Pri-miR-34b/c rs4938723 polymorphism contributes to acute lymphoblastic leukemia susceptibility in Chinese children

Abstract

A polymorphism rs4938723 (T > C) within the promoter region of pri-miR-34b/c has been found to not only affect the expression of mature miR-34b/c but also contribute to the susceptibility to several cancer types. We designed a case-control study to evaluate the role of rs4938723 in childhood acute lymphoblastic leukemia (ALL). The rs4938723 CC genotype was significantly associated with reduced ALL risk (p = 0.003, OR_adjusted = 0.51, 95% CI = 0.33–0.80 for CC vs. TT). Stratification analyses showed the differences were pronounced in older (> 6 years), male subjects, as well as in patients in low risk and T-ALL subtypes. The in vitro luciferase assays in Jurkat and K-562 cell lines showed that the transcription activity of miR-34b/c was increased when T allele transited to C allele (p < 0.05). In conclusion, rs4938723 genetic variant contributed to the susceptibility to Chinese childhood ALL by influencing the transcription activity of miR-34b/c promoter.

Keywords:

• childhood ALL
• genetic susceptibility
• miR-34b/c
• molecular epidemiology
• transcription activity

Acknowledgements

This study was partly supported by the National Natural Science Foundation of China (81202268, 81070436, and 81402749), Natural Science Foundation of Jiangsu Province (BK20131014 and BK2011775), Collaborative Innovation Center for Cancer Personalized Medicine and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2015.1092528.