Targeted Resequencing of the Coding Sequence of 38 Genes Near Breast Cancer GWAS Loci in a Large Case-Control Study.
Bolla, Manjeet K
Conroy, Don M
Ostrander, Elaine A
Cancer Epidemiol Biomarkers Prev
American Association for Cancer Research (AACR)
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Decker, B., Allen, J., Luccarini, C., Pooley, K., Shah, M., Bolla, M. K., Wang, J., et al. (2019). Targeted Resequencing of the Coding Sequence of 38 Genes Near Breast Cancer GWAS Loci in a Large Case-Control Study.. Cancer Epidemiol Biomarkers Prev, 28 (4), 822-825. https://doi.org/10.1158/1055-9965.EPI-18-0298
BACKGROUND: Genes regulated by breast cancer risk alleles identified through genome-wide association studies (GWAS) may harbor rare coding risk alleles. METHODS: We sequenced the coding regions for 38 genes within 500 kb of 38 lead GWAS SNPs in 13,538 breast cancer cases and 5,518 controls. RESULTS: Truncating variants in these genes were rare, and were not associated with breast cancer risk. Burden testing of rare missense variants highlighted 5 genes with some suggestion of an association with breast cancer, although none met the multiple testing thresholds: MKL1, FTO, NEK10, MDM4, and COX11. Six common alleles in COX11, MAP3K1 (two), and NEK10 (three) were associated at the P < 0.0001 significance level, but these likely reflect linkage disequilibrium with causal regulatory variants. CONCLUSIONS: There was no evidence that rare coding variants in these genes confer substantial breast cancer risks. However, more modest effect sizes could not be ruled out. IMPACT: We tested the hypothesis that rare variants in 38 genes near breast cancer GWAS loci may mediate risk. These variants do not appear to play a major role in breast cancer heritability.
Humans, Breast Neoplasms, Genetic Predisposition to Disease, Case-Control Studies, Gene Frequency, Female, Genome-Wide Association Study
Cancer Research Uk (None)
Cancer Research UK (CRUK-A16563)
External DOI: https://doi.org/10.1158/1055-9965.EPI-18-0298
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280350