Dataset Information

In silico identification and in vitro expression analysis of breast cancer-related m⁶A-SNPs.

ABSTRACT: Research on m⁶A-associated SNPs (m⁶A-SNPs) has emerged recently due to their possible critical roles in many key biological processes. In this sense, several investigations have identified m⁶A-SNPs in different diseases. In order to gain a more complete understanding of the role that m⁶A-SNPs can play in breast cancer, we performed an in silico analysis to identify the m⁶A-SNPs associated with breast cancer and to evaluate their possible effects. For this purpose, we downloaded SNPs related to breast cancer and a list of m⁶A-SNPs from public databases in order to identify which ones appear in both. Subsequently, we assessed the identified m⁶A-SNPs in silico by expression quantitative trait loci (eQTL) analysis and differential gene expression analysis. We genotyped the m⁶A-SNPs found in the in silico analysis in 35 patients with breast cancer, and we carried out a gene expression analysis experimentally on those that showed differences. Our results identified 981 m⁶A-SNPs related to breast cancer. Four m⁶A-SNPs showed an eQTL effect and only three were in genes that presented an altered gene expression. When the three m⁶A-SNPs were evaluated in the tissue sample of our breast cancer patients, only the m⁶A-SNP rs76563149 located in ZNF354A gene presented differences in allele frequencies and a low gene expression in breast cancer tissues, especially in luminal B HER2+ subtype. Future investigations of these m⁶A-SNPs should expand the study in different ethnic groups and increase the sample sizes to test their association with breast cancer and elucidate their molecular function.

SUBMITTER: Kleinbielen T

PROVIDER: S-EPMC9665143 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

In silico identification and in vitro expression analysis of breast cancer-related m6A-SNPs.

Kleinbielen Tamara T Olasagasti Felix F Azcarate Daniel D Beristain Elena E Viguri-Díaz Amparo A Guerra-Merino Isabel I García-Orad África Á de Pancorbo Marian M MM

Epigenetics 20220829 13

Research on m6A-associated SNPs (m6A-SNPs) has emerged recently due to their possible critical roles in many key biological processes. In this sense, several investigations have identified m6A-SNPs in different diseases. In order to gain a more complete understanding of the role that m6A-SNPs can play in breast cancer, we performed an in silico analysis to identify the m6A-SNPs associated with breast cancer and to evaluate their possi ...[more]

PMID: 35971775

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Project description:BACKGROUND:It has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. A first step included verification of these SNPs as determinants of vitamin D levels. METHODS:The Malmö Diet and Cancer Study included 17,035 women in a prospective cohort. Genotyping was performed and was successful in 4058 nonrelated women from this cohort in which 865 were diagnosed with breast cancer. Levels of vitamin D (25-hydroxyvitamin D) were available for 700 of the breast cancer cases and 643 of unaffected control subjects. SNPs previously associated with vitamin D in GWASs were identified. Logistic regression analyses yielding ORs with 95% CIs were performed to investigate selected SNPs in relation to low levels of vitamin D (below median) as well as to the risk of breast cancer. RESULTS:The majority of SNPs previously associated with levels of vitamin D showed a statistically significant association with circulating vitamin D levels. Heterozygotes of one SNP (rs12239582) were found to have a statistically significant association with a low risk of breast cancer (OR 0.82, 95% CI 0.68-0.99), and minor homozygotes of the same SNP were found to have a tendency towards a low risk of being in the group with low vitamin D levels (OR 0.72, 95% CI 0.52-1.00). Results from stratified analyses showed diverse associations with breast cancer risk for a few of the tested SNPs, depending on whether vitamin D level was high or low. CONCLUSIONS:SNPs associated with vitamin D may also be associated with the risk of breast cancer. Even if such a risk is small, the allele frequency of the SNP variants is high, and therefore the population attributable risk could be substantial. It is also possible that vitamin D levels may interact with genomic traits with regard to breast cancer risk.

Dataset Information

In silico identification and in vitro expression analysis of breast cancer-related m⁶A-SNPs.

Publications

<i>In silico</i> identification and <i>in vitro</i> expression analysis of breast cancer-related m<sup>6</sup>A-SNPs.

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