Dataset Information

Gene-gene interaction of AhRwith and within the Wntcascade affects susceptibility to lung cancer.

ABSTRACT:

Background

Aberrant Wnt signalling, regulating cell development and stemness, influences the development of many cancer types. The Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated with lung cancer susceptibility.

Aim

To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent.

Methods

Odds ratios (OR) were estimated for genomic variants assigned to the Wnt agonist and the antagonistic genes DKK2, DKK3, DKK4, FRZB, SFRP4 and Axin2. Logistic regression models with variable selection were trained, validated and tested to predict lung cancer, at which other previously identified SNPs that have been robustly associated with lung cancer risk could also enter the model. Furthermore, decision trees were created to investigate variant × variant interaction. All analyses were performed for overall lung cancer and for subgroups.

Results

No genome-wide significant association of AhR/Wnt-genes with overall lung cancer was observed, but within the subgroups of ever smokers (e.g., maker rs2722278 SFRP4; OR = 1.20; 95% CI 1.13-1.27; p = 5.6 × 10^-10) and never smokers (e.g., maker rs1133683 Axin2; OR = 1.27; 95% CI 1.19-1.35; p = 1.0 × 10^-12). Although predictability is poor, AhR/Wnt-variants are unexpectedly overrepresented in optimized prediction scores for overall lung cancer and for small cell lung cancer. Remarkably, the score for never-smokers contained solely two AhR/Wnt-variants. The optimal decision tree for never smokers consists of 7 AhR/Wnt-variants and only two lung cancer variants.

Conclusions

The role of variants belonging to Wnt/AhR-pathways in lung cancer susceptibility may be underrated in main-effects association analysis. Complex interaction patterns in individuals of European descent have moderate predictive capacity for lung cancer or subgroups thereof, especially in never smokers.

SUBMITTER: Rosenberger A

PROVIDER: S-EPMC8805279 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Gene-gene interaction of AhRwith and within the Wntcascade affects susceptibility to lung cancer.

Rosenberger Albert A Muttray Nils N Hung Rayjean J RJ Christiani David C DC Caporaso Neil E NE Liu Geoffrey G Bojesen Stig E SE Le Marchand Loic L Albanes Demetrios D Aldrich Melinda C MC Tardon Adonina A Fernández-Tardón Guillermo G Rennert Gad G Field John K JK Davies Michael P A MPA Liloglou Triantafillos T Kiemeney Lambertus A LA Lazarus Philip P Wendel Bernadette B Haugen Aage A Zienolddiny Shanbeh S Lam Stephen S Schabath Matthew B MB Andrew Angeline S AS Duell Eric J EJ Arnold Susanne M SM Goodman Gary E GE Chen Chu C Doherty Jennifer A JA Taylor Fiona F Cox Angela A Woll Penella J PJ Risch Angela A Muley Thomas R TR Johansson Mikael M Brennan Paul P Landi Maria Teresa MT Shete Sanjay S SS Amos Christopher I CI Bickeböller Heike H

European journal of medical research 20220131 1

<h4>Background</h4>Aberrant Wnt signalling, regulating cell development and stemness, influences the development of many cancer types. The Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated with lung cancer susceptibility.<h4>Aim</h4>To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent.<h4>Methods</h ...[more]

PMID: 35101137

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Dataset Information

Gene-gene interaction of AhRwith and within the Wntcascade affects susceptibility to lung cancer.

Background

Aim

Methods

Results

Conclusions

Publications

Gene-gene interaction of AhRwith and within the Wntcascade affects susceptibility to lung cancer.

Similar Datasets

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