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Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer

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Abstract

Background

The incidence of gastric cancer has long been at a high level in China, seriously affecting the health of Chinese people.

Aims

This case‒control study was performed to identify gene methylation biomarkers of gastric cancer susceptibility.

Methods

A total of 393 gastric cancer cases and 397 controls were included in this study. Gene methylation in peripheral blood leukocytes was detected by a methylation-sensitive high-resolution melting method, and the Helicobacter pylori antibody presence was semi-quantified in serum by ELISA.

Results

Individuals with total methylation of CDKN2B/P15 had a 1.883-fold (95%CI: 1.166–3.040, P = 0.010) risk of gastric cancer compared with unmethylated individuals. Individuals with both CDKN2B/P15 and NEUROG1 methylation had a higher risk of gastric cancer (OR = 2.147, 95% CI: 1.137–4.073, P = 0.019). The interaction between CDKN2B/P15 and NEUROG1 total methylation on gastric cancer risk was affected by the pattern of adjustment. In addition, the joint effects between CDKN2B/P15 total methylation and environmental factors, such as freshwater fish intake (OR = 6.403, 95% CI = 2.970–13.802, P < 0.001), irregular diet (OR = 5.186, 95% CI = 2.559–10.510, P < 0.001), unsanitary water intake (OR = 2.238, 95% CI = 1.144–4.378, P = 0.019), smoking (OR = 2.421, 95% CI = 1.456–4.026, P = 0.001), alcohol consumption(OR = 2.163, 95% CI = 1.309–3.576, P = 0.003), and garlic intake(OR = 0.373, 95% CI = 0.196–0.709, P = 0.003) on GC risk were observed, respectively. However, CDKN2B/P15 and NEUROG1 total methylation were not associated with gastric cancer prognosis.

Conclusion

CDKN2B/P15 methylation in peripheral blood may be a potential biomarker for evaluating susceptibility to gastric cancer. The joint effects between CDKN2B/P15 methylation and environmental factors may also contribute to gastric cancer susceptibility.

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Funding

This study was supported by grants from the Heilongjiang Provincial Natural Science Foundation of China (LH2020H020).

Author information

Author notes

  1. Haibo Zhou, Chuang Nie, and Wenjing Tian have contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, College of Public Health, Harbin Medical University, 197 Xuefu Road, Harbin, 150081, Heilongjiang Province, People’s Republic of China

    Haibo Zhou, Chuang Nie, Wenjing Tian, Xu Han, Jing Wang, Xinyu Du, Qi Wang, Xiaojie Zhu, Guanghui Xiang & Yashuang Zhao

Authors
  1. Haibo Zhou
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  2. Chuang Nie
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  3. Wenjing Tian
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  4. Xu Han
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  7. Qi Wang
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Contributions

XH, JW, and XD processed data and performed the analyses. QW, XZ, and GX prepared all the tables and figures. HZ, CN, WT, and YZ conceived, designed, and wrote the manuscript. All authors approved the final manuscript.

Corresponding author

Correspondence to Yashuang Zhao.

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All authors declare that they have no conflict of interest.

Ethical approval

The medical ethics involved in this study are consistent with the Declaration of Helsinki.

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All participants included in this study signed informed consent.

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Zhou, H., Nie, C., Tian, W. et al. Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer. Dig Dis Sci 68, 3009–3017 (2023). https://doi.org/10.1007/s10620-023-07917-1

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  • DOI: https://doi.org/10.1007/s10620-023-07917-1

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