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

Nadezda Lipunova, Anke Wesselius, Kar K Cheng, Frederik-Jan van Schooten, Richard T Bryan, Jean-Baptiste Cazier, Maurice P Zeegers

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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.

Original languageEnglish
Pages (from-to)1329-1337
Number of pages9
JournalTranslational Andrology and Urology
Issue number3
Publication statusPublished - 30 Jun 2020


  • Bladder cancer
  • SNP
  • gene-environment interaction (GxE)
  • smoking
  • tumor size


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