Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A Large-Scale Genome-Wide Gene-Gene Interaction Study of Lung Cancer Susceptibility in Europeans With a Trans-Ethnic Validation in Asians
Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Health, Harvard T. H. Chan School of Public Health, Massachusetts, Boston; China International Cooperation Center (CICC) for Environment and Human Health, Nanjing Medical University, Nanjing, China.
Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Health, Harvard T. H. Chan School of Public Health, Massachusetts, Boston; China International Cooperation Center (CICC) for Environment and Human Health, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Health, Harvard T. H. Chan School of Public Health, Massachusetts, Boston; China International Cooperation Center (CICC) for Environment and Human Health, Nanjing Medical University, Nanjing, China.
Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Show others and affiliations
2022 (English)In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 17, no 8, p. 974-990Article in journal (Refereed) Published
Abstract [en]

Introduction: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).

Methods: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms (SNPs). Then, the top interactions were further tested by demographically adjusted logistic regression models. Finally, we used the selected interactions to build lung cancer screening models of NSCLC, separately, for never and ever smokers.

Results: With the Bonferroni correction, we identified eight statistically significant pairs of SNPs, which predominantly appeared in the 6p21.32 and 5p15.33 regions (e.g., rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.17, p = 6.57 × 10−13; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.17, p = 2.43 × 10−13; rs2858859HLA-DQA1 and rs9275572HLA-DQA2, ORinteraction = 1.15, p = 2.84 × 10−13; rs2853668TERT and rs62329694CLPTM1L, ORinteraction = 0.73, p = 2.70 × 10−13). Notably, even with much genetic heterogeneity across ethnicities, three pairs of SNPs in the 6p21.32 region identified from the European-ancestry population remained significant among an Asian population from the Nanjing Medical University Global Screening Array project (rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.13, p = 0.008; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.11, p = 5.23 × 10−4; rs3135369BTNL2 and rs9271300HLA-DQA1, ORinteraction = 0.89, p = 0.006). The interaction-empowered polygenetic risk score that integrated classical polygenetic risk score and G × G information score was remarkable in lung cancer risk stratification.

Conclusions: Important G × G interactions were identified and enriched in the 5p15.33 and 6p21.32 regions, which may enhance lung cancer screening models.

Place, publisher, year, edition, pages
Elsevier, 2022. Vol. 17, no 8, p. 974-990
Keywords [en]
Cancer risk, Gene-gene interaction, Genetic screening model, GWAS, Lung cancer, Single nucleotide polymorphism
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-203216DOI: 10.1016/j.jtho.2022.04.011ISI: 000863994300009PubMedID: 35500836Scopus ID: 2-s2.0-85130893494OAI: oai:DiVA.org:umu-203216DiVA, id: diva2:1728139
Funder
NIH (National Institutes of Health)Available from: 2023-01-17 Created: 2023-01-17 Last updated: 2023-05-22Bibliographically approved

Open Access in DiVA

fulltext(2360 kB)273 downloads
File information
File name FULLTEXT01.pdfFile size 2360 kBChecksum SHA-512
caa5ad5087ff96fe2d4dd889c3c38b712e55998915bab124135476424a8528f3e2b2d26356357802cfbb19a42c2b2b27f6df0d6b8919080b12dce3ad9b554be4
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Behndig, Annelie F.Johansson, Mikael

Search in DiVA

By author/editor
Behndig, Annelie F.Johansson, Mikael
By organisation
Section of MedicineOncology
In the same journal
Journal of Thoracic Oncology
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 275 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 191 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf