Associating CYP2A6 structural variants with ovarian and lung cancer risk in the UK Biobank: replication and extension.

Autor: Langlois AWR; Department of Pharmacology & Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 100 Stokes Street, Toronto, ON, M6J 1H4, Canada., Pouget JG; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 100 Stokes Street, Toronto, ON, M6J 1H4, Canada.; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada., Knight J; Data Science Institute and Medical School, Lancaster University, Lancaster, UK., Chenoweth MJ; Department of Pharmacology & Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 100 Stokes Street, Toronto, ON, M6J 1H4, Canada.; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada., Tyndale RF; Department of Pharmacology & Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. r.tyndale@utoronto.ca.; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 100 Stokes Street, Toronto, ON, M6J 1H4, Canada. r.tyndale@utoronto.ca.; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada. r.tyndale@utoronto.ca.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2024 Mar; Vol. 32 (3), pp. 357-360. Date of Electronic Publication: 2023 Dec 14.
DOI: 10.1038/s41431-023-01518-2
Abstrakt: CYP2A6 is a polymorphic enzyme that inactivates nicotine; structural variants (SVs) include gene deletions and hybrids with the neighboring pseudogene CYP2A7. Two studies found that CYP2A7 deletions were associated with ovarian cancer risk. Using their methodology, we aimed to characterize CYP2A6 SVs (which may be misidentified by prediction software as CYP2A7 SVs), then assess CYP2A6 SV-associated risk for ovarian cancer, and extend analyses to lung cancer. An updated reference panel was created to impute CYP2A6 SVs from UK Biobank array data. Logistic regression models analyzed the association between CYP2A6 SVs and cancer risk, adjusting for covariates. Software-predicted CYP2A7 deletions were concordant with known CYP2A6 SVs. Deleterious CYP2A6 SVs were not associated with ovarian cancer (OR = 1.06; 95% CI: 0.80-1.37; p = 0.7) but did reduce the risk of lung cancer (OR = 0.44; 95% CI: 0.29-0.64; p < 0.0001), and a lung cancer subtype. Replication of known lung cancer associations indicates the validity of array-based SV analyses.
(© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.)
Databáze: MEDLINE
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