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Evaluation of SNPs associated with mammographic density in European women with mammographic density in Asian women from South-East Asia

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Mammographic density (MD), after accounting for age and body mass index (BMI), is a strong heritable risk factor for breast cancer. Genome-wide association studies (GWAS) have identified 64 SNPs in 55 independent loci associated with MD in women of European ancestry. Their associations with MD in Asian women, however, are largely unknown.

Method

Using linear regression adjusting for age, BMI, and ancestry-informative principal components, we evaluated the associations of previously reported MD-associated SNPs with MD in a multi-ethnic cohort of Asian ancestry. Area and volumetric mammographic densities were determined using STRATUS (N = 2450) and Volpara™ (N = 2257). We also assessed the associations of these SNPs with breast cancer risk in an Asian population of 14,570 cases and 80,870 controls.

Results

Of the 61 SNPs available in our data, 21 were associated with MD at a nominal threshold of P value < 0.05, all in consistent directions with those reported in European ancestry populations. Of the remaining 40 variants with a P-value of association > 0.05, 29 variants showed consistent directions of association as those previously reported. We found that nine of the 21 MD-associated SNPs in this study were also associated with breast cancer risk in Asian women (P < 0.05), seven of which showed a direction of associations that was consistent with that reported for MD.

Conclusion

Our study confirms the associations of 21 SNPs (19/55 or 34.5% out of all known MD loci identified in women of European ancestry) with area and/or volumetric densities in Asian women, and further supports the evidence of a shared genetic basis through common genetic variants for MD and breast cancer risk.

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Data availability

The BioBank Japan dataset used in this manuscript is publicly available. All other genotype and phenotype datasets used to support the findings in this manuscript are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank all study participants and for their participation, and the radiologists, radiographers, support staff and research assistants of Subang Jaya Medical Centre, University Malaya Medical Centre and Cancer Research Malaysia for their contribution and support throughout the duration of this study. The Malaysian Mammographic Density Study and the Malaysian Breast Cancer Genetic Study was supported by grants from Newton-Ungku Omar Fund (Grant No: MR/P012930/1), Wellcome Trust (Grant No: v203477/Z/16/Z), Malaysian Ministry of Higher Education High Impact Research Grant (Grant No.: UM.C/HIR/ MOHE/06), and donations from the Sime Darby LPGA Tournament, Estee Lauder Group of Companies, Yayasan Sime Darby, Yayasan PETRONAS, and other donors of Cancer Research Malaysia. SGBCC is funded by NUS Start Up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant (Grant No: MRC/CG/NCIS/2010, NMRC/CG/012/2013, CGAug16M005, CG21APR1005), NMRC Clinical Scientist Award (Grant No: NMRC/CSA/0048/2013), NMRC Clinician Scientist Award-Senior Investigator (Grant No: NMRC/CSA-SI/0015/2017), Asian Breast Cancer Research Fund, Breast Cancer Prevention Programme under Saw Swee Hock School of Public Health, and Breast Cancer Screening and Prevention Programme under Yong Loo Lin School of Medicine. WKH and SM are recipients of the L’Oreal-UNESCO For Women in Science National Fellowship, SM is a recipient of the Ong Hin Tiang and Ong Sek Pek Foundation Postgraduate Scholarship, and JL is the recipient of a National Research Foundation Singapore Fellowship (NRF-NRFF2017-02) and supported by the Agency for Science, Technology and Research (A*STAR). SL was supported by CA244670 from the National Institute of Health.

Author information

Authors and Affiliations

  1. Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia

    Shivaani Mariapun, Weang Kee Ho, Mei Chee Tai & Soo-Hwang Teo

  2. School of Mathematical Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih, Selangor, Malaysia

    Shivaani Mariapun & Weang Kee Ho

  3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Mikael Eriksson & Per Hall

  4. Faculty of Medicine, University Malaya Cancer Research Institute, University Malaya, Kuala Lumpur, Malaysia

    Nur Aishah Mohd Taib, Kartini Rahmat & Soo-Hwang Teo

  5. Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

    Nur Aishah Mohd Taib & Cheng Har Yip

  6. Subang Jaya Medical Centre, Subang Jaya, Malaysia

    Cheng Har Yip

  7. Biomedical Imaging Department, Faculty of Medicine, Universiti Malaya Research Imaging Centre, University of Malaya, Kuala Lumpur, Malaysia

    Kartini Rahmat

  8. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore

    Jingmei Li & Mikael Hartman

  9. Human Genetics, Genome Institute of Singapore, Singapore, Singapore

    Jingmei Li

  10. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore

    Mikael Hartman

  11. Department of Surgery, National University Hospital and National University Health System, Singapore, Singapore

    Mikael Hartman

  12. Department of Oncology, Södersjukhuset, Stockholm, Sweden

    Per Hall

  13. Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK

    Douglas F. Easton

  14. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Sara Lindstrom

  15. Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Sara Lindstrom

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  1. Shivaani Mariapun
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  2. Weang Kee Ho
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  4. Mei Chee Tai
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  13. Soo-Hwang Teo
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Contributions

Conceptualization and design: SM, WKH and ST; Data collection: SM, NAMT, CHY, KR, JL and MH; Data analysis and interpretation: SM, WKH, ME, MCT, PH, DFE, SL and ST; Manuscript writing: SM, WKH, SL and ST; Reviewed and approved final version of manuscript: SM, WKH, ME, MCT, NAMT, CHY, KR, JL, MH, PH, DFE, SL and ST.

Corresponding author

Correspondence to Soo-Hwang Teo.

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Competing interests

The Authors declare no Competing Non-Financial Interests but the following Competing Financial Interests: Mikael Eriksson and Per Hall report research grants and a patent on system and method for assessing breast cancer risk using imagery with a license to iCAD, Inc.

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Mariapun, S., Ho, W.K., Eriksson, M. et al. Evaluation of SNPs associated with mammographic density in European women with mammographic density in Asian women from South-East Asia. Breast Cancer Res Treat 201, 237–245 (2023). https://doi.org/10.1007/s10549-023-06984-2

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