HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Yoon Ming Chin; Taisei Mushiroda; Atsushi Takahashi; Michiaki Kubo; Gopala Krishnan; Lee Fah Yap; Soo Hwang Teo; Paul Vey Hong Lim; Yoke Yeow Yap; Kin Choo Pua; Naoyuki Kamatani; Yusuke Nakamura; Choon Kook Sam; Alan Soo Beng Khoo; S. Subathra; N. Punithavati; B. S. Tan; Y. S. Ee; L. M. Ong; R. A. Hamid; M. Goh; J. C.T. Quah; J. Lim; B. D. Dipak; R. Deepak; F. N. Lau; P. V. Kam; S. Shri Devi; C. A. Ong; C. L. Lum; N. A. Ahmad; S. Halimuddin; M. Somasundran; A. Kam; M. Wodjin; S. K. Subramaniam; T. S. Tiong; T. Y. Tan; U. H. Sim; T. W. Tharumalingam; D. Norlida; M. Zulkarnaen; W. H. Lai; A. Z. Bustam; S. Marniza; P. Shahfinaz; O. Hashim; S. Shamshinder; N. Prepageran; L. M. Looi; O. Rahmat; J. Amin; J. Maznan; S. Hassan; B. Biswal; A. Munirah; A. Subasri; L. P. Tan; N. M. Kumaran; M. S. Nurul Ashikin; M. S. Nursyazwani; B. Norhasimah; R. Sasela Devi; C. Y. Koh; Ching Ching Ng

doi:10.1002/ijc.29035

HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Yoon Ming Chin, Taisei Mushiroda, Atsushi Takahashi, Michiaki Kubo, Gopala Krishnan, Lee Fah Yap, Soo Hwang Teo, Paul Vey Hong Lim, Yoke Yeow Yap, Kin Choo Pua, Naoyuki Kamatani, Yusuke Nakamura, Choon Kook Sam, Alan Soo Beng Khoo, S. Subathra, N. Punithavati, B. S. Tan, Y. S. Ee, L. M. Ong, R. A. HamidM. Goh, J. C.T. Quah, J. Lim, B. D. Dipak, R. Deepak, F. N. Lau, P. V. Kam, S. Shri Devi, C. A. Ong, C. L. Lum, N. A. Ahmad, S. Halimuddin, M. Somasundran, A. Kam, M. Wodjin, S. K. Subramaniam, T. S. Tiong, T. Y. Tan, U. H. Sim, T. W. Tharumalingam, D. Norlida, M. Zulkarnaen, W. H. Lai, A. Z. Bustam, S. Marniza, P. Shahfinaz, O. Hashim, S. Shamshinder, N. Prepageran, L. M. Looi, O. Rahmat, J. Amin, J. Maznan, S. Hassan, B. Biswal, A. Munirah, A. Subasri, L. P. Tan, N. M. Kumaran, M. S. Nurul Ashikin, M. S. Nursyazwani, B. Norhasimah, R. Sasela Devi, C. Y. Koh, Ching Ching Ng

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Abstract

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p=1.73 3 10^-9). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p_{HLA-A-aa-site-99}=3.79 × 10^-8, p_rs1136697=3.79 × 10^-8) and T-cell receptor binding site (p_{HLA-A-aa-site-145}=1.41 × 1024, p_rs1059520=1.41 × 10^-4) of the HLA-A. We also detected strong association signals in the 50-UTR region with predicted active promoter states (p_rs41545520=7.91 × 10^-8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A∗11:01, and to a lesser extent HLA-A∗02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese.

Original language	English
Pages (from-to)	678-687
Number of pages	10
Journal	International Journal of Cancer
Volume	136
Issue number	3
DOIs	https://doi.org/10.1002/ijc.29035
Publication status	Published - 15-02-2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ijc.29035

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Chin, Y. M., Mushiroda, T., Takahashi, A., Kubo, M., Krishnan, G., Yap, L. F., Teo, S. H., Lim, P. V. H., Yap, Y. Y., Pua, K. C., Kamatani, N., Nakamura, Y., Sam, C. K., Khoo, A. S. B., Subathra, S., Punithavati, N., Tan, B. S., Ee, Y. S., Ong, L. M., ... Ng, C. C. (2015). HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese. International Journal of Cancer, 136(3), 678-687. https://doi.org/10.1002/ijc.29035

@article{d1e1eefa83514d11af73eb9d7f5a3611,

title = "HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese",

abstract = "Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p=1.73 3 10-9). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (pHLA-A-aa-site-99=3.79 × 10-8, prs1136697=3.79 × 10-8) and T-cell receptor binding site (pHLA-A-aa-site-145=1.41 × 1024, prs1059520=1.41 × 10-4) of the HLA-A. We also detected strong association signals in the 50-UTR region with predicted active promoter states (prs41545520=7.91 × 10-8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A∗11:01, and to a lesser extent HLA-A∗02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese.",

author = "Chin, {Yoon Ming} and Taisei Mushiroda and Atsushi Takahashi and Michiaki Kubo and Gopala Krishnan and Yap, {Lee Fah} and Teo, {Soo Hwang} and Lim, {Paul Vey Hong} and Yap, {Yoke Yeow} and Pua, {Kin Choo} and Naoyuki Kamatani and Yusuke Nakamura and Sam, {Choon Kook} and Khoo, {Alan Soo Beng} and S. Subathra and N. Punithavati and Tan, {B. S.} and Ee, {Y. S.} and Ong, {L. M.} and Hamid, {R. A.} and M. Goh and Quah, {J. C.T.} and J. Lim and Dipak, {B. D.} and R. Deepak and Lau, {F. N.} and Kam, {P. V.} and {Shri Devi}, S. and Ong, {C. A.} and Lum, {C. L.} and Ahmad, {N. A.} and S. Halimuddin and M. Somasundran and A. Kam and M. Wodjin and Subramaniam, {S. K.} and Tiong, {T. S.} and Tan, {T. Y.} and Sim, {U. H.} and Tharumalingam, {T. W.} and D. Norlida and M. Zulkarnaen and Lai, {W. H.} and Bustam, {A. Z.} and S. Marniza and P. Shahfinaz and O. Hashim and S. Shamshinder and N. Prepageran and Looi, {L. M.} and O. Rahmat and J. Amin and J. Maznan and S. Hassan and B. Biswal and A. Munirah and A. Subasri and Tan, {L. P.} and Kumaran, {N. M.} and {Nurul Ashikin}, {M. S.} and Nursyazwani, {M. S.} and B. Norhasimah and {Sasela Devi}, R. and Koh, {C. Y.} and Ng, {Ching Ching}",

note = "Publisher Copyright: {\textcopyright} 2014 UICC.",

year = "2015",

month = feb,

day = "15",

doi = "10.1002/ijc.29035",

language = "English",

volume = "136",

pages = "678--687",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "Wiley-Liss Inc.",

number = "3",

}

Chin, YM, Mushiroda, T, Takahashi, A, Kubo, M, Krishnan, G, Yap, LF, Teo, SH, Lim, PVH, Yap, YY, Pua, KC, Kamatani, N, Nakamura, Y, Sam, CK, Khoo, ASB, Subathra, S, Punithavati, N, Tan, BS, Ee, YS, Ong, LM, Hamid, RA, Goh, M, Quah, JCT, Lim, J, Dipak, BD, Deepak, R, Lau, FN, Kam, PV, Shri Devi, S, Ong, CA, Lum, CL, Ahmad, NA, Halimuddin, S, Somasundran, M, Kam, A, Wodjin, M, Subramaniam, SK, Tiong, TS, Tan, TY, Sim, UH, Tharumalingam, TW, Norlida, D, Zulkarnaen, M, Lai, WH, Bustam, AZ, Marniza, S, Shahfinaz, P, Hashim, O, Shamshinder, S, Prepageran, N, Looi, LM, Rahmat, O, Amin, J, Maznan, J, Hassan, S, Biswal, B, Munirah, A, Subasri, A, Tan, LP, Kumaran, NM, Nurul Ashikin, MS, Nursyazwani, MS, Norhasimah, B, Sasela Devi, R, Koh, CY & Ng, CC 2015, 'HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese', International Journal of Cancer, vol. 136, no. 3, pp. 678-687. https://doi.org/10.1002/ijc.29035

TY - JOUR

T1 - HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

AU - Chin, Yoon Ming

AU - Mushiroda, Taisei

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Krishnan, Gopala

AU - Yap, Lee Fah

AU - Teo, Soo Hwang

AU - Lim, Paul Vey Hong

AU - Yap, Yoke Yeow

AU - Pua, Kin Choo

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Sam, Choon Kook

AU - Khoo, Alan Soo Beng

AU - Subathra, S.

AU - Punithavati, N.

AU - Tan, B. S.

AU - Ee, Y. S.

AU - Ong, L. M.

AU - Hamid, R. A.

AU - Goh, M.

AU - Quah, J. C.T.

AU - Lim, J.

AU - Dipak, B. D.

AU - Deepak, R.

AU - Lau, F. N.

AU - Kam, P. V.

AU - Shri Devi, S.

AU - Ong, C. A.

AU - Lum, C. L.

AU - Ahmad, N. A.

AU - Halimuddin, S.

AU - Somasundran, M.

AU - Kam, A.

AU - Wodjin, M.

AU - Subramaniam, S. K.

AU - Tiong, T. S.

AU - Tan, T. Y.

AU - Sim, U. H.

AU - Tharumalingam, T. W.

AU - Norlida, D.

AU - Zulkarnaen, M.

AU - Lai, W. H.

AU - Bustam, A. Z.

AU - Marniza, S.

AU - Shahfinaz, P.

AU - Hashim, O.

AU - Shamshinder, S.

AU - Prepageran, N.

AU - Looi, L. M.

AU - Rahmat, O.

AU - Amin, J.

AU - Maznan, J.

AU - Hassan, S.

AU - Biswal, B.

AU - Munirah, A.

AU - Subasri, A.

AU - Tan, L. P.

AU - Kumaran, N. M.

AU - Nurul Ashikin, M. S.

AU - Nursyazwani, M. S.

AU - Norhasimah, B.

AU - Sasela Devi, R.

AU - Koh, C. Y.

AU - Ng, Ching Ching

PY - 2015/2/15

Y1 - 2015/2/15

N2 - Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p=1.73 3 10-9). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (pHLA-A-aa-site-99=3.79 × 10-8, prs1136697=3.79 × 10-8) and T-cell receptor binding site (pHLA-A-aa-site-145=1.41 × 1024, prs1059520=1.41 × 10-4) of the HLA-A. We also detected strong association signals in the 50-UTR region with predicted active promoter states (prs41545520=7.91 × 10-8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A∗11:01, and to a lesser extent HLA-A∗02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese.

AB - Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p=1.73 3 10-9). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (pHLA-A-aa-site-99=3.79 × 10-8, prs1136697=3.79 × 10-8) and T-cell receptor binding site (pHLA-A-aa-site-145=1.41 × 1024, prs1059520=1.41 × 10-4) of the HLA-A. We also detected strong association signals in the 50-UTR region with predicted active promoter states (prs41545520=7.91 × 10-8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A∗11:01, and to a lesser extent HLA-A∗02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese.

UR - http://www.scopus.com/inward/record.url?scp=84911005348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911005348&partnerID=8YFLogxK

U2 - 10.1002/ijc.29035

DO - 10.1002/ijc.29035

M3 - Article

C2 - 24947555

AN - SCOPUS:84911005348

SN - 0020-7136

VL - 136

SP - 678

EP - 687

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 3

ER -

HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

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