Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia

Qing Lan; Chao A. Hsiung; Keitaro Matsuo; Yun Chul Hong; Adeline Seow; Zhaoming Wang; H. Dean Hosgood; Kexin Chen; Jiu Cun Wang; Nilanjan Chatterjee; Wei Hu; Maria Pik Wong; Wei Zheng; Neil Caporaso; Jae Yong Park; Chien Jen Chen; Yeul Hong Kim; Young Tae Kim; Maria Teresa Landi; Hongbing Shen; Charles Lawrence; Laurie Burdett; Meredith Yeager; Jeffrey Yuenger; Kevin B. Jacobs; I. Shou Chang; Tetsuya Mitsudomi; Hee Nam Kim; Gee Chen Chang; Bryan A. Bassig; Margaret Tucker; Fusheng Wei; Zhihua Yin; Chen Wu; She Juan An; Biyun Qian; Victor Ho Fun Lee; Daru Lu; Jianjun Liu; Hyo Sung Jeon; Chin Fu Hsiao; Jae Sook Sung; Jin Hee Kim; Yu Tang Gao; Ying Huang Tsai; Yoo Jin Jung; Huan Guo; Zhibin Hu; Amy Hutchinson; Wen Chang Wang; Robert Klein; Charles C. Chung; In Jae Oh; Kuan Yu Chen; Sonja I. Berndt; Xingzhou He; Wei Wu; Jiang Chang; Xu Chao Zhang; Ming Shyan Huang; Hong Zheng; Junwen Wang; Xueying Zhao; Yuqing Li; Jin Eun Choi; Wu Chou Su; Kyong Hwa Park; Sook Whan Sung; Xiao Ou Shu; Yuh Min Chen; Li Liu; Chang Hyun Kang; Lingmin Hu; Chung Hsing Chen; William Pao; Young Chul Kim; Tsung Ying Yang; Jun Xu; Peng Guan; Wen Tan; Jian Su; Chih Liang Wang; Haixin Li; Alan Dart Loon Sihoe; Zhenhong Zhao; Ying Chen; Yi Young Choi; Jen Yu Hung; Jun Suk Kim; Ho Il Yoon; Qiuyin Cai; Chien Chung Lin; In Kyu Park; Ping Xu; Jing Dong; Christopher Kim; Qincheng He; Reury Perng Perng; Takashi Kohno; Sun Seog Kweon; Chih Yi Chen; Roel Vermeulen; Junjie Wu; Wei Yen Lim; Kun Chieh Chen; Wong Ho Chow; Bu Tian Ji; John K.C. Chan; Minjie Chu; Yao Jen Li; Jun Yokota; Jihua Li; Hongyan Chen; Yong Bing Xiang; Chong Jen Yu; Hideo Kunitoh; Guoping Wu; Li Jin; Yen Li Lo; Kouya Shiraishi; Ying Hsiang Chen; Hsien Chih Lin; Tangchun Wu; Yi Long Wu; Pan Chyr Yang; Baosen Zhou; Min Ho Shin; Joseph F. Fraumeni; Dongxin Lin; Stephen J. Chanock; Nathaniel Rothman

doi:10.1038/ng.2456

Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia

Qing Lan^*
, Chao A. Hsiung
, Keitaro Matsuo
, Yun Chul Hong
, Adeline Seow
, Zhaoming Wang
, H. Dean Hosgood
, Kexin Chen
, Jiu Cun Wang
, Nilanjan Chatterjee
, Wei Hu
, Maria Pik Wong
, Wei Zheng
, Neil Caporaso
, Jae Yong Park
, Chien Jen Chen
, Yeul Hong Kim
, Young Tae Kim
, Maria Teresa Landi
, Hongbing Shen

Charles Lawrence, Laurie Burdett, Meredith Yeager, Jeffrey Yuenger, Kevin B. Jacobs, I. Shou Chang, Tetsuya Mitsudomi, Hee Nam Kim, Gee Chen Chang, Bryan A. Bassig, Margaret Tucker, Fusheng Wei, Zhihua Yin, Chen Wu, She Juan An, Biyun Qian, Victor Ho Fun Lee, Daru Lu, Jianjun Liu, Hyo Sung Jeon, Chin Fu Hsiao, Jae Sook Sung, Jin Hee Kim, Yu Tang Gao, Ying Huang Tsai, Yoo Jin Jung, Huan Guo, Zhibin Hu, Amy Hutchinson, Wen Chang Wang, Robert Klein, Charles C. Chung, In Jae Oh, Kuan Yu Chen, Sonja I. Berndt, Xingzhou He, Wei Wu, Jiang Chang, Xu Chao Zhang, Ming Shyan Huang, Hong Zheng, Junwen Wang, Xueying Zhao, Yuqing Li, Jin Eun Choi, Wu Chou Su, Kyong Hwa Park, Sook Whan Sung, Xiao Ou Shu, Yuh Min Chen, Li Liu, Chang Hyun Kang, Lingmin Hu, Chung Hsing Chen, William Pao, Young Chul Kim, Tsung Ying Yang, Jun Xu, Peng Guan, Wen Tan, Jian Su, Chih Liang Wang, Haixin Li, Alan Dart Loon Sihoe, Zhenhong Zhao, Ying Chen, Yi Young Choi, Jen Yu Hung, Jun Suk Kim, Ho Il Yoon, Qiuyin Cai, Chien Chung Lin, In Kyu Park, Ping Xu, Jing Dong, Christopher Kim, Qincheng He, Reury Perng Perng, Takashi Kohno, Sun Seog Kweon, Chih Yi Chen, Roel Vermeulen, Junjie Wu, Wei Yen Lim, Kun Chieh Chen, Wong Ho Chow, Bu Tian Ji, John K.C. Chan, Minjie Chu, Yao Jen Li, Jun Yokota, Jihua Li, Hongyan Chen, Yong Bing Xiang, Chong Jen Yu, Hideo Kunitoh, Guoping Wu, Li Jin, Yen Li Lo, Kouya Shiraishi, Ying Hsiang Chen, Hsien Chih Lin, Tangchun Wu, Yi Long Wu, Pan Chyr Yang, Baosen Zhou, Min Ho Shin, Joseph F. Fraumeni, Dongxin Lin, Stephen J. Chanock, Nathaniel Rothman

^*Corresponding author for this work

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

286 Citations (Scopus)

Abstract

To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

Original language	English
Pages (from-to)	1330-1335
Number of pages	6
Journal	Nature Genetics
Volume	44
Issue number	12
DOIs	https://doi.org/10.1038/ng.2456
Publication status	Published - 2012 Dec

Bibliographical note

Funding Information:
We thank J.-J. Yang, X.-N. Yang, Q. Zhou, W.-B. Guo, S.-L. Chen, Y. Huang, Z. Xie, J.-G. Chen, H.-H. Yan, K. Tajima, Y. Yatabe, T. Hida, K.-L. Chuah, A. Ng, P. Eng, S.-S. Leong, M.-K. Ang, E. Lim, T.-K. Lim, M. Teh, W.-T. Poh and A. Tee. The overall GWAS project was supported by the intramural program of the US National Institutes of Health/National Cancer Institute. A list of support provided to individual studies is provided in the Supplementary Note.

UN SDGs

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

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Genetics

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10.1038/ng.2456

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Lan, Q., Hsiung, C. A., Matsuo, K., Hong, Y. C., Seow, A., Wang, Z., Hosgood, H. D., Chen, K., Wang, J. C., Chatterjee, N., Hu, W., Wong, M. P., Zheng, W., Caporaso, N., Park, J. Y., Chen, C. J., Kim, Y. H., Kim, Y. T., Landi, M. T., ... Rothman, N. (2012). Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nature Genetics, 44(12), 1330-1335. https://doi.org/10.1038/ng.2456

Lan, Q, Hsiung, CA, Matsuo, K, Hong, YC, Seow, A, Wang, Z, Hosgood, HD, Chen, K, Wang, JC, Chatterjee, N, Hu, W, Wong, MP, Zheng, W, Caporaso, N, Park, JY, Chen, CJ, Kim, YH, Kim, YT, Landi, MT, Shen, H, Lawrence, C, Burdett, L, Yeager, M, Yuenger, J, Jacobs, KB, Chang, IS, Mitsudomi, T, Kim, HN, Chang, GC, Bassig, BA, Tucker, M, Wei, F, Yin, Z, Wu, C, An, SJ, Qian, B, Lee, VHF, Lu, D, Liu, J, Jeon, HS, Hsiao, CF, Sung, JS, Kim, JH, Gao, YT, Tsai, YH, Jung, YJ, Guo, H, Hu, Z, Hutchinson, A, Wang, WC, Klein, R, Chung, CC, Oh, IJ, Chen, KY, Berndt, SI, He, X, Wu, W, Chang, J, Zhang, XC, Huang, MS, Zheng, H, Wang, J, Zhao, X, Li, Y, Choi, JE, Su, WC, Park, KH, Sung, SW, Shu, XO, Chen, YM, Liu, L, Kang, CH, Hu, L, Chen, CH, Pao, W, Kim, YC, Yang, TY, Xu, J, Guan, P, Tan, W, Su, J, Wang, CL, Li, H, Sihoe, ADL, Zhao, Z, Chen, Y, Choi, YY, Hung, JY, Kim, JS, Yoon, HI, Cai, Q, Lin, CC, Park, IK, Xu, P, Dong, J, Kim, C, He, Q, Perng, RP, Kohno, T, Kweon, SS, Chen, CY, Vermeulen, R, Wu, J, Lim, WY, Chen, KC, Chow, WH, Ji, BT, Chan, JKC, Chu, M, Li, YJ, Yokota, J, Li, J, Chen, H, Xiang, YB, Yu, CJ, Kunitoh, H, Wu, G, Jin, L, Lo, YL, Shiraishi, K, Chen, YH, Lin, HC, Wu, T, Wu, YL, Yang, PC, Zhou, B, Shin, MH, Fraumeni, JF, Lin, D, Chanock, SJ & Rothman, N 2012, 'Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia', Nature Genetics, vol. 44, no. 12, pp. 1330-1335. https://doi.org/10.1038/ng.2456

@article{b987a7eca9e34e03a367ecba6a2f5986,

title = "Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia",

abstract = "To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.",

author = "Qing Lan and Hsiung, \{Chao A.\} and Keitaro Matsuo and Hong, \{Yun Chul\} and Adeline Seow and Zhaoming Wang and Hosgood, \{H. Dean\} and Kexin Chen and Wang, \{Jiu Cun\} and Nilanjan Chatterjee and Wei Hu and Wong, \{Maria Pik\} and Wei Zheng and Neil Caporaso and Park, \{Jae Yong\} and Chen, \{Chien Jen\} and Kim, \{Yeul Hong\} and Kim, \{Young Tae\} and Landi, \{Maria Teresa\} and Hongbing Shen and Charles Lawrence and Laurie Burdett and Meredith Yeager and Jeffrey Yuenger and Jacobs, \{Kevin B.\} and Chang, \{I. Shou\} and Tetsuya Mitsudomi and Kim, \{Hee Nam\} and Chang, \{Gee Chen\} and Bassig, \{Bryan A.\} and Margaret Tucker and Fusheng Wei and Zhihua Yin and Chen Wu and An, \{She Juan\} and Biyun Qian and Lee, \{Victor Ho Fun\} and Daru Lu and Jianjun Liu and Jeon, \{Hyo Sung\} and Hsiao, \{Chin Fu\} and Sung, \{Jae Sook\} and Kim, \{Jin Hee\} and Gao, \{Yu Tang\} and Tsai, \{Ying Huang\} and Jung, \{Yoo Jin\} and Huan Guo and Zhibin Hu and Amy Hutchinson and Wang, \{Wen Chang\} and Robert Klein and Chung, \{Charles C.\} and Oh, \{In Jae\} and Chen, \{Kuan Yu\} and Berndt, \{Sonja I.\} and Xingzhou He and Wei Wu and Jiang Chang and Zhang, \{Xu Chao\} and Huang, \{Ming Shyan\} and Hong Zheng and Junwen Wang and Xueying Zhao and Yuqing Li and Choi, \{Jin Eun\} and Su, \{Wu Chou\} and Park, \{Kyong Hwa\} and Sung, \{Sook Whan\} and Shu, \{Xiao Ou\} and Chen, \{Yuh Min\} and Li Liu and Kang, \{Chang Hyun\} and Lingmin Hu and Chen, \{Chung Hsing\} and William Pao and Kim, \{Young Chul\} and Yang, \{Tsung Ying\} and Jun Xu and Peng Guan and Wen Tan and Jian Su and Wang, \{Chih Liang\} and Haixin Li and Sihoe, \{Alan Dart Loon\} and Zhenhong Zhao and Ying Chen and Choi, \{Yi Young\} and Hung, \{Jen Yu\} and Kim, \{Jun Suk\} and Yoon, \{Ho Il\} and Qiuyin Cai and Lin, \{Chien Chung\} and Park, \{In Kyu\} and Ping Xu and Jing Dong and Christopher Kim and Qincheng He and Perng, \{Reury Perng\} and Takashi Kohno and Kweon, \{Sun Seog\} and Chen, \{Chih Yi\} and Roel Vermeulen and Junjie Wu and Lim, \{Wei Yen\} and Chen, \{Kun Chieh\} and Chow, \{Wong Ho\} and Ji, \{Bu Tian\} and Chan, \{John K.C.\} and Minjie Chu and Li, \{Yao Jen\} and Jun Yokota and Jihua Li and Hongyan Chen and Xiang, \{Yong Bing\} and Yu, \{Chong Jen\} and Hideo Kunitoh and Guoping Wu and Li Jin and Lo, \{Yen Li\} and Kouya Shiraishi and Chen, \{Ying Hsiang\} and Lin, \{Hsien Chih\} and Tangchun Wu and Wu, \{Yi Long\} and Yang, \{Pan Chyr\} and Baosen Zhou and Shin, \{Min Ho\} and Fraumeni, \{Joseph F.\} and Dongxin Lin and Chanock, \{Stephen J.\} and Nathaniel Rothman",

note = "Funding Information: We thank J.-J. Yang, X.-N. Yang, Q. Zhou, W.-B. Guo, S.-L. Chen, Y. Huang, Z. Xie, J.-G. Chen, H.-H. Yan, K. Tajima, Y. Yatabe, T. Hida, K.-L. Chuah, A. Ng, P. Eng, S.-S. Leong, M.-K. Ang, E. Lim, T.-K. Lim, M. Teh, W.-T. Poh and A. Tee. The overall GWAS project was supported by the intramural program of the US National Institutes of Health/National Cancer Institute. A list of support provided to individual studies is provided in the Supplementary Note.",

year = "2012",

month = dec,

doi = "10.1038/ng.2456",

language = "English",

volume = "44",

pages = "1330--1335",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

}

TY - JOUR

T1 - Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia

AU - Lan, Qing

AU - Hsiung, Chao A.

AU - Matsuo, Keitaro

AU - Hong, Yun Chul

AU - Seow, Adeline

AU - Wang, Zhaoming

AU - Hosgood, H. Dean

AU - Chen, Kexin

AU - Wang, Jiu Cun

AU - Chatterjee, Nilanjan

AU - Hu, Wei

AU - Wong, Maria Pik

AU - Zheng, Wei

AU - Caporaso, Neil

AU - Park, Jae Yong

AU - Chen, Chien Jen

AU - Kim, Yeul Hong

AU - Kim, Young Tae

AU - Landi, Maria Teresa

AU - Shen, Hongbing

AU - Lawrence, Charles

AU - Burdett, Laurie

AU - Yeager, Meredith

AU - Yuenger, Jeffrey

AU - Jacobs, Kevin B.

AU - Chang, I. Shou

AU - Mitsudomi, Tetsuya

AU - Kim, Hee Nam

AU - Chang, Gee Chen

AU - Bassig, Bryan A.

AU - Tucker, Margaret

AU - Wei, Fusheng

AU - Yin, Zhihua

AU - Wu, Chen

AU - An, She Juan

AU - Qian, Biyun

AU - Lee, Victor Ho Fun

AU - Lu, Daru

AU - Liu, Jianjun

AU - Jeon, Hyo Sung

AU - Hsiao, Chin Fu

AU - Sung, Jae Sook

AU - Kim, Jin Hee

AU - Gao, Yu Tang

AU - Tsai, Ying Huang

AU - Jung, Yoo Jin

AU - Guo, Huan

AU - Hu, Zhibin

AU - Hutchinson, Amy

AU - Wang, Wen Chang

AU - Klein, Robert

AU - Chung, Charles C.

AU - Oh, In Jae

AU - Chen, Kuan Yu

AU - Berndt, Sonja I.

AU - He, Xingzhou

AU - Wu, Wei

AU - Chang, Jiang

AU - Zhang, Xu Chao

AU - Huang, Ming Shyan

AU - Zheng, Hong

AU - Wang, Junwen

AU - Zhao, Xueying

AU - Li, Yuqing

AU - Choi, Jin Eun

AU - Su, Wu Chou

AU - Park, Kyong Hwa

AU - Sung, Sook Whan

AU - Shu, Xiao Ou

AU - Chen, Yuh Min

AU - Liu, Li

AU - Kang, Chang Hyun

AU - Hu, Lingmin

AU - Chen, Chung Hsing

AU - Pao, William

AU - Kim, Young Chul

AU - Yang, Tsung Ying

AU - Xu, Jun

AU - Guan, Peng

AU - Tan, Wen

AU - Su, Jian

AU - Wang, Chih Liang

AU - Li, Haixin

AU - Sihoe, Alan Dart Loon

AU - Zhao, Zhenhong

AU - Chen, Ying

AU - Choi, Yi Young

AU - Hung, Jen Yu

AU - Kim, Jun Suk

AU - Yoon, Ho Il

AU - Cai, Qiuyin

AU - Lin, Chien Chung

AU - Park, In Kyu

AU - Xu, Ping

AU - Dong, Jing

AU - Kim, Christopher

AU - He, Qincheng

AU - Perng, Reury Perng

AU - Kohno, Takashi

AU - Kweon, Sun Seog

AU - Chen, Chih Yi

AU - Vermeulen, Roel

AU - Wu, Junjie

AU - Lim, Wei Yen

AU - Chen, Kun Chieh

AU - Chow, Wong Ho

AU - Ji, Bu Tian

AU - Chan, John K.C.

AU - Chu, Minjie

AU - Li, Yao Jen

AU - Yokota, Jun

AU - Li, Jihua

AU - Chen, Hongyan

AU - Xiang, Yong Bing

AU - Yu, Chong Jen

AU - Kunitoh, Hideo

AU - Wu, Guoping

AU - Jin, Li

AU - Lo, Yen Li

AU - Shiraishi, Kouya

AU - Chen, Ying Hsiang

AU - Lin, Hsien Chih

AU - Wu, Tangchun

AU - Wu, Yi Long

AU - Yang, Pan Chyr

AU - Zhou, Baosen

AU - Shin, Min Ho

AU - Fraumeni, Joseph F.

AU - Lin, Dongxin

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

N1 - Funding Information: We thank J.-J. Yang, X.-N. Yang, Q. Zhou, W.-B. Guo, S.-L. Chen, Y. Huang, Z. Xie, J.-G. Chen, H.-H. Yan, K. Tajima, Y. Yatabe, T. Hida, K.-L. Chuah, A. Ng, P. Eng, S.-S. Leong, M.-K. Ang, E. Lim, T.-K. Lim, M. Teh, W.-T. Poh and A. Tee. The overall GWAS project was supported by the intramural program of the US National Institutes of Health/National Cancer Institute. A list of support provided to individual studies is provided in the Supplementary Note.

PY - 2012/12

Y1 - 2012/12

N2 - To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

AB - To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

UR - https://www.scopus.com/pages/publications/84870502715

U2 - 10.1038/ng.2456

DO - 10.1038/ng.2456

M3 - Article

C2 - 23143601

AN - SCOPUS:84870502715

SN - 1061-4036

VL - 44

SP - 1330

EP - 1335

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia

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Bibliographical note

UN SDGs

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