A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.

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.

• Författare: Sophia Harlid; Malin I L Ivarsson; Salma Butt; Shehnaz Hussain; Ewa Grzybowska; Jorunn Erla Eyfjörd; Per Lenner; Asta Försti; Kari Hemminki; Jonas Manjer; Joakim Dillner; Joyce Carlson
• Avdelning/ar: Klinisk mikrobiologi, Malmö; Internmedicin - epidemiologi; Kirurgi; Allmänmedicin och klinisk epidemiologi; Avdelningen för klinisk kemi och farmakologi; EpiHealth: Epidemiology for Health; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 1689-1698
• Publikation/Tidskrift/Serie: International Journal of Cancer
• Volym: Dec
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/21105050?dopt=Abstract; http://dx.doi.org/10.1002/ijc.25786
• Dokumenttyp: Artikel i tidskrift
• Förlag: John Wiley & Sons Inc.
• Ämne: Cancer and Oncology
• Status: Published
• Forskningsgrupp: Clinical Microbiology, Malmö; Internal Medicine - Epidemiology; Surgery; Family Medicine and Clinical Epidemiology
• ISBN/ISSN/Övrigt: ISSN: 0020-7136