Abstract
AimsCyclin dependent kinase 6 (CDK6) plays a crucial role in malignant tumor whereas less is reported in cervical cancer development. The aim of this study was to evaluate the effects of CDK6 3' untranslated region (3'UTR) polymorphisms on cervical cancer susceptibility among Uyghur females.MethodsThe genotypes of the six CDK6 variants (rs8179, rs42032, rs42033, rs42034, rs42035, and rs42038) were identified among 306 cervical cancer cases and 310 healthy controls with the Agena MassARRAY platform. The associations of the candidate single nucleotide polymorphisms (SNPs) with the cervical cancer risk were evaluated under genetic models using conditional logistic regression analysis. Bioinformatics analysis was performed for SNP function prediction with the online databases. The expression differences between tumor tissues and normal cervix samples were also examined by Real‐time PCR.Results CDK6 rs8179 and rs42033 were correlated to the decreased risk of cervical cancer in Uyghurs under the allele model (rs8179 and rs42033: OR = 0.60, 95% CI: 0.37–0.99, p = 0.043) and log‐additive model (rs8179 and rs42033: OR = 0.62, 95% CI: 0.38–1.00, p = 0.047). Rs8179, rs42032, and rs42033 were associated with susceptibility to high‐grade cervical cancer in different genetic models as well (p < 0.05). Dataset‐based analysis also uncovered the potential effects of these significant SNPs. In addition, aberrant expression of CDK6 were detected in cervical tumors.ConclusionsOur results suggested the relationships between CDK6 3'UTR polymorphisms and cervical cancer pathogenesis, and the involvement of CDK6 in cervical cancer development among Uyghur females.
Highlights
With a significant estimated incidence (570,000) and mortality (311,000) worldwide, cervical cancer ranks as the fourth most common cancer and the leading cause of cancer death in females (Bray et al, 2018)
Single nucleotide polymorphisms (SNPs): Single nucleotide polymorphism; OR: Odds ratio; 95% confidence intervals (CIs): 95% confidence interval
This study first demonstrated the relationships between the 3' untranslated region (3'UTR) variants in Cyclin dependent kinase 6 (CDK6) gene and cervical cancer susceptibility in Uyghur females from Xinjiang Uyghur Autonomous Region of China
Summary
With a significant estimated incidence (570,000) and mortality (311,000) worldwide, cervical cancer ranks as the fourth most common cancer and the leading cause of cancer death in females (Bray et al, 2018). Wang et al have provided the significant evidence of the influence of LINC00673 rs11655237 polymorphism on cervical cancer risk among Chinese females (Wang & Luo, 2018). These results strongly imply the genetic predisposition for individuals to cervical cancer and yield new insights on its pathogenesis. The aberrant activity of CDK6‐cyclin complex has been detected in hematopoietic malignancies (Scheicher et al, 2015) These results provide the evidence for the crucial role of CDK6 in cancer development and we could hypothesize that there might be some relationships between CDK6 and cervix oncogenesis. The in‐depth genetic information obtained from the findings could enhance our comprehension of the CDK6 in cervical cancer, but provide new targets for cancer assessment, prevention and prognosis in Uyghur population
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