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

Xi-Dai Long1,2, Xiao-Ying Huang1, Jin-Guang Yao1

  • 1Department of Pathology, The Affiliated Hospital of Youjiang Medical College for Nationalities (AHYMCN), Baise, China.

Molecular Carcinogenesis
|July 9, 2015
PubMed

Insights

Genetic variations in precursor microRNAs (pre-miRNAs) are linked to aflatoxin B1-related liver cancer (HCC) risk and prognosis. Specifically, rs28599926 in miRNA 1268a is a significant biomarker for HCC development and patient survival.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Altered microRNA (miRNA) expression is implicated in hepatocellular carcinoma (HCC).
  • Genetic polymorphisms in precursor miRNAs (pre-miRNAs) and their role in aflatoxin B1 (AFB1)-related HCC remain unexplored.
  • AFB1 is a known carcinogen contributing to HCC development.

Purpose of the Study:

  • To investigate the association between pre-miRNA genetic polymorphisms and the risk and prognosis of AFB1-related HCC.
  • To identify specific pre-miRNA polymorphisms that influence HCC development and patient outcomes in high-AFB1 exposure populations.

Main Methods:

  • A hospital-based case-control study involving 1,706 HCC cases and 2,270 controls from a high AFB1 exposure region in China.
  • Genotyping of 48 polymorphisms in pre-miRNAs.
  • Statistical analysis to assess the relationship between polymorphisms, HCC risk, prognosis, AFB1 exposure, and TP53 mutations.

Main Results:

  • The rs28599926 polymorphism in miRNA 1268a was significantly associated with increased HCC risk (ORs 1.63-5.52).
  • Risk genotypes of rs28599926 interacted with AFB1 exposure and were linked to larger tumor size, higher portal vein invasion, tumor dedifferentiation, increased AFB1 adducts, and TP53 mutations.
  • rs28599926 significantly impacted tumor recurrence-free survival (HR: 2.86) and overall survival (HR: 2.12).
  • ADAMTS4 mRNA was identified as a target of miR-1268a, with potential modification of ADAMTS4 expression by the rs28599926 polymorphism.

Conclusions:

  • Pre-miRNA polymorphisms, particularly rs28599926 in miR-1268a, may serve as valuable biomarkers for predicting AFB1-related HCC risk and prognosis.
  • The rs28599926 polymorphism influences HCC development, progression, and patient survival, potentially through modulation of ADAMTS4 expression.
Keywords:
aflatoxin B1hepatocellular carcinomamiR-1268apolymorphismpre-miRNA

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