. Med Oncol 32, 33 (2015). https://doi.org/10.1007/s12032-014-0442-5

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