Relevance of the MHC region for breast cancer susceptibility in Asians

Relevance of the MHC region for breast cancer susceptibility in Asians

Breast Cancer

10.1007/s12282-022-01366-w

http://dx.doi.org/10.1007/s12282-022-01366-w

Peh Joo Ho, Alexis Jiaying Khng, Benita Kiat-Tee Tan, Ern Yu Tan, Su-Ming Tan, Veronique Kiak Mien Tan, Geok Hoon Lim, Kristan J. Aronson, Tsun L. Chan, Ji-Yeob Choi, Joe Dennis, Weang-Kee Ho, Ming-Feng Hou, Hidemi Ito, Motoki Iwasaki, Esther M. John, Daehee Kang, Sung-Won Kim, Allison W. Kurian, Ava Kwong, Artitaya Lophatananon, Keitaro Matsuo, Nur Aishah Mohd-Taib, Kenneth Muir, Rachel A. Murphy, Sue K. Park, Chen-Yang Shen, Xiao-ou Shu, Soo Hwang Teo, Qin Wang, Taiki Yamaji, Wei Zheng, Manjeet K. Bolla, Alison M. Dunning, Douglas F. Easton, Paul D. P. Pharoah, Mikael Hartman, Jingmei Li

General Medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, oncology

11 May 2022

Ho, P. J., Khng, A. J., Tan, B. K.-T., Tan, E. Y., Tan, S.-M., Tan, V. K. M., Lim, G. H., Aronson, K. J., Chan, T. L., Choi, J.-Y., Dennis, J., Ho, W.-K., Hou, M.-F., Ito, H., Iwasaki, M., John, E. M., Kang, D., Kim, S.-W., Kurian, A. W., … Li, J. (2022). Relevance of the MHC region for breast cancer susceptibility in Asians. Breast Cancer, 29(5), 869–879. https://doi.org/10.1007/s12282-022-01366-w

Abstract Background Human leukocyte antigen (HLA) genes play critical roles in immune surveillance, an important defence against tumors. Imputing HLA genotypes from existing single-nucleotide polymorphism datasets is low-cost and efficient. We investigate the relevance of the major histocompatibility complex region in breast cancer susceptibility, using imputed class I and II HLA alleles, in 25,484 women of Asian ancestry. Methods A total of 12,901 breast cancer cases and 12,583 controls from 12 case–control studies were included in our pooled analysis. HLA imputation was performed using SNP2HLA on 10,886 quality-controlled variants within the 15–55 Mb region on chromosome 6. HLA alleles (n = 175) with info scores greater than 0.8 and frequencies greater than 0.01 were included (resolution at two-digit level: 71; four-digit level: 104). We studied the associations between HLA alleles and breast cancer risk using logistic regression, adjusting for population structure and age. Associations between HLA alleles and the risk of subtypes of breast cancer (ER-positive, ER-negative, HER2-positive, HER2-negative, early-stage, and late-stage) were examined. Results We did not observe associations between any HLA allele and breast cancer risk at P < 5e−8; the smallest p value was observed for HLA-C*12:03 (OR = 1.29, P = 1.08e−3). Ninety-five percent of the effect sizes (OR) observed were between 0.90 and 1.23. Similar results were observed when different subtypes of breast cancer were studied (95% of ORs were between 0.85 and 1.18). Conclusions No imputed HLA allele was associated with breast cancer risk in our large Asian study. Direct measurement of HLA gene expressions may be required to further explore the associations between HLA genes and breast cancer risk.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the National Research Foundation - NRF Fellowship
Grant Reference no. : NRF-NRFF2017-02

This research / project is supported by the National University of Singapore - NUS start-up Grant
Grant Reference no. : NA

This research / project is supported by the National University Cancer Institute Singapore - Centre Grant
Grant Reference no. : NA

This research / project is supported by the Saw Swee Hock School of Public Health - Research Seed Funding - Breast Cancer Prevention Programme
Grant Reference no. : SSHSPH-Res-Prog-BCPP

This research / project is supported by the Yong Loo Lin School of Medicine - Asian Breast Cancer Research Fund
Grant Reference no. : NA

This research / project is supported by the National Medical Research Council - Clinician Scientist Award - Senior Investigator Category
Grant Reference no. : NMRC/CSA-SI/0015/2017

Population-based controls were from the Multi-Ethnic Cohort (MEC) funded by grants from the Ministry of Health, Singapore, National University of Singapore and National University Health System, Singapore.

https://oar.a-star.edu.sg/communities-collections/articles/19025

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