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A candidate CpG SNP approach identifies a breast cancer associated ESR1‐SNP
Author(s) -
Harlid Sophia,
Ivarsson Malin I.L.,
Butt Salma,
Hussain Shehnaz,
Grzybowska Ewa,
Eyfjörd Jorunn Erla,
Lenner Per,
Försti Asta,
Hemminki Kari,
Manjer Jonas,
Dillner Joakim,
Carlson Joyce
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25786
Subject(s) - single nucleotide polymorphism , mtrr , breast cancer , methylenetetrahydrofolate reductase , dna methylation , biology , genetics , snp , candidate gene , cpg site , minor allele frequency , snp genotyping , cancer , mlh1 , allele , genotype , gene , gene expression , dna mismatch repair , colorectal cancer
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 1,067 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 2.1 × 10 −6 ), when tested in a verification panel consisting of 3,211 unique breast cancer cases and 4,223 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.