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Investigating the association between rs6983267 polymorphism and susceptibility to gastrointestinal cancers in Iranian population

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Abstract

Genome-wide association studies have revealed that some single nucleotide polymorphisms at 8q24, such as rs6983267, might be effective in susceptibility to various cancers in different populations. Therefore, rs6983267 might be useful as a marker for multiple cancers. In this study, we considered a population, including 478 gastrointestinal cancer cases from the Iranian population, to investigate the association between rs6983267 and susceptibility to gastrointestinal cancers. The samples were genotyped using the TaqMan real-time PCR method while 10% of them were also confirmed by sequencing. Higher frequency of G allele was associated with higher grades of tumors in esophageal cancer and the tumors located in the lower portion of the esophagus (OR 3.56; 95% CI 1.13–11.24; P = 0.03) and cardia (OR 5.24; 95% CI 1.26–21.83; P = 0.02), which both locations are involved in esophageal adenocarcinomas with poor prognosis. The results indicated that in the male subgroup, the rs6983267 GG genotype significantly enhanced the gastric cancer susceptibility (OR 4.76; 95% CI 1.57–14.45; P = 0.01). GG genotype also increased the risk of intestinal-type gastric cancer, located in non-cardia (OR 4.62; 95% CI 1.25–17.04; P = 0.02). Moreover, gastric cancer cases and controls with a family history of gastrointestinal tumors were mostly genotyped with the G allele (OR 3.61; 95% CI = 1.09–12.01; P = 0.04). There were no remarkable associations between rs6983267 and susceptibility to esophageal and colon cancers in the Iranian population. However, different genotypes of rs6983267 had significant correlations with tumor grade, cancer type, and family history of gastrointestinal cancers. Further investigations in a larger population and other ethnicities are required to confirm these results.

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Acknowledgements

This work was supported by Ferdowsi University of Mashhad (Grant Numbers: 46877, 46879, and 46673) and Mashhad University of Medical Sciences (Grant Number: 960032). We are indebted to our study participants, whose contribution made this research possible. We also thank all the clinicians and staff of Imam Reza Hospital, Isar Clinic, Reza Radiotherapy and Oncology Center, Omid Hospital, Ghaem Hospital, and Shahid Hashemi Nejad Hospital for their generous help in providing blood samples. The technical help of Mr. Mahdi Nohtani is also greatly appreciated.

Funding

This work was supported by Ferdowsi University of Mashhad (Grant Numbers: 46877, 46879, and 46673) and Mashhad University of Medical Sciences (Grant Number: 960032).

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Author notes

  1. Farzaneh Karimi and Seyedeh Mina Amiri-Moghaddam have contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Farzaneh Karimi, Seyedeh Mina Amiri-Moghaddam, Zakieh Bagheri, Ahmad Reza Bahrami & Maryam M. Matin

  2. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Ahmad Reza Bahrami & Maryam M. Matin

  3. Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Ladan Goshayeshi

  4. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Ladan Goshayeshi

  5. Hematology and Oncology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Abolghasem Allahyari, Alireza Bari & Hossein Rahimi

  6. Reza Radiotherapy and Oncology Center, Mashhad, Iran

    Marjane Mirsadraee

  7. Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Azar Fanipakdel & Ali Emadi-Torghabeh

  8. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Amin Kerachian

  9. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Amin Kerachian

  10. Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran

    Mohammad Amin Kerachian

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  1. Farzaneh Karimi
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Contributions

MMM and ARB designed the experiments and proofread the manuscript. FK, SMAM, and ZB performed the experiments and analyzed the data. FK and SMAM also wrote the manuscript. MMM and LG financially supported this project. LG, AA, MM, AFP, AB, AET, MAK, and HR helped in providing blood samples.

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Correspondence to Maryam M. Matin.

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Karimi, F., Amiri-Moghaddam, S.M., Bagheri, Z. et al. Investigating the association between rs6983267 polymorphism and susceptibility to gastrointestinal cancers in Iranian population. Mol Biol Rep 48, 2273–2284 (2021). https://doi.org/10.1007/s11033-021-06249-5

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