title: C6ORF97-ESR1 breast cancer susceptibility locus: influence on progression and survival in breast cancer patients.
abstract: Genome-wide association studies have identified a single-nucleotide polymorphism (SNP) to be associated with an increased risk of breast cancer. The biology of one of the susceptibility locus C6ORF-ESR1 and whether it also contributes to progression of established disease has not yet been ascertained. We examined the association of rs2046210 and its six linkage disequilibrium SNPs with clinicopathological characteristics, prognosis, and gene expression levels of ESR1 and the C6ORFs (C6ORF97:CCDC170, C6ORF211, C6ORF96:RMND1) in 344 breast cancer tissue samples and 253 corresponding samples of adjacent normal tissue. Tumor genotypes with homozygous risk alleles were more frequent than normal tissues. The tumor genotypes of rs2046210 and rs6929137 with homozygous risk alleles showed worse relapse-free survival (RFS, P=0.038 and P=0.031, respectively), whereas no notable associations were observed with either clinicopathological characteristics or expression of the peripheral genes. Higher C6ORF97 expression correlated with ER negativity (P<0.0001), highly proliferative characteristics (P=0.0005 for Ki67, P<0.0001 for nuclear grade) and worse RFS in the ER+/HER2- cohort (P=0.013), whereas the other two C6ORFs showed the inverse associations. Furthermore, C6ORF97 showed significant worse prognostic values especially in luminal B subtype in the publically available data sets. rs2046210 and the upstream gene C6ORF97 might have substantial roles not only in carcinogenesis but also in progression toward a more aggressive phenotype in breast cancer patients, which suggests that functional studies of this locus are imperative.
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamamoto-Ibusuki
authors.affiliation: 1] Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan [2] Department of Molecular Targeting Therapy for Breast Cancer, Graduate School of Medical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: 1] Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan [2] Department of Molecular Targeting Therapy for Breast Cancer, Graduate School of Medical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sueta
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tomiguchi
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeshita
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C000599973:CCDC170 protein, human; D002352:Carrier Proteins; D047628:Estrogen Receptor alpha