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Ethnic-specific associations between body mass index and gastric cancer: a Mendelian randomization study in European and Korean populations

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A Letter to the Editor to this article was published on 18 March 2024

Abstract

Background

Given the uncertainties surrounding the associations in previous epidemiological studies, we conducted linear and nonlinear Mendelian randomization (MR) studies to evaluate whether body mass index (BMI) associated with gastric cancer (GC) risk in European and Korean.

Methods

Genome-wide association study-summary statistics were used from the Pan-UK Biobank, the Genetic Investigation of Anthropometric Traits consortium, the K-CHIP consortium, and BioBank Japan. BMI-associated single nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs) in MR to identify the association between BMI and GC. Both linear and nonlinear MR analyses were performed. Sensitivity analyses were also conducted for individuals below or above a BMI of 24 kg/m2.

Results

The study used 22 and 55 SNPs as IVs for BMI in European and Korean populations, respectively. Genetically predicted BMI was positively associated with GC risk in the European population (Odds ratio per 1 kg/m2 increase; 95% CI = 1.17; 1.01–1.36 using simple median method), but no significant association was observed in the Korean population. However, the nonlinear MR identified a U-shaped association between BMI and GC in the Korean population, with both low and high BMIs associated with increased GC risk. A BMI of 24 kg/m2 presented the lowest risk. Sensitivity analyses did not yield any genome-wide significant SNPs.

Conclusion

While MR analysis suggests a linear association between BMI and GC in those of European ancestry, nonlinear MR hints at a U-shaped association in Koreans. This suggests the association between BMI and GC risk may vary according to ethnic ancestry.

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Data availability

The K-CHIP consortium genotype data are available upon request under the data sharing policy of the National Research Institute of Health, Korea (https://www.koreanchip.org/blank-8). Other data supporting our findings are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was conducted with bioresources from National Biobank of Korea, the Korea Disease Control and Prevention Agency, Republic of Korea (KBN-2022-056).

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (NRF-2016R1A2B4014552); the Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government (MSIT) (2020M3C9A5086234).

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Authors and Affiliations

  1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    Sangjun Lee & Sue K. Park

  2. Cancer Research Institute, Seoul National University, 103 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea

    Sangjun Lee & Sue K. Park

  3. Department of Biomedical Science, Seoul National University Graduate School, Seoul, Republic of Korea

    Sangjun Lee

  4. Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, Republic of Korea

    Sue K. Park

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Contributions

SL and SKP had the study conception and designed the study. SL analyzed the data. SL and SKP interpreted data. SL and SKP drafted the article. SKP revised the article critically for important intellectual content. All authors approved the final manuscript for submission.

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Correspondence to Sue K. Park.

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The authors declare that they have no conflict of interest.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. The Institutional Review Boards of Seoul National University Hospital (2211-119-1380) approved this study.

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Lee, S., Park, S.K. Ethnic-specific associations between body mass index and gastric cancer: a Mendelian randomization study in European and Korean populations. Gastric Cancer 27, 19–27 (2024). https://doi.org/10.1007/s10120-023-01439-5

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