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Relevance of the MHC region for breast cancer susceptibility in Asians

Ho PJ 1 , Khng AJ 1 , Tan BK 2 , Tan EY 3 , Tan SM 4 , Tan VKM 2 Show all authors , Lim GH 5 , Aronson KJ 6 , Chan TL 7 , Choi JY 8 , Dennis J 9 , Ho WK 10 , Hou MF 11 , Ito H 12 , Iwasaki M 13 , John EM 14 , Kang D 15 , Kim SW 16 , Kurian AW 14 , Kwong A 7 , Lophatananon A 17 , Matsuo K 18 , Mohd-Taib NA 19 , Muir K 17 , Murphy RA 20 , Park SK 15 , Shen CY 21 , Shu XO 22 , Teo SH 23 , Wang Q 9 , Yamaji T 13 , Zheng W 22 , Bolla MK 9 , Dunning AM 9 , Easton DF 9 , Pharoah PDP 9 , Hartman M 24 , Li J 25

Affiliations 

  • 1 Women's Health and Genetics, Genome Institute of Singapore, 60 Biopolis Street, Genome, #02-01, Singapore, 138672, Singapore
  • 2 Department of Breast Surgery, Singapore General Hospital, Singapore, Singapore
  • 3 Department of General Surgery, Tan Tock Seng Hospital, Singapore, 308433, Singapore
  • 4 Division of Breast Surgery, Changi General Hospital, Singapore, Singapore
  • 5 KK Breast Department, KK Women's and Children's Hospital, Singapore, 229899, Singapore
  • 6 Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, ON, K7L 3N6, Canada
  • 7 Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong, Hong Kong
  • 8 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 03080, Korea
  • 9 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK
  • 10 Department of Mathematical Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia Campus, 43500, Semenyih, Selangor, Malaysia
  • 11 Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kao-hsiung, 812, Taiwan
  • 12 Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan
  • 13 Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, 104-0045, Japan
  • 14 Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, 94305, USA
  • 15 Cancer Research Institute, Seoul National University, Seoul, 03080, Korea
  • 16 Department of Surgery, Daerim Saint Mary's Hospital, Seoul, 07442, Korea
  • 17 Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PL, UK
  • 18 Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
  • 19 Department of Surgery, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
  • 20 School of Population and Public Health, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada
  • 21 Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan
  • 22 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
  • 23 Breast Cancer Research Programme, Cancer Research Malaysia, 47500, Subang Jaya, Selangor, Malaysia
  • 24 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 119077, Singapore
  • 25 Women's Health and Genetics, Genome Institute of Singapore, 60 Biopolis Street, Genome, #02-01, Singapore, 138672, Singapore. lijm1@gis.a-star.edu.sg
Breast Cancer, 2022 Sep;29(5):869-879.
PMID: 35543923 DOI: 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 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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