Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population

Krista A. Zanetti; Zhaoming Wang; Melinda Aldrich; Christopher I. Amos; William J. Blot; Elise D. Bowman; Laurie Burdette; Qiuyin Cai; Neil Caporaso; Charles C. Chung; Elizabeth M. Gillanders; Christopher A. Haiman; Helen M. Hansen; Brian E. Henderson; Laurence N. Kolonel; Loic Le Marchand; Shengchao Li; Lorna Haughton McNeill; Bríd M. Ryan; Ann G. Schwartz; Jennette D. Sison; Margaret R. Spitz; Margaret Tucker; Angela S. Wenzlaff; John K. Wiencke; Lynne Wilkens; Margaret R. Wrensch; Xifeng Wu; Wei Zheng; Weiyin Zhou; David Christiani; Julie R. Palmer; Trevor M. Penning; Alyssa G. Rieber; Lynn Rosenberg; Edward A. Ruiz-Narvaez; Li Su; Anil Vachani; Yongyue Wei; Alexander S. Whitehead; Stephen J. Chanock; Curtis C. Harris

doi:10.1016/j.lungcan.2016.05.008

Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population

Krista A. Zanetti, Zhaoming Wang, Melinda Aldrich, Christopher I. Amos, William J. Blot, Elise D. Bowman, Laurie Burdette, Qiuyin Cai, Neil Caporaso, Charles C. Chung, Elizabeth M. Gillanders, Christopher A. Haiman, Helen M. Hansen, Brian E. Henderson, Laurence N. Kolonel, Loic Le Marchand, Shengchao Li, Lorna Haughton McNeill, Bríd M. Ryan, Ann G. SchwartzJennette D. Sison, Margaret R. Spitz, Margaret Tucker, Angela S. Wenzlaff, John K. Wiencke, Lynne Wilkens, Margaret R. Wrensch, Xifeng Wu, Wei Zheng, Weiyin Zhou, David Christiani, Julie R. Palmer, Trevor M. Penning, Alyssa G. Rieber, Lynn Rosenberg, Edward A. Ruiz-Narvaez, Li Su, Anil Vachani, Yongyue Wei, Alexander S. Whitehead, Stephen J. Chanock, Curtis C. Harris

School of Medicine

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

27 Scopus citations

Abstract

Objectives: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. Materials and methods: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p < 1.51 × 10^-5) in an independent set of 866 cases and 796 controls in stage 2. Results and conclusion: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p = 1.3 × 10^-9; OR = 1.32; 95% CI = 1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p = 2.8 × 10^-9; OR = 1.28; 95% CI = 1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p = 1.3 × 10^-8; OR = 1.37; 95% CI = 1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.

Original language	English (US)
Pages (from-to)	33-42
Number of pages	10
Journal	Lung Cancer
Volume	98
DOIs	https://doi.org/10.1016/j.lungcan.2016.05.008
State	Published - Aug 1 2016

Keywords

African Americans
Genome-wide association study
Lung neoplasms
Receptors, Cholinergic
Smoking
Telomerase

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

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10.1016/j.lungcan.2016.05.008

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Zanetti, K. A., Wang, Z., Aldrich, M., Amos, C. I., Blot, W. J., Bowman, E. D., Burdette, L., Cai, Q., Caporaso, N., Chung, C. C., Gillanders, E. M., Haiman, C. A., Hansen, H. M., Henderson, B. E., Kolonel, L. N., Marchand, L. L., Li, S., McNeill, L. H., Ryan, B. M., ... Harris, C. C. (2016). Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population. Lung Cancer, 98, 33-42. https://doi.org/10.1016/j.lungcan.2016.05.008

Zanetti, KA, Wang, Z, Aldrich, M, Amos, CI, Blot, WJ, Bowman, ED, Burdette, L, Cai, Q, Caporaso, N, Chung, CC, Gillanders, EM, Haiman, CA, Hansen, HM, Henderson, BE, Kolonel, LN, Marchand, LL, Li, S, McNeill, LH, Ryan, BM, Schwartz, AG, Sison, JD, Spitz, MR, Tucker, M, Wenzlaff, AS, Wiencke, JK, Wilkens, L, Wrensch, MR, Wu, X, Zheng, W, Zhou, W, Christiani, D, Palmer, JR, Penning, TM, Rieber, AG, Rosenberg, L, Ruiz-Narvaez, EA, Su, L, Vachani, A, Wei, Y, Whitehead, AS, Chanock, SJ & Harris, CC 2016, 'Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population', Lung Cancer, vol. 98, pp. 33-42. https://doi.org/10.1016/j.lungcan.2016.05.008

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title = "Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population",

abstract = "Objectives: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. Materials and methods: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p < 1.51 × 10-5) in an independent set of 866 cases and 796 controls in stage 2. Results and conclusion: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p = 1.3 × 10-9; OR = 1.32; 95% CI = 1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p = 2.8 × 10-9; OR = 1.28; 95% CI = 1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p = 1.3 × 10-8; OR = 1.37; 95% CI = 1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.",

keywords = "African Americans, Genome-wide association study, Lung neoplasms, Receptors, Cholinergic, Smoking, Telomerase",

author = "Zanetti, {Krista A.} and Zhaoming Wang and Melinda Aldrich and Amos, {Christopher I.} and Blot, {William J.} and Bowman, {Elise D.} and Laurie Burdette and Qiuyin Cai and Neil Caporaso and Chung, {Charles C.} and Gillanders, {Elizabeth M.} and Haiman, {Christopher A.} and Hansen, {Helen M.} and Henderson, {Brian E.} and Kolonel, {Laurence N.} and Marchand, {Loic Le} and Shengchao Li and McNeill, {Lorna Haughton} and Ryan, {Br{\'i}d M.} and Schwartz, {Ann G.} and Sison, {Jennette D.} and Spitz, {Margaret R.} and Margaret Tucker and Wenzlaff, {Angela S.} and Wiencke, {John K.} and Lynne Wilkens and Wrensch, {Margaret R.} and Xifeng Wu and Wei Zheng and Weiyin Zhou and David Christiani and Palmer, {Julie R.} and Penning, {Trevor M.} and Rieber, {Alyssa G.} and Lynn Rosenberg and Ruiz-Narvaez, {Edward A.} and Li Su and Anil Vachani and Yongyue Wei and Whitehead, {Alexander S.} and Chanock, {Stephen J.} and Harris, {Curtis C.}",

note = "Publisher Copyright: {\textcopyright} 2016.",

year = "2016",

month = aug,

day = "1",

doi = "10.1016/j.lungcan.2016.05.008",

language = "English (US)",

volume = "98",

pages = "33--42",

journal = "Lung Cancer",

issn = "0169-5002",

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TY - JOUR

T1 - Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population

AU - Zanetti, Krista A.

AU - Wang, Zhaoming

AU - Aldrich, Melinda

AU - Amos, Christopher I.

AU - Blot, William J.

AU - Bowman, Elise D.

AU - Burdette, Laurie

AU - Cai, Qiuyin

AU - Caporaso, Neil

AU - Chung, Charles C.

AU - Gillanders, Elizabeth M.

AU - Haiman, Christopher A.

AU - Hansen, Helen M.

AU - Henderson, Brian E.

AU - Kolonel, Laurence N.

AU - Marchand, Loic Le

AU - Li, Shengchao

AU - McNeill, Lorna Haughton

AU - Ryan, Bríd M.

AU - Schwartz, Ann G.

AU - Sison, Jennette D.

AU - Spitz, Margaret R.

AU - Tucker, Margaret

AU - Wenzlaff, Angela S.

AU - Wiencke, John K.

AU - Wilkens, Lynne

AU - Wrensch, Margaret R.

AU - Wu, Xifeng

AU - Zheng, Wei

AU - Zhou, Weiyin

AU - Christiani, David

AU - Palmer, Julie R.

AU - Penning, Trevor M.

AU - Rieber, Alyssa G.

AU - Rosenberg, Lynn

AU - Ruiz-Narvaez, Edward A.

AU - Su, Li

AU - Vachani, Anil

AU - Wei, Yongyue

AU - Whitehead, Alexander S.

AU - Chanock, Stephen J.

AU - Harris, Curtis C.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Objectives: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. Materials and methods: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p < 1.51 × 10-5) in an independent set of 866 cases and 796 controls in stage 2. Results and conclusion: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p = 1.3 × 10-9; OR = 1.32; 95% CI = 1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p = 2.8 × 10-9; OR = 1.28; 95% CI = 1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p = 1.3 × 10-8; OR = 1.37; 95% CI = 1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.

AB - Objectives: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. Materials and methods: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p < 1.51 × 10-5) in an independent set of 866 cases and 796 controls in stage 2. Results and conclusion: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p = 1.3 × 10-9; OR = 1.32; 95% CI = 1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p = 2.8 × 10-9; OR = 1.28; 95% CI = 1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p = 1.3 × 10-8; OR = 1.37; 95% CI = 1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.

KW - African Americans

KW - Genome-wide association study

KW - Lung neoplasms

KW - Receptors, Cholinergic

KW - Smoking

KW - Telomerase

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ER -

Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population

Abstract

Keywords

ASJC Scopus subject areas

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