SMAD2 rs4940086 heterozygosity increases the risk of cervical cancer development among the women in Bangladesh

Abstract

SMAD2 is a critical signal transducer molecule in the TGFβ- SMAD pathway which is also known for its tumor suppressor role. Genetic variations in SMAD2 render cells insensitive to its anti-proliferative signals leading to tumor formation. In this study, we demonstrate the impact of single nucleotide polymorphisms (SNPs) of SMAD2 (rs4940086 and rs8085335) on cervical cancer risk development in Bangladeshi population. 132 cervical cancer patients and 98 control volunteers were enrolled in the study and genotyped utilizing polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. The association between cervical cancer susceptibility and the chosen SNPs were evaluated through multiple logistic regression. SMAD2 rs4940086 heterozygous genotype (T/C) was associated with a 3.89 times higher risk of cervical cancer development (P = 0.001, AOR 3.89, 95% CI 1.777–8.513). The T/C and C/C genotypes in combination also significantly elevated cervical cancer risk (P = 0.035, AOR 1.876, 95% CI 1.047–3.364). Urban cancer patients had a significantly higher chance of carrying the rs4940086 polymorphism as compared to rural cancer patients (P = 0.045, OR 2.59 95% CI 1.02–6.59). SMAD2 rs8085335 heterozygous variant (A/G) demonstrated modest effects in increasing cervical cancer susceptibility (P = 0.594, AOR 1.247, 95% CI 0.554–2.809). Our results suggest that polymorphic variations in SMAD2, particularly rs4940086, can potentially elevate cervical cancer susceptibility in Bangladeshi women.

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Contributions

PSH: performed all the experiments and drafted the manuscript; MNHA: conceived research design, performed statistical analyses, drafted and revised the manuscript; NAN, FI: assisted in experiments, revised manuscript; MRI: revised manuscript; AH: conceptualized the research; MSI: principal investigator.

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Correspondence to Mohd Nazmul Hasan Apu.

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The authors disclose no competing interests.

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The current study was in accordance with the declaration of Helsinki and its further amendments and the ethical committee of the participating hospital approved the study protocol.

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Each patient and control subject signed an informed consent document after they were informed of the study objectives.

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Haque, P.S., Apu, M.N.H., Nahid, N.A. et al. SMAD2 rs4940086 heterozygosity increases the risk of cervical cancer development among the women in Bangladesh. Mol Biol Rep (2020). https://doi.org/10.1007/s11033-020-05572-7

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Keywords

  • Cervical cancer
  • Polymorphism
  • SMAD2
  • Risk