Relevance of the MHC region for breast cancer susceptibility in Asians

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 KwongArtitaya 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)869-879
Number of pages11
JournalBreast Cancer
Volume29
Issue number5
DOIs
StatePublished - Sep 2022

Keywords

  • Breast cancer risk
  • Breast cancer subtypes
  • HLA

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