A Case-Only Genome-Wide Interaction Study of Smoking and Bladder Cancer Risk: Results from the COBLAnCE Cohort

Maryam Karimi, Sebastian Mendez-Pineda, Hélène Blanché, Anne Boland, Céline Besse, Jean François Deleuze, Xiang Yu Meng, Nanor Sirab, Karine Groussard, Thierry Lebret, Julia Bonastre, Yves Allory, François Radvanyi, Simone Benhamou, Stefan Michiels

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Bladder cancer (BC) is the 6th most common cancer worldwide, with tobacco smoking considered as its main risk factor. Accumulating evidence has found associations between genetic variants and the risk of BC. Candidate gene-environment interaction studies have suggested interactions between cigarette smoking and NAT2/GSTM1 gene variants. Our objective was to perform a genome-wide association case-only study using the French national prospective COBLAnCE cohort (COhort to study BLAdder CancEr), focusing on smoking behavior. The COBLAnCE cohort comprises 1800 BC patients enrolled between 2012 and 2018. Peripheral blood samples collected at enrolment were genotyped using the Illumina Global Screening Array with a Multi-Disease drop-in panel. Genotyping data (9,719,614 single nucleotide polymorphisms (SNP)) of 1674, 1283, and 1342 patients were analyzed for smoking status, average tobacco consumption, and age at smoking initiation, respectively. A genome-wide association study (GWAS) was conducted adjusting for gender, age, and genetic principal components. The results suggest new candidate loci (4q22.1, 12p13.1, 16p13.3) interacting with smoking behavior for the risk of BC. Our results need to be validated in other case-control or cohort studies.

    Original languageEnglish
    Article number4218
    JournalCancers
    Volume15
    Issue number17
    DOIs
    Publication statusPublished - 1 Sept 2023

    Keywords

    • bladder cancer
    • case-only design
    • genome-wide association study
    • smoking

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