Association of Genetic Variants in NF-kB with Susceptibility to Breast Cancer: a Case Control Study

Abstract

Insofar as altered NF-κB signaling stemming from the presence of specific genetic variants in NF-κB gene contribute to cancer pathogenesis, this study evaluated the association between NF-κB rs147574894/I552V, rs148626207/M860T rs3774937 and rs1598859 variants and breast cancer and associated features and complications. This was a retrospective case-control study, which involved 207 women with breast cancer, and 214 cancer-free women who served as controls. NF-κB genotyping was done by real-time PCR. Significantly higher rs3774937 minor allele frequencies (MAF), and lower rs147574894 MAF were seen among breast cancer patients, thereby imparting disease susceptibility and protective nature to these variants, respectively. Significant association of rs3774937 and rs147574894 genotypes with breast cancer was seen under the dominant model. Histological type and grade, molecular type, Her2 positivity and ER+/Her2- correlated positively, while distant metastasis negatively correlated with rs3774937. On the other hand, rs147574894 negatively correlated with histological type and grade, tumor size, Her2 positivity, molecular type, and ER+/Her2-, while rs148626207 correlated positively with histological grade, but negatively with distant metastasis and triple-negative status. Breast cancer-susceptible and -protective 4-locus haplotypes were also identified. This is the first report that addresses the contribution of NF-κB variants to the pathogenesis of breast cancer in Middle Eastern-North African population, and the first to document positive association of rs3774937 with breast cancer.

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach

“…While patients were age-matched to controls, BMI was significantly higher in BC patients, consistent with previous reports documenting BMI as a significant risk factor for BC [42,43]. This was also supported by the findings that a chronic low level of inflammation is associated with obesity, and contributes to BC by damaging the DNA [44]. Moreover, cell proliferation in BC is due to the production of excessive amounts of estrogen and adipokines from fat cells [43,45,46].…”

SaBrcada: Survival Intervals Prediction for Breast Cancer Patients by Dimension Raising and Age Stratification

“…In this study, we combined gene expression and clinical data to establish a reliable survival analysis model, SaBrcada. To enrich the biological information provided, we will integrate characteristics, genetic variants [43], and coexpression network analyses. Based on this improvement, we may extract the determining factors from the black box of the survival analysis tool.…”

RELA mRNA Expression in Epithelial Ovarian Cancer: Correlation with rs11820062 Gene Variant

“…Numerous disorders, including cancer, have been linked to single nucleotide polymorphisms (SNPs) in the NF-κB signaling pathway genes. 14 Most risk alleles predispose to disease are in the non-coding region, with the mechanism of their function largely unknown. Information regarding the association of variants in this gene with the risk of epithelial ovarian cancer is essential, especially since research in Indonesia has never been done.…”