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. 2020 Jun;9(3):1329-1337.
doi: 10.21037/tau-19-523.

Gene-environment interaction with smoking for increased non-muscle-invasive bladder cancer tumor size

Nadezda Lipunova  1   2   3 , Anke Wesselius  3 , Kar K Cheng  4 , Frederik-Jan van Schooten  5 , Richard T Bryan  1 , Jean-Baptiste Cazier  1   2 , Maurice P Zeegers  1   3
Affiliations

Gene-environment interaction with smoking for increased non-muscle-invasive bladder cancer tumor size

Nadezda Lipunova et al. Transl Androl Urol. 2020 Jun.

Abstract

Background: Urinary bladder cancer (UBC) is one of few cancers with an established gene-environment interaction (GxE) with smoking. However, it is unknown whether the interaction with tobacco use is present non-muscle invasive bladder cancer (NMIBC) and characteristics of prognostic relevance. We aimed to investigate if smoking status and/or smoking intensity interact with the effect of discovered variants on key NMIBC characteristics of tumor grade, stage, size, and patient age within the Bladder Cancer Prognosis Programme (BCPP) cohort.

Methods: Analyzed sample consisted of 546 NMIBC patients with valid smoking data from the BCPP. In a previous genome-wide association study (GWAS), we have identified 61 single nucleotide polymorphisms (SNPs) potentially associated with the NMIBC characteristics of tumor stage, grade, size, and patient age. In the current analysis, we have tested these SNPs for GxE with smoking.

Results: Out of 61 SNPs, 10 have showed suggestion (statistical significance level of P<0.05) for GxE with NMIBC tumor size rs35225990, rs188958632, rs180910528, rs74603364, rs187040828, rs144383242, rs117587674, rs113705641, rs2937268, and chromosome 14:38247577. All SNPs were located across loci of 1p31.3, 3p26.1, 6q14.1, 14q21.1, and 13q14.13. In addition, two of the tested polymorphisms were suggestive for interaction with smoking intensity (chromosome 14:38247577 and rs2937268).

Conclusions: Our study suggests interaction between genetic variance and smoking behavior for increased NMIBC tumor size at the time of diagnosis. Further replication is required to validate these findings.

Keywords: Bladder cancer; SNP; gene-environment interaction (GxE); smoking; tumor size.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-19-523). RTB has contributed to advisory boards for Olympus Medical Systems and Janssen. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Flowchart for data analysis on GxT in the BCPP cohort. GxT, gene-tobacco interaction; BCPP, Bladder Cancer Prognosis Programme; HWE, Hardy-Weinberg equilibrium; SD, standard deviation; IBS, identity by state; PCA, principal component analysis; MAF, minor allele frequency; NMIBC, non-muscle invasive bladder cancer; PCA, principal component analysis; SD, standard deviation; SNP, single nucleotide polymorphism.
Figure 2
Figure 2
Group-specific patterns of significant loci for gene-environment interaction for NMIBC tumour size in the BCPP cohort. Idiogram credit: David Adler, Available online: http://www.pathology.washington.edu/research/cytopages/idiograms/human/. NMIBC, non-muscle invasive bladder cancer; BCPP, Bladder Cancer Prognosis Programme.
Figure S1
Figure S1
eQTL effect of rs144383242 (6q14.1) across multiple tissues (source: GTEx). eQTL, expression quantitative loci; GxE, gene-environment interaction.
Figure S2
Figure S2
Boxplot of an eQTL effect of rs144383242 (6q14.1) in nerve tissue (source: GTEx). eQTL, expression quantitative loci; GxE, gene-environment interaction.
See this image and copyright information in PMC

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