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Interaction analysis of IL-12A and IL-12B polymorphisms with the risk of colorectal cancer

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Tumor Biology

Abstract

IL-12 is an antitumor cytokine with functions of inhibiting tumor growth, invasion, and metastasis, indicating that IL-12 is a promising candidate for cancer treatment. The aim of this study was to investigate the association of IL-12A rs568408, IL-12A rs2243115, and IL-12B rs3212227 with the susceptibility to colorectal cancer (CRC). Two hundred and fifty-seven histopathologically confirmed CRC patients and 236 age- and gender-matched controls were enrolled. The three polymorphisms were genotyped using a polymerase chain reaction–restriction fragment length polymorphism assay. We found that the IL-12A rs568408 AG/AA genotypes were associated with an increased risk of CRC with an adjusted odds ratio (OR) of 1.66 (95 % confidence interval (CI), 1.11–2.48). Stratified analyses showed that patients carrying the IL-12B rs3212227AC/CC genotypes had a 1.97-fold increased risk of tumor metastasis (OR = 1.97; 95 % CI, 1.04–3.70). Gene–gene interaction analysis showed that subjects carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AA genotypes had a 2.40-fold increased risk of CRC (OR = 2.40; 95 % CI, 1.14–5.07) and individuals carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AC/CC genotypes had a 1.93-fold increased risk of CRC (OR = 1.93; 95 % CI, 1.10–3.41). These findings indicate that IL-12A rs568408 and IL-12B rs3212227 may be related to the development of CRC.

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Funding

This study was funded by the National Natural Science Foundation of China (Nos. 81302149 and 81202387), the Ph.D. Programs Foundation of Ministry of Education of China (No. 20130181120011), Distinguished Young Scientist of Sichuan University (No. 2013SCU04A38), and the Science & Technology Pillar Program of Sichuan Province (Nos. 2014SZ0001 and 2013JY0013).

Conflicts of interest

None

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Correspondence to Linbo Gao or Lin Zhang.

Additional information

Ruifen Sun and Fu Jia contributed equally to this work.

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Sun, R., Jia, F., Liang, Y. et al. Interaction analysis of IL-12A and IL-12B polymorphisms with the risk of colorectal cancer. Tumor Biol. 36, 9295–9301 (2015). https://doi.org/10.1007/s13277-015-3685-7

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  • DOI: https://doi.org/10.1007/s13277-015-3685-7

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