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 complex...
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my.um.eprints.417262025-01-17T07:03:18Z http://eprints.um.edu.my/41726/ 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 RC0254 Neoplasms. Tumors. Oncology (including Cancer) RG Gynecology and obstetrics 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. Springer 2022-09 Article PeerReviewed Ho, Peh Joo and Khng, Alexis Jiaying and Tan, Benita Kiat-Tee and Tan, Ern Yu and Tan, Su-Ming and Tan, Veronique Kiak Mien and Lim, Geok Hoon and Aronson, Kristan J. and Chan, Tsun L. and Choi, Ji-Yeob and Dennis, Joe and Ho, Weang-Kee and Hou, Ming-Feng and Ito, Hidemi and Iwasaki, Motoki and John, Esther M. and Kang, Daehee and Kim, Sung-Won and Kurian, Allison W. and Kwong, Ava and Lophatananon, Artitaya and Matsuo, Keitaro and Mohd-Taib, Nur Aishah and Muir, Kenneth and Murphy, Rachel A. and Park, Sue K. and Shen, Chen-Yang and Shu, Xiao-Ou and Teo, Soo Hwang and Wang, Qin and Yamaji, Taiki and Zheng, Wei and Bolla, Manjeet K. and Dunning, Alison M. and Easton, Douglas F. and Pharoah, Paul D. P. and Hartman, Mikael and Li, Jingmei (2022) Relevance of the MHC region for breast cancer susceptibility in Asians. Breast Cancer, 29 (5). pp. 869-879. ISSN 1340-6868, DOI https://doi.org/10.1007/s12282-022-01366-w <https://doi.org/10.1007/s12282-022-01366-w>. https://doi.org/10.1007/s12282-022-01366-w 10.1007/s12282-022-01366-w |
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RC0254 Neoplasms. Tumors. Oncology (including Cancer) RG Gynecology and obstetrics |
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RC0254 Neoplasms. Tumors. Oncology (including Cancer) RG Gynecology and obstetrics 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 |
| 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. |
| format |
Article |
| 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 |
| title |
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_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_sort |
relevance of the mhc region for breast cancer susceptibility in asians |
| publisher |
Springer |
| publishDate |
2022 |
| url |
http://eprints.um.edu.my/41726/ https://doi.org/10.1007/s12282-022-01366-w |
| _version_ |
1825160584020099072 |
| score |
13.239859 |