Citations 3
Genome-wide interaction analysis identified low-frequency variants with sex disparity in lung cancer risk
Li, Yafang , Xiao, Xiangjun , Cheng, Chao , McKay, James , Lam, Stephen , Tardón, Adonina , Chen, Chu, Bojesen, Stig E. , Landi, Maria Teresa , Risch, Angela , Wichmann, H‐Erich, Rennert, Gad , Goodman, Gary E. , Field, John K. , Davies, Michael P.A. , Shete, Sanjay , Melander, Olle , Brunnström, Hans , Hung, Rayjean J, Andrew, Angeline S. , Shen, Hongbing , Zienolddiny, Shan, Grankvist, Kjell , Johansson, Mikael , Caporaso, Neil E. , Aldrich, Melinda C. , Schwartz, Ann G. , Gorlov, Ivan P. , Purrington, Kristen S. , Bailey‐Wilson, Joan E. , Mandal, Diptasri , Willey, James C. , Gaba, Colette , Brennan, Paul , Hung, Rayjean J. , Rennert, Gad , Cheng, Chao , Wilson, Richard K , Hung, Rayjean J , Field, John K , Tardón, Adonina , Davies, Michael P A , Bojesen, Stig E , Risch, Angela , Grankvist, Kjell , Purrington, Kristen S , Willey, James C , Shen, Hongbing , Li, Jianrong , Byun, Jinyoung , Bossé, Yohan , Albanes, Demetrius , Johansson, Mattias , Bickeböller, Heike , Christiani, David C. , Arnold, Susanne M. , Marchand, Loı̈c Le , Liu, Geoffrey , Kiemeney, Lambertus A. , Sun, Ryan , Teare, M. Dawn , Hong, Yun‐Chul , Lazarus, Philip J. , Schabath, Matthew B. , Yang, Ping , Liu, Yanhong , Han, Younghun , Pinney, Susan M. , Amos, Christopher I.
Human Molecular Genetics | February 1, 2022 | Volume: 31 | Issue: 16 | Pages: 2831-2843
Abstract Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene–sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 [odds ratio (OR) = 0.71, P = 4.29×10−8); rs79942605 (OR = 2.17, P = 2.81×10−8) and rs208908 (OR = 0.70, P = 4.54×10−8) were identified with different risk effect of lung cancer between men and women. Further expression quantitative trait loci and functional annotation analysis suggested rs208908 affects lung cancer risk through differential regulation of Coxsackie virus and adenovirus receptor gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.
Genome-wide interaction analysis identified low-frequency variants with sex disparity in lung cancer risk
Li, Yafang , Xiao, Xiangjun , Byun, Jinyoung , Cheng, Chao , Bossé, Yohan , McKay, James , Lam, Stephen , Tardón, Adonina , Chen, Chu , Landi, Maria Teresa , Wichmann, Erich, Goodman, Gary, Field, John K. , Shete, Sanjay , Melander, Olle , Andrew, Angeline S. , Grankvist, Kjell , Johansson, Mikael , Caporaso, Neil E. , Aldrich, Melinda C. , Schwartz, Ann G. , Gorlov, Ivan P. , Purrington, Kristen S. , Yang, Ping , Bailey‐Wilson, Joan E. , Liu, Yanhong , Mandal, Diptasri , Gaba, Colette , Brennan, Paul , Cheng, Chao , Wilson, Richard K , Field, John K , Tardón, Adonina , Bossé, Yohan , Grankvist, Kjell , Purrington, Kristen S , Byun, Jinyoung , Li, Jianrong , Albanes, Demetrius , Bojesen, Stig E. , Johansson, Mattias , Risch, Angela , Bickeböller, Heike , Christiani, David C. , Rennert, Gad , Arnold, Susanne M. , Marchand, Loı̈c Le , Brunnström, Hans , Liu, Geoffrey , Hung, Rayjean J. , Kiemeney, Lambertus A. , Shen, Hongbing , Sun, Ryan , Zienolddiny, Shanbeh , Teare, M. Dawn , Hong, Yun‐Chul , Davies, Michael P.A. , Lazarus, Philip J. , Schabath, Matthew B. , Han, Younghun , Pinney, Susan M. , Willey, James C. , Amos, Christopher I.
No container title available | July 13, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract There is growing evidence showing that sex disparity in lung cancer risk cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotype from a lung cancer cohort including ~ 47,000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 (OR=0.71, p=4.29x10-8); rs79942605 (OR=2.17, p=2.81x10-8); and rs208908 (OR=0.70, p=4.54x10-8), were identified with different risk effect of lung cancer between men and women. Further eQTL and functional annotation analysis suggested rs208908 affect lung cancer risk through differential regulation of CXADR (Coxsackie Virus And Adenovirus Receptor) gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.
Variants in Inflammation Genes Are Implicated in Risk of Lung Cancer in Never Smokers Exposed to Second-hand Smoke
Spitz, Margaret R., Gorlov, Ivan P. , Dong, Qiong, Etzel, Carol J. , Gorlova, Olga Y. , Chang, David W. , Zhang, Di , Cunningham, Julie M. , Yang, Ping , Wu, Xifeng , Amos, Christopher I. , Chen, Wei , Pu, Xia , Wang, Liang
Cancer Discovery | August 26, 2011 | Volume: 1 | Issue: 5 | Pages: 420-429
AbstractLung cancer in lifetime never smokers is distinct from that in smokers, but the role of separate or overlapping carcinogenic pathways has not been explored. We therefore evaluated a comprehensive panel of 11,737 single-nucleotide polymorphisms (SNP) in inflammatory-pathway genes in a discovery phase (451 lung cancer cases, 508 controls from Texas). SNPs that were significant were evaluated in a second external population (303 cases, 311 controls from the Mayo Clinic). An intronic SNP in the ACVR1B gene, rs12809597, was replicated with significance and restricted to those reporting adult exposure to environmental tobacco smoke. Another promising candidate was an SNP in NR4A1, although the replication OR did not achieve statistical significance. ACVR1B belongs to the TGFR-β superfamily, contributing to resolution of inflammation and initiation of airway remodeling. An inflammatory microenvironment (second-hand smoking, asthma, or hay fever) is necessary for risk from these gene variants to be expressed. These findings require further replication, followed by targeted resequencing, and functional validation.Significance: Beyond passive smoking and family history of lung cancer, little is known about the etiology of lung cancer in lifetime never smokers that accounts for about 15% of all lung cancers in the United States. Our two-stage candidate pathway approach examined a targeted panel of inflammation genes and has identified novel structural variants that appear to contribute to risk in patients who report prior exposure to sidestream smoking. Cancer Discovery; 1(5): 420–9. ©2011 AACR.This article is highlighted in the In This Issue feature, p. 367