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 (Po0.0001), highly proliferative characteristics (P = 0.0005 for Ki67, Po0.0001 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.

Association of gastrointestinal gland cancer susceptibility loci with esophageal carcinoma among the Chinese Han population: a case–control study

“…However, a recent study reported that CLPTM1L is a commonly overexpressed anti-apoptotic factor in lung cancer [30,32]. Our study and previous research suggest that one SNP can be associated with two or more cancers; for example, rs401681 is associated with many cancers including pancreatic cancer, lung cancer, bladder cancer, and hepatocellular carcinoma [33][34][35]. Further studies are needed to clarify the genetic mechanism of esophageal carcinogenesis by fine mapping the susceptibility region of the variants.…”

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

“…Nothing is known about the function of CCDC170 (coiled-coil domain–containing protein 170), but recurrent ESR1 - CCDC170 rearrangements have been characterized in an aggressive subset of ER + breast cancers 35 . A recent study also showed that higher CCDC170 expression correlated with ER negativity, highly proliferative features and worse clinical outcomes 36 . There are some data to suggest that these genes may cooperatively contribute to the increased proliferative capacity of ER + tumors 20 , and it is tempting to speculate that these may be additional target genes for the candidate causal variants at a subset of the five signals identified here and perhaps responsible for their differential phenotype associations.…”

An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors

“…Associations between CCDC170 polymorphisms and BC susceptibility, progression, and survival have been reported 25,26,48–50. In addition, ESR1 – CCDC170 chromosomal rearrangements have been associated with more aggressive estrogen receptor-positive BCs 51.…”