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dc.contributor.authorHo, Peh Joo
dc.contributor.authorKhng, Alexis Jiaying
dc.contributor.authorTan, Benita Kiat-Tee
dc.contributor.authorTan, Ern Yu
dc.contributor.authorTan, Su-Ming
dc.contributor.authorTan, Veronique Kiak Mien
dc.contributor.authorLim, Geok Hoon
dc.contributor.authorAronson, Kristan J
dc.contributor.authorChan, Tsun L
dc.contributor.authorChoi, Ji-Yeob
dc.contributor.authorDennis, Joe
dc.contributor.authorHo, Weang-Kee
dc.contributor.authorHou, Ming-Feng
dc.contributor.authorIto, Hidemi
dc.contributor.authorIwasaki, Motoki
dc.contributor.authorJohn, Esther M
dc.contributor.authorKang, Daehee
dc.contributor.authorKim, Sung-Won
dc.contributor.authorKurian, Allison W
dc.contributor.authorKwong, Ava
dc.contributor.authorLophatananon, Artitaya
dc.contributor.authorMatsuo, Keitaro
dc.contributor.authorMohd-Taib, Nur Aishah
dc.contributor.authorMuir, Kenneth
dc.contributor.authorMurphy, Rachel A
dc.contributor.authorPark, Sue K
dc.contributor.authorShen, Chen-Yang
dc.contributor.authorShu, Xiao-Ou
dc.contributor.authorTeo, Soo Hwang
dc.contributor.authorWang, Qin
dc.contributor.authorYamaji, Taiki
dc.contributor.authorZheng, Wei
dc.contributor.authorBolla, Manjeet K
dc.contributor.authorDunning, Alison M
dc.contributor.authorEaston, Douglas
dc.contributor.authorPharoah, Paul
dc.contributor.authorHartman, Mikael
dc.contributor.authorLi, Jingmei
dc.description.abstractBACKGROUND: 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.
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.subjectBreast cancer risk
dc.subjectBreast cancer subtypes
dc.titleRelevance of the MHC region for breast cancer susceptibility in Asians.
dc.publisher.departmentDepartment of Public Health And Primary Care, Cancer Genetic Epidemiology
prism.publicationNameBreast Cancer
dc.contributor.orcidDennis, Joe [0000-0003-4591-1214]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidLi, Jingmei [0000-0001-8587-7511]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Cancer Institute (U19CA148537)
pubs.funder-project-idEuropean Commission (223175)
pubs.funder-project-idNational Cancer Institute (R01CA128978)
pubs.funder-project-idNational Cancer Institute (U19CA148065)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634935)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (633784)
pubs.funder-project-idCancer Research UK (A10710)
pubs.funder-project-idCancer Research UK (A16563)
pubs.funder-project-idCancer Research UK (A12014)
pubs.funder-project-idCancer Research UK (A10118)
pubs.funder-project-idWellcome Trust (203477/Z/16/Z)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
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