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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Abstract 62: A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population.

Kouya Shiraishi, Hideo Kunitoh, Yataro Daigo, Atsushi Takahashi, Koichi Goto, Hiromi Sakamoto, Sumiko Ohnami, Yoko Shimada, Kyota Ashikawa, Akira Saito, Shun-ichi Watanabe, Koji Tsuta, Naoyuki Kamatani, Teruhiko Yoshida, Yusuke Nakamura, Jun Yokota, Michiaki Kubo and Takashi Kohno
Kouya Shiraishi
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Hideo Kunitoh
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Yataro Daigo
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Atsushi Takahashi
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Koichi Goto
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Hiromi Sakamoto
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Sumiko Ohnami
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Yoko Shimada
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Kyota Ashikawa
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Akira Saito
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Shun-ichi Watanabe
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Koji Tsuta
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Naoyuki Kamatani
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Teruhiko Yoshida
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Yusuke Nakamura
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Jun Yokota
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Michiaki Kubo
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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Takashi Kohno
1National Cancer Center Research Institute, Tokyo, Japan, 2National Cancer Center Hospital, Tokyo, Japan, 3Shiga University of Medical Science, Shiga, Japan, 4RIKEN, Kanagawa, Japan, 5National Cancer Center Hospital East, Chiba, Japan, 6StaGen Co, Tokyo, Japan, 7University of Tokyo, Tokyo, Japan.
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DOI: 10.1158/1055-9965.GWAS-62 Published November 2012
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Abstract

Adenocarcinoma is the most common type, comprising ˜40% of all lung cancer cases, and its incidence is increasing both in Asian and Western countries. The development of lung adenocarcinoma is more weakly associated with smoking than other histological types of lung cancer, such as squamous and small cell carcinomas, indicating that the mechanisms of carcinogenesis differ among these types. A better understanding of the genetic factors underlying lung adenocarcinoma development is strongly needed to elucidate the disease etiology and to identify high-risk individuals for targeted screening and/or prevention. To identify genetic factors that influence the risk of lung adenocarcinoma, we conducted a genome-wide association study and two validation studies in the Japanese population that consisted of a total of 6,029 lung adenocarcinoma cases and 13,535 controls (Shiraishi et al, Nat Genet, 2012).

Associations of two previously reported loci, 5p15.33 (rs2853677 in TERT; PCombined = 2.8x10-40, odds ratio (OR) = 1.41) and 3q28 (rs10937405 in TP63; PCombined = 6.9x10-17, OR = 1.25) (Landi et al, AJHG, 2009; Miki et al, Nat Genet, 2010), were validated. In addition, we identified two new susceptibility loci, 17q24.3 (rs7216064 in BPTF; PCombined = 7.4x10-11, OR = 1.20) and 6p21.3 (rs3817963 in BTNL2; PCombined = 2.7x10-10, OR = 1.18). BPTF encodes a chromatin remodeling factor that regulates transcription via specific recognition of methylated histone proteins. BPTF mRNA levels in noncancerous lung tissues were different depending on the genotype of the rs7216064 SNP (P = 0.02), implying a low expression from the risk allele. The BTNL2 gene encodes a T cell co-stimulatory molecule, and associations between BTNL2 SNPs and risk have been reported in several immune-related diseases. These data provide further evidence supporting genetic susceptibility to the development of lung adenocarcinoma.

Citation Format: Kouya Shiraishi, Hideo Kunitoh, Yataro Daigo, Atsushi Takahashi, Koichi Goto, Hiromi Sakamoto, Sumiko Ohnami, Yoko Shimada, Kyota Ashikawa, Akira Saito, Shunichi Watanabe, Koji Tsuta, Naoyuki Kamatani, Teruhiko Yoshida, Yusuke Nakamura, Jun Yokota, Michiaki Kubo, Takashi Kohno. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 62.

  • ©2012 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 21 (11 Supplement)
November 2012
Volume 21, Issue 11 Supplement
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Abstract 62: A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population.
Kouya Shiraishi, Hideo Kunitoh, Yataro Daigo, Atsushi Takahashi, Koichi Goto, Hiromi Sakamoto, Sumiko Ohnami, Yoko Shimada, Kyota Ashikawa, Akira Saito, Shun-ichi Watanabe, Koji Tsuta, Naoyuki Kamatani, Teruhiko Yoshida, Yusuke Nakamura, Jun Yokota, Michiaki Kubo and Takashi Kohno
Cancer Epidemiol Biomarkers Prev November 1 2012 (21) (11 Supplement) 62; DOI: 10.1158/1055-9965.GWAS-62

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Abstract 62: A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population.
Kouya Shiraishi, Hideo Kunitoh, Yataro Daigo, Atsushi Takahashi, Koichi Goto, Hiromi Sakamoto, Sumiko Ohnami, Yoko Shimada, Kyota Ashikawa, Akira Saito, Shun-ichi Watanabe, Koji Tsuta, Naoyuki Kamatani, Teruhiko Yoshida, Yusuke Nakamura, Jun Yokota, Michiaki Kubo and Takashi Kohno
Cancer Epidemiol Biomarkers Prev November 1 2012 (21) (11 Supplement) 62; DOI: 10.1158/1055-9965.GWAS-62
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