Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.684941
Keywords
oral squamous cell carcinoma; MALAT1; single-nucleotide polymorphisms; susceptibility; progression
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Funding
- Wan Fang Hospital, Taipei Medical University [110-wf-swf-06, 110-wf-phd-03]
- TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program by Ministry of Education in Taiwan
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The study found that the rs3200401 T allele of the MALAT1 gene reduces the risk of oral squamous cell carcinoma (OSCC) and increases the risk of moderately/poorly differentiated OSCC. In individuals exposed to carcinogens, those carrying the rs3200401 T allele were more likely to develop high-grade OSCC. The rs619586 AG/GG genotype was also associated with increased risks of developing advanced stages and larger tumor sizes.
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, and long non-coding (Inc)RNA of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was recently reported to play a crucial role in OSCC development and progression. However, potential effects of genetic variants of MALAT1 on the development of OSCC are still unclear. Herein, we performed a case-control study in 1350 patients with OSCC and 1199 healthy controls to evaluate the association between functional single-nucleotide polymorphisms (SNPs) of MALAT1 and OSCC susceptibility, as well as its clinicopathologic characteristics. A TaqMan allelic discrimination assay was used to genotype four tagging SNPs, viz., rs3200401 C>T, rs619586 A>G, rs1194338 C>A, and rs7927113 G>A, and results showed that the MALAT1 rs3200401 T allele had a lower risk of OSCC (adjusted odds ratio (AOR): 0.779, 95% confidence interval (CI): 0.632 similar to 0.960, p=0.019) and a higher risk of developing moderately (grade ID/poorly (grade III) differentiated OSCC (AOR: 1.508-fold, 95% CI: 1.049 similar to 2.169, p=0.027) under a dominant model. According to environmental carcinogen exposure, patients with a betel quid-chewing habit who carried the T allele of rs3200401 more easily developed high-grade (II/III) OSCC (AOR: 1.588, 95% CI: 1.055 similar to 2.390, p=0.027), and patients with the same genotype but who did not chew betel quid had a lower risk of developing lymph node metastasis (AOR: 0.437, 95% CI: 0.255 similar to 0.749, p=0.003). In addition to rs3200401, the rs619586 AG/GG genotype was associated with increased risks of developing advanced stages (III+IV) and larger tumor sizes (>T2) compared to the M genotype, especially in the subgroup of betel quid chewers. Furthermore, analyses of clinical datasets revealed that the MALAT1 expression level was upregulated in OSCC compared to normal tissues, especially in the betel quid-chewing population. These results indicated involvement of MALAT1 SNPs rs3200401 and rs619586 in the development of OSCC and support the interaction between MALAT1 gene polymorphisms and the environmental carcinogen as a predisposing factor for OSCC progression.
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