Dataset Information

Association of DEAR1 Tagging Single Nucleotide Polymorphisms With Breast Cancer in a Sample of Colombian Population: A Case Control Study.

ABSTRACT: Purpose:Ubiquitin ligase genes can act as oncogenes or tumor suppressor genes. They play a role in various diseases, including development and progression of breast cancer; the objective of this study was to evaluate the association of common variants in the ductal-epithelium-associated RING chromosome 1 (DEAR1) gene with breast cancer risk in a sample of Colombian population. Methods:We carried out a case-control study to investigate associations of variants in DEAR1 with breast cancer in women from Colombia. Single nucleotide polymorphisms (SNPs) rs584298, rs2927970, rs59983645, and rs599167 were genotyped in 1022 breast cancer cases and 1023 healthy controls using the iPLEX® and Kompetitive Allele Specific PCR (polymerase chain reaction) (KASP) method. The associations between SNPs and breast cancer were examined by conditional logistic regression. The associations between SNPs and epidemiological/histopathological variables were examined by multinomial logistic regression. Results:Associations were found between tag SNPs and breast cancer adjusted for the epidemiological risk factors rs584298 genotypes AG and GG (P?=?.048 and P?=?.004, respectively). The analysis of the disease characteristics showed that SNP rs584298 (genotype AG) (P?=?.015) shows association with progesterone receptor (PR) status and (genotype AA) (P?=?.048) shows association with human epidermal growth factor receptor 2 (HER2) status. Conclusions:The SNP rs584298 in DEAR1 showed associations with breast cancer and the expression of HER2 receptor; when this receptor is amplified, the result is aggressive tumoral subtype and expression of PR receptor that is associated with high-proliferative tumor grade. Validation of this SNP is important to establish whether this variant or the tagged variant is the cause for the risk association showed.

SUBMITTER: Beltran AP

PROVIDER: S-EPMC7172001 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of <i>DEAR1</i> Tagging Single Nucleotide Polymorphisms With Breast Cancer in a Sample of Colombian Population: A Case Control Study.

Beltrán Angela P AP Benitez Edgar E Rondon Martin M Ariza Yeimy V YV Aristizabal Fabio A FA Briceño Ignacio I

Breast cancer : basic and clinical research 20200420

<h4>Purpose</h4>Ubiquitin ligase genes can act as oncogenes or tumor suppressor genes. They play a role in various diseases, including development and progression of breast cancer; the objective of this study was to evaluate the association of common variants in the <i>ductal-epithelium-associated RING chromosome 1</i> (<i>DEAR1</i>) gene with breast cancer risk in a sample of Colombian population.<h4>Methods</h4>We carried out a case-control study to investigate associations of variants in <i>D ...[more]

PMID: 32341648

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Project description:BackgroundMicroRNAs (miRNAs) regulate gene expression and influence cancer. Primary transcripts of miRNAs (pri-miRNAs) are poorly annotated and little is known about the role of germline variation in miRNA genes and breast cancer (BC). We sought to identify germline miRNA variants associated with BC risk and tumor subtype among African-American (AA) women.MethodsUnder the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, genotyping and imputed data from four studies on BC in AA women were combined into a final dataset containing 224,188 miRNA gene single nucleotide polymorphisms (SNPs) for 8350 women: 3663 cases and 4687 controls. The primary miRNA sequence was identified for 566 miRNA genes expressed in Encyclopedia of DNA Elements (ENCODE) Tier 1 cell types and human pancreatic islets. Association analysis was conducted using logistic regression for BC status overall and by tumor subtype.ResultsA novel BC signal was localized to an 8.6-kb region of 17q25.3 by four SNPs (rs9913477, rs1428882938, rs28585511, and rs7502931) and remained statistically significant after multiple test correction (odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.26-1.65; p = 3.15 × 10-7; false discovery rate (FDR) = 0.03). These SNPs reside in a genomic location that includes both the predicted primary transcript of the noncoding miRNA gene MIR3065 and the first intron of the gene for brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2). Furthermore, miRNA-associated SNPs on chromosomes 1p32.3, 5q32, and 3p25.1 were the strongest signals for hormone receptor, luminal versus basal-like, and HER2 enrichment status, respectively. A second phase of genotyping (1397 BC cases, 2418 controls) that included two SNPs in the 8.6-kb region was used for validation and meta-analysis. While neither rs4969239 nor rs9913477 was validated, when meta-analyzed with the original dataset their association with BC remained directionally consistent (OR = 1.29, 95% CI = 1.16-1.44 (p = 4.18 × 10-6) and OR = 1.33, 95% CI = 1.17-1.51 (p = 1.6 × 10-5), respectively).ConclusionGermline genetic variation indicates that MIR3065 may play an important role in BC development and heterogeneity among AA women. Further investigation to determine the potential functional effects of these SNPs is warranted. This study contributes to our understanding of BC risk in AA women and highlights the complexity in evaluating variation in gene-dense regions of the human genome.

Dataset Information

Association of DEAR1 Tagging Single Nucleotide Polymorphisms With Breast Cancer in a Sample of Colombian Population: A Case Control Study.

Publications

Association of <i>DEAR1</i> Tagging Single Nucleotide Polymorphisms With Breast Cancer in a Sample of Colombian Population: A Case Control Study.

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