Fine mapping of chromosome 5p15.33 identifies novel lung cancer susceptibility loci in Han Chinese. Int J Cancer 2017 Aug 01;141(3):447-456
Date
03/24/2017Pubmed ID
28335076DOI
10.1002/ijc.30702Scopus ID
2-s2.0-85019108967 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
Genome-wide association studies in European and Asian populations have consistently identified chromosome 5p15.33 as a lung cancer susceptibility region. To investigate further the genetic architecture of common variants in this region, we conducted a two-stage fine-mapping analysis discovered by targeted resequencing of 200 cases and 300 controls individually, and validated in multiethnic lung cancer Genome wide association studies (GWASs) with 12,843 cases and 12,639 controls. Two independent variants were identified in approximate conditional analysis with GCTA and consistently validated in lung cancer GWASs in both Asian and European populations. These were rs10054203 in TERT (resequencing: OR = 1.69, p = 2.70 × 10-4 ; validation: OR = 1.34, p = 2.10 × 10-23 for Asian, and OR = 1.09, p = 6.00 × 10-3 for European), and rs397640 in CLPTM1L (resequencing: OR = 0.37, p = 1.19 × 10-4 ; validation: OR = 0.75, p = 5.89 × 10-8 for Asian, and OR = 0.90, p = 2.40 × 10-2 for European). Expression quantitative trait loci analysis showed the risk allele (C) of rs10054203 was significantly associated with lower mRNA expression of CTD-2245Ef15.3 (p = 0.019) and Tubulin Polymerization-Promoting Protein (TPPP, p = 0.031) in 167 lung tissues. In conclusion, in this largest and first resequencing-based fine-mapping analysis of 5p15.33 region in Han Chinese, we identified two novel variants associated with lung cancer susceptibility. Further validation studies and functional work is required to confirm the roles of the newly discovered variants.
Author List
Dong J, Cheng Y, Zhu M, Wen Y, Wang C, Wang Y, Geng L, Shen W, Liu J, Li Z, Zhang J, Ma H, Dai J, Jin G, Hu Z, Shen HAuthor
Jing Dong PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorCase-Control Studies
Chromosome Mapping
Chromosomes, Human, Pair 5
Female
Follow-Up Studies
Genetic Predisposition to Disease
Genome-Wide Association Study
High-Throughput Nucleotide Sequencing
Humans
Lung Neoplasms
Male
Membrane Proteins
Middle Aged
Neoplasm Proteins
Neoplasm Staging
Polymorphism, Single Nucleotide
Prognosis
Telomerase