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Assessment of HER1 (rs11543848) and HER2 (rs1136201) polymorphism and their association with colorectal cancer susceptibility in Khyber Pakhtunkhwa, Pakistan

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Abstract

Background

Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region.

Methods

In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR.

Results

Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352).

Conclusion

In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results.

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Acknowledgements

The authors extend their appreciation to the Researchers Supporting Project number (RSP2023R191), King Saud University, Riyadh, Saudi Arabia.

Funding

There is no funding source to disclose. The authors their-self contributed for the study.

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Authors and Affiliations

  1. Institute of Biotechnology and Genetic Engineering (Health Division), The University of Agriculture Peshawar, Peshawar, Pakistan

    Asad Ullah, Najeeb Ullah Khan & Sidra Tul Muntaha

  2. School of Medicine, Jiangsu University, Zhejiang, China

    Bibi Maryam Khan

  3. Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar, Pakistan

    Samiullah Khan & Aakif Ullah Khan

  4. Zoology Department, College of Science, King Saud University, P.O. Box: 2455, Riyadh, 11451, Saudi Arabia

    Mikhlid H. Almutairi

  5. Centre for Applied Mathematics and Bioinformatics (CAMB), Gulf University for Science and Technology, Hawally, Kuwait

    Ijaz Ali

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  1. Asad Ullah
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  2. Bibi Maryam Khan
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  4. Sidra Tul Muntaha
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  5. Samiullah Khan
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  6. Aakif Ullah Khan
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  7. Mikhlid H. Almutairi
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  8. Ijaz Ali
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Contributions

NUK designed and supervised the study, AU did the experimental work and write the manuscript, BMK, STM, SK and AUK help in samples collection, data analysis and MHA, IA review the manuscript.

Corresponding author

Correspondence to Najeeb Ullah Khan.

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Conflicting interest

The author/s have no conflicting interest.

Ethical approval

This study was conducted at Institute of Biotechnology and Genetic Engineering (IBGE), under the ethical approval (No: IBGE/2022/013).

Consent to participate and publish

All the patients and healthy controls were individually briefed about the aim and objectives of the study, written consent was taken before taking their data and blood samples.

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Ullah, A., Khan, B.M., Khan, N.U. et al. Assessment of HER1 (rs11543848) and HER2 (rs1136201) polymorphism and their association with colorectal cancer susceptibility in Khyber Pakhtunkhwa, Pakistan. Mol Biol Rep 51, 1 (2024). https://doi.org/10.1007/s11033-023-08943-y

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