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 & 26 others 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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 languageEnglish
Article number12451
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 09-08-2016

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loci
lungs
mutations
magnetic permeability
Mutation
Genes
Alleles
genome
Validation Studies
Genome-Wide Association Study
Adenocarcinoma of lung
conduction

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Shiraishi, K., Okada, Y., Takahashi, A., Kamatani, Y., Momozawa, Y., Ashikawa, K., ... Kohno, T. (2016). Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. Nature Communications, 7, [12451]. https://doi.org/10.1038/ncomms12451
Shiraishi, Kouya ; Okada, Yukinori ; Takahashi, Atsushi ; Kamatani, Yoichiro ; Momozawa, Yukihide ; Ashikawa, Kyota ; Kunitoh, Hideo ; Matsumoto, Shingo ; Takano, Atsushi ; Shimizu, Kimihiro ; Goto, Akiteru ; Tsuta, Koji ; Watanabe, Shun Ichi ; Ohe, Yuichiro ; Watanabe, Yukio ; Goto, Yasushi ; Nokihara, Hiroshi ; Furuta, Koh ; Yoshida, Akihiko ; Goto, Koichi ; Hishida, Tomoyuki ; Tsuboi, Masahiro ; Tsuchihara, Katsuya ; Miyagi, Yohei ; Nakayama, Haruhiko ; Yokose, Tomoyuki ; Tanaka, Kazumi ; Nagashima, Toshiteru ; Ohtaki, Yoichi ; Maeda, Daichi ; Imai, Kazuhiro ; Minamiya, Yoshihiro ; Sakamoto, Hiromi ; Saito, Akira ; Shimada, Yoko ; Sunami, Kuniko ; Saito, Motonobu ; Inazawa, Johji ; Nakamura, Yusuke ; Yoshida, Teruhiko ; Yokota, Jun ; Matsuda, Fumihiko ; Matsuo, Keitaro ; Daigo, Yataro ; Kubo, Michiaki ; Kohno, Takashi. / Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. In: Nature Communications. 2016 ; Vol. 7.
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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.",
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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, 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

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

In: Nature Communications, Vol. 7, 12451, 09.08.2016.

Research output: Contribution to journalArticle

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

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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