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Relevance of the MHC region for breast cancer susceptibility in Asians

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 comple...

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Autores principales: Ho, Peh Joo, Khng, Alexis Jiaying, Tan, Benita Kiat-Tee, Tan, Ern Yu, Tan, Su-Ming, Tan, Veronique Kiak Mien, Lim, Geok Hoon, Aronson, Kristan J., Chan, Tsun L., Choi, Ji-Yeob, Dennis, Joe, Ho, Weang-Kee, Hou, Ming-Feng, Ito, Hidemi, Iwasaki, Motoki, John, Esther M., Kang, Daehee, Kim, Sung-Won, Kurian, Allison W., Kwong, Ava, Lophatananon, Artitaya, Matsuo, Keitaro, Mohd-Taib, Nur Aishah, Muir, Kenneth, Murphy, Rachel A., Park, Sue K., Shen, Chen-Yang, Shu, Xiao-Ou, Teo, Soo Hwang, Wang, Qin, Yamaji, Taiki, Zheng, Wei, Bolla, Manjeet K., Dunning, Alison M., Easton, Douglas F., Pharoah, Paul D. P., Hartman, Mikael, Li, Jingmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385763/
https://www.ncbi.nlm.nih.gov/pubmed/35543923
http://dx.doi.org/10.1007/s12282-022-01366-w
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author Ho, Peh Joo
Khng, Alexis Jiaying
Tan, Benita Kiat-Tee
Tan, Ern Yu
Tan, Su-Ming
Tan, Veronique Kiak Mien
Lim, Geok Hoon
Aronson, Kristan J.
Chan, Tsun L.
Choi, Ji-Yeob
Dennis, Joe
Ho, Weang-Kee
Hou, Ming-Feng
Ito, Hidemi
Iwasaki, Motoki
John, Esther M.
Kang, Daehee
Kim, Sung-Won
Kurian, Allison W.
Kwong, Ava
Lophatananon, Artitaya
Matsuo, Keitaro
Mohd-Taib, Nur Aishah
Muir, Kenneth
Murphy, Rachel A.
Park, Sue K.
Shen, Chen-Yang
Shu, Xiao-Ou
Teo, Soo Hwang
Wang, Qin
Yamaji, Taiki
Zheng, Wei
Bolla, Manjeet K.
Dunning, Alison M.
Easton, Douglas F.
Pharoah, Paul D. P.
Hartman, Mikael
Li, Jingmei
author_facet Ho, Peh Joo
Khng, Alexis Jiaying
Tan, Benita Kiat-Tee
Tan, Ern Yu
Tan, Su-Ming
Tan, Veronique Kiak Mien
Lim, Geok Hoon
Aronson, Kristan J.
Chan, Tsun L.
Choi, Ji-Yeob
Dennis, Joe
Ho, Weang-Kee
Hou, Ming-Feng
Ito, Hidemi
Iwasaki, Motoki
John, Esther M.
Kang, Daehee
Kim, Sung-Won
Kurian, Allison W.
Kwong, Ava
Lophatananon, Artitaya
Matsuo, Keitaro
Mohd-Taib, Nur Aishah
Muir, Kenneth
Murphy, Rachel A.
Park, Sue K.
Shen, Chen-Yang
Shu, Xiao-Ou
Teo, Soo Hwang
Wang, Qin
Yamaji, Taiki
Zheng, Wei
Bolla, Manjeet K.
Dunning, Alison M.
Easton, Douglas F.
Pharoah, Paul D. P.
Hartman, Mikael
Li, Jingmei
author_sort Ho, Peh Joo
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12282-022-01366-w.
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spelling pubmed-93857632022-08-19 Relevance of the MHC region for breast cancer susceptibility in Asians Ho, Peh Joo Khng, Alexis Jiaying Tan, Benita Kiat-Tee Tan, Ern Yu Tan, Su-Ming Tan, Veronique Kiak Mien Lim, Geok Hoon Aronson, Kristan J. Chan, Tsun L. Choi, Ji-Yeob Dennis, Joe Ho, Weang-Kee Hou, Ming-Feng Ito, Hidemi Iwasaki, Motoki John, Esther M. Kang, Daehee Kim, Sung-Won Kurian, Allison W. Kwong, Ava Lophatananon, Artitaya Matsuo, Keitaro Mohd-Taib, Nur Aishah Muir, Kenneth Murphy, Rachel A. Park, Sue K. Shen, Chen-Yang Shu, Xiao-Ou Teo, Soo Hwang Wang, Qin Yamaji, Taiki Zheng, Wei Bolla, Manjeet K. Dunning, Alison M. Easton, Douglas F. Pharoah, Paul D. P. Hartman, Mikael Li, Jingmei Breast Cancer Original Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12282-022-01366-w. Springer Nature Singapore 2022-05-11 2022 /pmc/articles/PMC9385763/ /pubmed/35543923 http://dx.doi.org/10.1007/s12282-022-01366-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Ho, Peh Joo
Khng, Alexis Jiaying
Tan, Benita Kiat-Tee
Tan, Ern Yu
Tan, Su-Ming
Tan, Veronique Kiak Mien
Lim, Geok Hoon
Aronson, Kristan J.
Chan, Tsun L.
Choi, Ji-Yeob
Dennis, Joe
Ho, Weang-Kee
Hou, Ming-Feng
Ito, Hidemi
Iwasaki, Motoki
John, Esther M.
Kang, Daehee
Kim, Sung-Won
Kurian, Allison W.
Kwong, Ava
Lophatananon, Artitaya
Matsuo, Keitaro
Mohd-Taib, Nur Aishah
Muir, Kenneth
Murphy, Rachel A.
Park, Sue K.
Shen, Chen-Yang
Shu, Xiao-Ou
Teo, Soo Hwang
Wang, Qin
Yamaji, Taiki
Zheng, Wei
Bolla, Manjeet K.
Dunning, Alison M.
Easton, Douglas F.
Pharoah, Paul D. P.
Hartman, Mikael
Li, Jingmei
Relevance of the MHC region for breast cancer susceptibility in Asians
title Relevance of the MHC region for breast cancer susceptibility in Asians
title_full Relevance of the MHC region for breast cancer susceptibility in Asians
title_fullStr Relevance of the MHC region for breast cancer susceptibility in Asians
title_full_unstemmed Relevance of the MHC region for breast cancer susceptibility in Asians
title_short Relevance of the MHC region for breast cancer susceptibility in Asians
title_sort relevance of the mhc region for breast cancer susceptibility in asians
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385763/
https://www.ncbi.nlm.nih.gov/pubmed/35543923
http://dx.doi.org/10.1007/s12282-022-01366-w
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