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Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer

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Abstract

Thyroid cancer is the most common malignancy of the endocrine glands, and during last couple of decades, its incidence has risen alarmingly, across the globe. Etiology of thyroid cancer is still debatable. There are a few worth mentioning risk factors which contribute to initiation of abnormalities in thyroid gland leading to cancer. Genetic instability is major risk factors in thyroid carcinogenesis. Among the genetic factors, the Src family of genes (Src, Yes1, Fyn and Lyn) have been implicated in many cancers but there is little data regarding the association of these (Src, Yes1, Fyn and Lyn) genes with thyroid carcinogenesis. Fyn and Lyn genes of Src family found engaged in proliferation, migration, invasion, angiogenesis, and metastasis in different cancers. This study was planned to examine the effect of Fyn and Lyn SNPs on thyroid cancer risk in Pakistani population in 500 patients and 500 controls. Three polymorphisms of Fyn gene (rs6916861, rs2182644 and rs12910) and three polymorphisms of Lyn gene (rs2668011, rs45587541 and rs45489500) were analyzed using Tetra-primer ARMS-PCR followed by DNA sequencing. SNP rs6916861 of Fyn gene mutant genotype (CC) showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs2182644 of Fyn gene, mutant genotype (AA) indicated statistically significant 17-fold increased risk of thyroid cancer (P < 0.0001). Statistically significant threefold increased risk of thyroid cancer was observed in genotype AC (P < 0.0001) of Fyn gene polymorphism rs12910. In SNP rs2668011 of Lyn gene, TT genotype showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs45587541 of Lyn gene, GA genotypes showed statistically significant 11-fold increased risk in thyroid cancer (P < 0.0001). Haplotype analysis revealed that AAATAG*, AGACAG*, AGCCAA*, AGCCAG*, CAATAG*, CGCCAG* and CGCCGA* haplotypes of Fyn and Lyn polymorphisms are associated with increased thyroid cancer risk. These results showed that genotypes and allele distribution of Fyn and Lyn are significantly linked with increased thyroid cancer risk and could be genetic adjuster for said disease.

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Acknowledgements

The authors acknowledge financial and infrastructural help from Higher Education Commission of Pakistan (HEC) and COMSATS University, Islamabad. The authors are thankful to patients and staff of Nuclear Medicine Oncology and Radiotherapy Institute (NORI), Islamabad, for contribution in this research.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad, Park Road Tarlai Kalan, Islamabad, Pakistan

    Asif Nisar, Mahmood Akhtar Kayani, Azhar Mehmood, Malik Waqar Ahmed, Aamir Parvez & Ishrat Mahjabeen

  2. Department of Radiation, Nuclear Oncology Radiation Institute, Islamabad, Pakistan

    Wajiha Nasir

  3. Pakistan Institute of Rehabilitation Sciences (PIRS), Isra University Islamabad Campus, Islamabad, Pakistan

    Malik Waqar Ahmed

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  1. Asif Nisar
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Contributions

All the authors contributed to the study conception and design. Material preparation and data collection were performed by [Asif Nisar], [Wajiha Nasir] and [Aamir Pervaz]. Experimentation and analysis were performed by [Asif Nisar], [Azhar Mehmood] and [Malik Waqar Ahmed]. The first draft of the manuscript was written by [Mahmood Akhtar Kayani] and [Ishrat Mahjabeen], and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Ishrat Mahjabeen.

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Present study was conducted after the prior approval by the Ethical Review Committee of the COMSATS University Islamabad and collaborating hospitals. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Communicated by Shuhua Xu.

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Nisar, A., Kayani, M.A., Nasir, W. et al. Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer. Mol Genet Genomics 297, 1649–1659 (2022). https://doi.org/10.1007/s00438-022-01946-7

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