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Promoter CpG island hypermethylation and down regulation of XRCC1 gene can augment in the gastric carcinogenesis events

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Abstract

Gastric cancer (GC) is a multistep process characterized by a gradual accumulation of genetic and epigenetic alterations in genes at various stages of progression. Epigenetic alterations like DNA methylation play an important role in cancer and may serve as a biomarker for cancer. The present study was aimed to investigate the promoter hypermethylation, expression profile, and Arg399Gln gene polymorphism of DNA repair gene XRCC1 (X-ray repair cross complimentary group I) in GC patients. A total of 60 histopathologically confirmed GC subjects were recruited in the study. Information on various dietary, lifestyle and environmental factors was obtained in face-to-face interviews using a structured questionnaire from each subject. Tissue samples were taken along with adjacent non-cancerous tissues for analysis. Promoter methylation status and expression of XRCC1 gene was evaluated using MS-PCR and western blotting respectively; while as Arg399Gln polymorphism was analyzed by PCR-RFLP. We found that the XRCC1 gene promoter of 38.3% cancerous tissues were methylated compared to 13.3% of adjacent normal tissues. The promoter hypermethylation status of the gene was found to be significantly associated with the loss of protein expression (P < 0.0001, OR = 14.63; 95% CI 4.01–53.43). However, we did not find any significant association of polymorphism of XRCC1 Arg399Gln with promoter methylation or protein expression. Further, comparison of methylation status and protein expression with clinical parameters like age, smoking status, etc. was also not significant (P > 0.05). The present study indicates that XRCC1 undergoes aberrant promoter hypermethylation with subsequent loss of protein expression in gastric cancer.

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Abbreviations

GC:

Gastric cancer

DNA:

Deoxyribonucleic acid

BER:

Base excision repair

PARP:

Poly ADP ribose polymerase

SNP:

Single nucleotide polymorphism

XRCC1:

X-ray repair cross complementary 1

PCR:

Polymerase chain reaction

EDTA:

Ethylenediaminetetraacetic acid

MS-PCR:

Methylation specific polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

CpG:

Cytosine-phosphate-guanine

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Acknowledgements

The authors acknowledge the financial support provided by the Council of Scientific and Industrial Research (CSIR), Pusa, New Delhi under the Reference Number: 09/251(0049)/2012-EMR-I. The authors are extremely thankful to all the subjects who took part in this study. We are also grateful to all the consultants and paramedical staff at SKIMS, Srinagar, for their valued help during subject recruitment and sample collection. The authors are also thankful to Dr. Iqra Hamid and Ms. Sumaiya Nabi, Department of Biochemistry, University of Kashmir for their help and research assistance during this work.

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Authors and Affiliations

  1. Department of Biochemistry, University of Kashmir, Srinagar, India

    Bushra Nissar

  2. Department of Gastroenterology, Government Medical College and Hospital, Srinagar, India

    Showkat A. Kadla

  3. Department of General Surgery, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India

    Khursheed Alam Wani

  4. Department of MRDG, Indian Institute of Science, Bangalore, India

    Idrees A. Shah

  5. Centre of Research for Development, University of Kashmir, Srinagar, India

    Bashir Ahmad Ganai

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  1. Bushra Nissar
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  2. Showkat A. Kadla
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Correspondence to Bashir Ahmad Ganai.

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The authors report no conflicts of interest.

Ethical approval

All the patients duly signed the informed consent and the recruitment of patients was initiated following the approval from the institutional ethics committee of Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, India vide reference number: SIMS 1 31/IEC-SKIMS/2014-01-03.

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Nissar, B., Kadla, S.A., Wani, K.A. et al. Promoter CpG island hypermethylation and down regulation of XRCC1 gene can augment in the gastric carcinogenesis events. Mol Biol Rep 48, 405–412 (2021). https://doi.org/10.1007/s11033-020-06064-4

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  • DOI: https://doi.org/10.1007/s11033-020-06064-4

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