Polymorphisms in the precursor microRNAs and aflatoxin B1‐related hepatocellular carcinoma

Abstract

The altered expression of some microRNAs (miRNAs) is observed in hepatocellular carcinoma (HCC); however, the genetic polymorphisms in the precursor miRNAs (pre-miRNAs) in aflatoxin B1 (AFB1)-related HCC have not yet been investigated. A hospital-based case-control study, including 1,706 HCC cases and 2,270 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area of China to assess the relationship between 48 polymorphisms in the pre-miRNAs and AFB1-related HCC risk and prognosis. Among 48 polymorphisms, only rs28599926 (in the miRNA 1268a) affected HCC risk. Compared with the homozygote of rs28599926C alleles (rs28599926-CC), the genotypes of rs28599926 T alleles (namely rs28599926-CT or -TT) increased HCC risk (odds ratio [OR]: 1.63 and 5.52, 95% confidence interval [CI]: 1.40-1.90 and 4.27-7.14, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. This polymorphism was associated not only with larger tumor size, higher portal vein tumor risk, and tumor dedifferentiation, but also with higher AFB1 adducts levels and increasing the mutation risk of TP53 gene. Furthermore, rs28599926 modified the tumor recurrence-free survival (hazard ratio [HR]: 2.86, 95% CI: 2.36-3.43) and overall survival (HR: 2.12, 95% CI: 1.86-2.41) of cases. Additionally, one target of miR-1268a was show to be the ADAMTS4 mRNA and rs28599926 polymorphism might modify ADAMTS4 expression. These findings indicate that polymorphisms in the pre-miRNAs may be risk and prognostic biomarkers of AFB1-related HCC, and rs28599926 in miR-1268a is such a potential candidate. © 2015 Wiley Periodicals, Inc.

Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma

“…The level of miR-1268a expression in cancerous tissues was analyzed using our previously published TaqMan quantitative reverse transcription-PCR technique24. In this study, the relative amount of miR-1268 to internal control U6 was calculated as 2 −ΔCt method, where ΔCt = (Ct miR-1268a  − Ct U6 ).…”

“…Among these microRNAs, microRNA-1268a (miR-1268a), which is an important abundant microRNA encoded by MIR1268A gene and functionally involves in embryogenesis and cell differentiation23, is particular concern in our research projects. Our previous data from a large molecular epidemiological investigation have exhibited that the genetic variables in the seeding region of miR-1268a were correlated with tumor angiogenesis and may involve in the carcinogenesis of HCC24. This suggests a possible relationship between miR-1268a and the prognosis of HCC characterized by rich blood vessels.…”

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

“…The same research group found that miR-24, which has been reported to be an “oncomir” [103], was upregulated in liver tumors from patients who resided in regions with high AFB1 exposure [104]. Further, in a large case-control hospital study in China that investigated polymorphisms in pre-miRNAs as potential risk and prognostic biomarkers of AFB1-related HCC, rs28599926 in miR-1268a was identified as one such candidate [105]. …”

Hepatocellular carcinoma and the risk of occupational exposure

“…This could be caused by the aflatoxin ability to determine the mutation of the p53 tumor suppressor gene, which in normal conditions induces the apoptosis processes [74][75][76][77] . The risk of HCC increases when the exposure occurs in the presence of HBV infection, as occurs in the Chinese population [78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96] .…”