A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.
Author
Summary, in English
Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'- regulatory regions of candidate genes (ESR1, ESR2, PGR and SHBG) or CpG and missense coding SNPs in genes involved in methylation (MBD1, MECP2, DNMT1, MGMT, MTHFR, MTR, MTRR, MTHFD1, MTHFD2, BHMT, DCTD and SLC19A1). Genome-wide searches for genetic risk factors for breast cancers have in general not investigated these SNPs, because of low minor allele frequency or weak haplotype associations.Genotyping was performed using Mass spectrometry-Maldi-Tof in a screening panel of 538 cases and 1067 controls. Potential association to breast cancer was identified for 15 SNPs and one of these SNPs (rs7766585 in ESR1) was found to associate strongly with breast cancer, OR 1.30 (95% CI 1.17-1.45; p-value 2.1x10(-6)), when tested in a verification panel consisting of 3211 unique breast cancer cases and 4223 unique controls from five European biobank cohorts.In conclusion, a candidate gene search strategy focusing on methylation-related SNPs did identify a SNP that associated with breast cancer at high significance.
Department/s
- Clinical Microbiology, Malmö
- Internal Medicine - Epidemiology
- Surgery
- Family Medicine and Clinical Epidemiology
- Division of Clinical Chemistry and Pharmacology
- EpiHealth: Epidemiology for Health
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2011
Language
English
Pages
1689-1698
Publication/Series
International Journal of Cancer
Volume
Dec
Links
Document type
Journal article
Publisher
John Wiley & Sons Inc.
Topic
- Cancer and Oncology
Status
Published
Research group
- Clinical Microbiology, Malmö
- Internal Medicine - Epidemiology
- Surgery
- Family Medicine and Clinical Epidemiology
ISBN/ISSN/Other
- ISSN: 0020-7136