Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Kouya Shiraishi; Yukinori Okada; Atsushi Takahashi; Yoichiro Kamatani; Yukihide Momozawa; Kyota Ashikawa; Hideo Kunitoh; Shingo Matsumoto; Atsushi Takano; Kimihiro Shimizu; Akiteru Goto; Koji Tsuta; Shun Ichi Watanabe; Yuichiro Ohe; Yukio Watanabe; Yasushi Goto; Hiroshi Nokihara; Koh Furuta; Akihiko Yoshida; Koichi Goto; Tomoyuki Hishida; Masahiro Tsuboi; Katsuya Tsuchihara; Yohei Miyagi; Haruhiko Nakayama; Tomoyuki Yokose; Kazumi Tanaka; Toshiteru Nagashima; Yoichi Ohtaki; Daichi Maeda; Kazuhiro Imai; Yoshihiro Minamiya; Hiromi Sakamoto; Akira Saito; Yoko Shimada; Kuniko Sunami; Motonobu Saito; Johji Inazawa; Yusuke Nakamura; Teruhiko Yoshida; Jun Yokota; Fumihiko Matsuda; Keitaro Matsuo; Yataro Daigo; Michiaki Kubo; Takashi Kohno

doi:10.1038/ncomms12451

Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Kouya Shiraishi, Yukinori Okada, Atsushi Takahashi, Yoichiro Kamatani, Yukihide Momozawa, Kyota Ashikawa, Hideo Kunitoh, Shingo Matsumoto, Atsushi Takano, Kimihiro Shimizu, Akiteru Goto, Koji Tsuta, Shun Ichi Watanabe, Yuichiro Ohe, Yukio Watanabe, Yasushi Goto, Hiroshi Nokihara, Koh Furuta, Akihiko Yoshida, Koichi GotoTomoyuki Hishida, Masahiro Tsuboi, Katsuya Tsuchihara, Yohei Miyagi, Haruhiko Nakayama, Tomoyuki Yokose, Kazumi Tanaka, Toshiteru Nagashima, Yoichi Ohtaki, Daichi Maeda, Kazuhiro Imai, Yoshihiro Minamiya, Hiromi Sakamoto, Akira Saito, Yoko Shimada, Kuniko Sunami, Motonobu Saito, Johji Inazawa, Yusuke Nakamura, Teruhiko Yoshida, Jun Yokota, Fumihiko Matsuda, Keitaro Matsuo, Yataro Daigo, Michiaki Kubo, Takashi Kohno

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Abstract

Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10 '17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10 '9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.

Original language	English
Article number	12451
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12451
Publication status	Published - 09-08-2016
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms12451

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Shiraishi, K., Okada, Y., Takahashi, A., Kamatani, Y., Momozawa, Y., Ashikawa, K., Kunitoh, H., Matsumoto, S., Takano, A., Shimizu, K., Goto, A., Tsuta, K., Watanabe, S. I., Ohe, Y., Watanabe, Y., Goto, Y., Nokihara, H., Furuta, K., Yoshida, A., ... Kohno, T. (2016). Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. Nature communications, 7, Article 12451. https://doi.org/10.1038/ncomms12451

@article{67fde661aa894cac92fd006cfec2b42a,

title = "Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma",

abstract = "Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10 '17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10 '9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.",

author = "Kouya Shiraishi and Yukinori Okada and Atsushi Takahashi and Yoichiro Kamatani and Yukihide Momozawa and Kyota Ashikawa and Hideo Kunitoh and Shingo Matsumoto and Atsushi Takano and Kimihiro Shimizu and Akiteru Goto and Koji Tsuta and Watanabe, {Shun Ichi} and Yuichiro Ohe and Yukio Watanabe and Yasushi Goto and Hiroshi Nokihara and Koh Furuta and Akihiko Yoshida and Koichi Goto and Tomoyuki Hishida and Masahiro Tsuboi and Katsuya Tsuchihara and Yohei Miyagi and Haruhiko Nakayama and Tomoyuki Yokose and Kazumi Tanaka and Toshiteru Nagashima and Yoichi Ohtaki and Daichi Maeda and Kazuhiro Imai and Yoshihiro Minamiya and Hiromi Sakamoto and Akira Saito and Yoko Shimada and Kuniko Sunami and Motonobu Saito and Johji Inazawa and Yusuke Nakamura and Teruhiko Yoshida and Jun Yokota and Fumihiko Matsuda and Keitaro Matsuo and Yataro Daigo and Michiaki Kubo and Takashi Kohno",

note = "Funding Information: This research was supported in part by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED: 16ck0106096h0003); the Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers 15H05911, 15H05670, 15K14429, 22590516, 19390359; the Princess Takamatsu Cancer Research Fund; and by the National Cancer Center Research and Development Fund (26-A-8 and 26-A-1:",

year = "2016",

month = aug,

day = "9",

doi = "10.1038/ncomms12451",

language = "English",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Shiraishi, K, Okada, Y, Takahashi, A, Kamatani, Y, Momozawa, Y, Ashikawa, K, Kunitoh, H, Matsumoto, S, Takano, A, Shimizu, K, Goto, A, Tsuta, K, Watanabe, SI, Ohe, Y, Watanabe, Y, Goto, Y, Nokihara, H, Furuta, K, Yoshida, A, Goto, K, Hishida, T, Tsuboi, M, Tsuchihara, K, Miyagi, Y, Nakayama, H, Yokose, T, Tanaka, K, Nagashima, T, Ohtaki, Y, Maeda, D, Imai, K, Minamiya, Y, Sakamoto, H, Saito, A, Shimada, Y, Sunami, K, Saito, M, Inazawa, J, Nakamura, Y, Yoshida, T, Yokota, J, Matsuda, F, Matsuo, K, Daigo, Y, Kubo, M & Kohno, T 2016, 'Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma', Nature communications, vol. 7, 12451. https://doi.org/10.1038/ncomms12451

TY - JOUR

T1 - Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

AU - Shiraishi, Kouya

AU - Okada, Yukinori

AU - Takahashi, Atsushi

AU - Kamatani, Yoichiro

AU - Momozawa, Yukihide

AU - Ashikawa, Kyota

AU - Kunitoh, Hideo

AU - Matsumoto, Shingo

AU - Takano, Atsushi

AU - Shimizu, Kimihiro

AU - Goto, Akiteru

AU - Tsuta, Koji

AU - Watanabe, Shun Ichi

AU - Ohe, Yuichiro

AU - Watanabe, Yukio

AU - Goto, Yasushi

AU - Nokihara, Hiroshi

AU - Furuta, Koh

AU - Yoshida, Akihiko

AU - Goto, Koichi

AU - Hishida, Tomoyuki

AU - Tsuboi, Masahiro

AU - Tsuchihara, Katsuya

AU - Miyagi, Yohei

AU - Nakayama, Haruhiko

AU - Yokose, Tomoyuki

AU - Tanaka, Kazumi

AU - Nagashima, Toshiteru

AU - Ohtaki, Yoichi

AU - Maeda, Daichi

AU - Imai, Kazuhiro

AU - Minamiya, Yoshihiro

AU - Sakamoto, Hiromi

AU - Saito, Akira

AU - Shimada, Yoko

AU - Sunami, Kuniko

AU - Saito, Motonobu

AU - Inazawa, Johji

AU - Nakamura, Yusuke

AU - Yoshida, Teruhiko

AU - Yokota, Jun

AU - Matsuda, Fumihiko

AU - Matsuo, Keitaro

AU - Daigo, Yataro

AU - Kubo, Michiaki

AU - Kohno, Takashi

N1 - Funding Information: This research was supported in part by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED: 16ck0106096h0003); the Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers 15H05911, 15H05670, 15K14429, 22590516, 19390359; the Princess Takamatsu Cancer Research Fund; and by the National Cancer Center Research and Development Fund (26-A-8 and 26-A-1:

PY - 2016/8/9

Y1 - 2016/8/9

N2 - Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10 '17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10 '9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.

AB - Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10 '17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10 '9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.

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U2 - 10.1038/ncomms12451

DO - 10.1038/ncomms12451

M3 - Article

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AN - SCOPUS:84982146157

SN - 2041-1723

VL - 7

JO - Nature communications

JF - Nature communications

M1 - 12451

ER -

Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

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