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Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study

  • Authors:
    • Dongsong Jia
    • Liping Lai
    • Fanyuan Li
    • Hong Wang
    • Shanrong Shu
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Gynecology and Obstetrics, Guangzhou Nansha District Maternal and Child Health Hospital, , Guangzhou, Guangdong 511466, P.R. China
    Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 8
    |
    Published online on: November 26, 2025
       https://doi.org/10.3892/ije.2025.31
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Abstract

Ovarian cancer is a fatal gynecological malignancy, which leads to a high mortality rate due to its late diagnosis. Methyltransferase‑like 3 (METTL3) gene polymorphisms play a crucial role in a number of malignant tumors. However, the effects of METTL3 polymorphisms on ovarian cancer susceptibility have rarely been reported, at least to the best of our knowledge. Thus, the present study aimed to determine the role of METTL3 polymorphisms in ovarian cancer. For this purpose, a three‑center case‑control study was conducted. Of note, four METTL3 gene polymorphisms (rs1263801G>C, rs1139130 G>A, rs1061027 C>A and rs1061026 T>G) were genotyped using TaqMan quantitative‑polymerase chain reaction assay in 244 patients with ovarian cancer and 276 controls. Odds ratios and 95% confidence intervals were used as indicators to assess relation. The results revealed that the rs1263801 CC genotype was a protective factor for ovarian cancer; stratified analysis revealed that the CC genotype reduced susceptibility to ovarian cancer compared to the GG/GC genotype in women aged >51 years. The rs1061027 CA/AA genotype reduced susceptibility compared with the CC genotype. In the stratified analysis, the rs1061027 C>A mutation was a protective factor in women <51 years of age, without metastasis, clinical stage III disease, those who had been pregnant more than three times, post‑menopause, with a high expression of estrogen receptor, p16, progesterone receptor, paired box 8 and WT1, and a low expression of p16 and Ki‑67, wild‑type p53‑negative and mutant p53‑positive. The rs1061026 TG genotype reduced susceptibility to ovarian cancer, compared with the TT genotype; the TG/GG genotype was a protective factor and decreased susceptibility in women with clinical stage I disease, post‑menopause, with a low expression of Ki‑67, those who were wild‑type p53‑negative and mutant p53‑negative. The effects of the aforementioned three genetic polymorphisms on ovarian cancer susceptibility were independent. The rs1139130 G>A variation was not associated with susceptibility to ovarian cancer. Haplotype analysis revealed a reduced risk of developing ovarian cancer in haplotype CAT and haplotype CAG compared with haplotype GCT. On the whole, the present study demonstrates that METTL3 rs1263801 G>C, rs1061027 C>A and rs1061026 T>G polymorphisms are associated with a reduced susceptibility to ovarian cancer.
View Figures

Figure 1

Interaction diagram for the risk of
developing ovarian cancer. The interaction model describes the
percentage of entropy (information gain) explained by the two-way
interaction of each factor. Positive entropy indicates synergistic
or non-additive relationships (plotted in yellow), while negative
entropy indicates independent or additive (redundancy)
relationships (plotted in blue).

Figure 2

Functional implication of the
rs1061027 polymorphism in the METTL3 gene in breast tissue. The
expression of rs1061027 genotype and WTAP gene in breast tissue was
studied based on the public database GTEx portal. GTEx, Gene-Tissue
Expression.
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Spandidos Publications style
Jia D, Lai L, Li F, Wang H and Shu S: Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study. Int J Epigen 5: 8, 2025.
APA
Jia, D., Lai, L., Li, F., Wang, H., & Shu, S. (2025). Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study. International Journal of Epigenetics, 5, 8. https://doi.org/10.3892/ije.2025.31
MLA
Jia, D., Lai, L., Li, F., Wang, H., Shu, S."Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study". International Journal of Epigenetics 5.1 (2025): 8.
Chicago
Jia, D., Lai, L., Li, F., Wang, H., Shu, S."Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study". International Journal of Epigenetics 5, no. 1 (2025): 8. https://doi.org/10.3892/ije.2025.31
Copy and paste a formatted citation
x
Spandidos Publications style
Jia D, Lai L, Li F, Wang H and Shu S: Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study. Int J Epigen 5: 8, 2025.
APA
Jia, D., Lai, L., Li, F., Wang, H., & Shu, S. (2025). Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study. International Journal of Epigenetics, 5, 8. https://doi.org/10.3892/ije.2025.31
MLA
Jia, D., Lai, L., Li, F., Wang, H., Shu, S."Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study". International Journal of Epigenetics 5.1 (2025): 8.
Chicago
Jia, D., Lai, L., Li, F., Wang, H., Shu, S."Polymorphisms of METTL3 gene and ovarian cancer susceptibility: A three‑center case‑control study". International Journal of Epigenetics 5, no. 1 (2025): 8. https://doi.org/10.3892/ije.2025.31
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