Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

Jennifer Luyapan; Yohan Bosse; Zhonglin Li; Xiangjun Xiao; Albert Rosenberger; Rayjean J. Hung; Stephen Lam; Shanbeh Zienolddiny; Geoffrey Liu; Lambertus A. Kiemeney; Chu Chen; James McKay; Mattias Johansson; Mikael Johansson; Adonina Tardon; Guillermo Fernandez-Tardon; Paul Brennan; John K. Field; Michael P. Davies; Penella J. Woll; Angela Cox; Fiona Taylor; Susanne M. Arnold; Philip Lazarus; Kjell Grankvist; Maria T. Landi; David C. Christiani; Todd A. MacKenzie; Christopher I. Amos

doi:10.1093/hmg/ddad095

Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

Jennifer Luyapan
, Yohan Bosse
, Zhonglin Li
, Xiangjun Xiao
, Albert Rosenberger
, Rayjean J. Hung
, Stephen Lam
, Shanbeh Zienolddiny
, Geoffrey Liu
, Lambertus A. Kiemeney
, Chu Chen
, James McKay
, Mattias Johansson
, Mikael Johansson
, Adonina Tardon
, Guillermo Fernandez-Tardon
, Paul Brennan
, John K. Field
, Michael P. Davies
, Penella J. Woll

Angela Cox, Fiona Taylor, Susanne M. Arnold, Philip Lazarus, Kjell Grankvist, Maria T. Landi, David C. Christiani, Todd A. MacKenzie, Christopher I. Amos

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

11 Scopus citations

Abstract

Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.89-0.93, P = 7.64 × 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95% CI = 1.10-1.21, P = 1.27 × 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data - CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.80-0.96, P = 5.76 × 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95% CI = 1.01-1.28, P = 3.25 × 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95% CI = 0.85-0.92, P = 1.94 × 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95% CI = 1.14-1.27, P = 4.25 × 10-11) associated with overall lung cancer in the discovery data and validated in the replication data - CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.79-0.97, P = 1.64 × 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95% CI = 1.01-1.30, P = 3.81 × 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 × 10-4) and SFTA2 (PTWAS = 2.32 × 10-6).

Original language	English
Pages (from-to)	2842-2855
Number of pages	14
Journal	Human Molecular Genetics
Volume	32
Issue number	18
DOIs	https://doi.org/10.1093/hmg/ddad095
State	Published - Sep 15 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press. All rights reserved.

Funding

National Institute of Health (NIH), National Library of Medicine (NLM) Institute research grant T32LM012204, NIH research grant 5U01CA209414, National Cancer Institute (NCI) grant U19CA203654 and the Cancer Prevention Research Institute of Texas (CPRIT) RR170048. NCI U19CA203654 and CPRIT RR170048 funded the design, data collection, analysis and interpretation of the study. NIH-NLM T32LM012204 funded the analysis and interpretation of the data and in writing the manuscript. NIH 5U01CA209414 funded the data collection and interpretation of the data analyses.

Funders	Funder number
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	U19CA203654
National Childhood Cancer Registry – National Cancer Institute
U.S. National Library of Medicine	5U01CA209414, T32LM012204
U.S. National Library of Medicine
Cancer Prevention and Research Institute of Texas	RR170048
Cancer Prevention and Research Institute of Texas

UN SDGs

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

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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10.1093/hmg/ddad095

Cite this

Luyapan, J., Bosse, Y., Li, Z., Xiao, X., Rosenberger, A., Hung, R. J., Lam, S., Zienolddiny, S., Liu, G., Kiemeney, L. A., Chen, C., McKay, J., Johansson, M., Johansson, M., Tardon, A., Fernandez-Tardon, G., Brennan, P., Field, J. K., Davies, M. P., ... Amos, C. I. (2023). Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk. Human Molecular Genetics, 32(18), 2842-2855. https://doi.org/10.1093/hmg/ddad095

@article{c7b8dd5f5c644404aa9f4da22abcc934,

title = "Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk",

abstract = "Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95\% confidence interval (CI) = 0.89-0.93, P = 7.64 {\texttimes} 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95\% CI = 1.10-1.21, P = 1.27 {\texttimes} 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data - CTSH (rs34577742 C > T, OR = 0.88, 95\% CI = 0.80-0.96, P = 5.76 {\texttimes} 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95\% CI = 1.01-1.28, P = 3.25 {\texttimes} 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95\% CI = 0.85-0.92, P = 1.94 {\texttimes} 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95\% CI = 1.14-1.27, P = 4.25 {\texttimes} 10-11) associated with overall lung cancer in the discovery data and validated in the replication data - CTSH (rs34577742 C > T, OR = 0.88, 95\% CI = 0.79-0.97, P = 1.64 {\texttimes} 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95\% CI = 1.01-1.30, P = 3.81 {\texttimes} 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 {\texttimes} 10-4) and SFTA2 (PTWAS = 2.32 {\texttimes} 10-6).",

author = "Jennifer Luyapan and Yohan Bosse and Zhonglin Li and Xiangjun Xiao and Albert Rosenberger and Hung, \{Rayjean J.\} and Stephen Lam and Shanbeh Zienolddiny and Geoffrey Liu and Kiemeney, \{Lambertus A.\} and Chu Chen and James McKay and Mattias Johansson and Mikael Johansson and Adonina Tardon and Guillermo Fernandez-Tardon and Paul Brennan and Field, \{John K.\} and Davies, \{Michael P.\} and Woll, \{Penella J.\} and Angela Cox and Fiona Taylor and Arnold, \{Susanne M.\} and Philip Lazarus and Kjell Grankvist and Landi, \{Maria T.\} and Christiani, \{David C.\} and MacKenzie, \{Todd A.\} and Amos, \{Christopher I.\}",

year = "2023",

month = sep,

day = "15",

doi = "10.1093/hmg/ddad095",

language = "English",

volume = "32",

pages = "2842--2855",

number = "18",

}

Luyapan, J, Bosse, Y, Li, Z, Xiao, X, Rosenberger, A, Hung, RJ, Lam, S, Zienolddiny, S, Liu, G, Kiemeney, LA, Chen, C, McKay, J, Johansson, M, Johansson, M, Tardon, A, Fernandez-Tardon, G, Brennan, P, Field, JK, Davies, MP, Woll, PJ, Cox, A, Taylor, F, Arnold, SM, Lazarus, P, Grankvist, K, Landi, MT, Christiani, DC, MacKenzie, TA & Amos, CI 2023, 'Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk', Human Molecular Genetics, vol. 32, no. 18, pp. 2842-2855. https://doi.org/10.1093/hmg/ddad095

TY - JOUR

T1 - Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

AU - Luyapan, Jennifer

AU - Bosse, Yohan

AU - Li, Zhonglin

AU - Xiao, Xiangjun

AU - Rosenberger, Albert

AU - Hung, Rayjean J.

AU - Lam, Stephen

AU - Zienolddiny, Shanbeh

AU - Liu, Geoffrey

AU - Kiemeney, Lambertus A.

AU - Chen, Chu

AU - McKay, James

AU - Johansson, Mattias

AU - Johansson, Mikael

AU - Tardon, Adonina

AU - Fernandez-Tardon, Guillermo

AU - Brennan, Paul

AU - Field, John K.

AU - Davies, Michael P.

AU - Woll, Penella J.

AU - Cox, Angela

AU - Taylor, Fiona

AU - Arnold, Susanne M.

AU - Lazarus, Philip

AU - Grankvist, Kjell

AU - Landi, Maria T.

AU - Christiani, David C.

AU - MacKenzie, Todd A.

AU - Amos, Christopher I.

PY - 2023/9/15

Y1 - 2023/9/15

N2 - Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.89-0.93, P = 7.64 × 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95% CI = 1.10-1.21, P = 1.27 × 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data - CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.80-0.96, P = 5.76 × 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95% CI = 1.01-1.28, P = 3.25 × 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95% CI = 0.85-0.92, P = 1.94 × 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95% CI = 1.14-1.27, P = 4.25 × 10-11) associated with overall lung cancer in the discovery data and validated in the replication data - CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.79-0.97, P = 1.64 × 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95% CI = 1.01-1.30, P = 3.81 × 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 × 10-4) and SFTA2 (PTWAS = 2.32 × 10-6).

AB - Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.89-0.93, P = 7.64 × 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95% CI = 1.10-1.21, P = 1.27 × 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data - CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.80-0.96, P = 5.76 × 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95% CI = 1.01-1.28, P = 3.25 × 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95% CI = 0.85-0.92, P = 1.94 × 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95% CI = 1.14-1.27, P = 4.25 × 10-11) associated with overall lung cancer in the discovery data and validated in the replication data - CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.79-0.97, P = 1.64 × 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95% CI = 1.01-1.30, P = 3.81 × 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 × 10-4) and SFTA2 (PTWAS = 2.32 × 10-6).

UR - https://www.scopus.com/pages/publications/85169846740

UR - https://www.scopus.com/pages/publications/85169846740#tab=citedBy

U2 - 10.1093/hmg/ddad095

DO - 10.1093/hmg/ddad095

M3 - Article

C2 - 37471639

AN - SCOPUS:85169846740

SN - 0964-6906

VL - 32

SP - 2842

EP - 2855

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 18

ER -

Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

Access to Document

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