Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I–II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment.

Implementation of national cancer policy is frequently shaped by medical guidelines. These guidelines often lack detail addressing the intricate care needs of vulnerable groups such as older adults, hindering the potential impact of these policies. To provide an overview of the representation of older adults in European cancer guidelines to identify areas for improvement. A scoping review was conducted using the Arksey and O’Malley framework and Levac et al. extension. The search strategy was developed for grey literature (i.e. guidelines) for the five most prevalent primary malignancies (prostate, breast, colorectal, lung, and urinary bladder) in 29 countries (member states of the European Union, Switzerland, and the UK). Data were extracted by a national expert and at least one other reviewer. A total of 187 guideline reports from 31 jurisdictions were analysed, encompassing general cancer care and selected primary malignancies. The representation of older adults varied by cancer type and region. Dedicated guidelines for older adults were uncommon, with only a few jurisdictions, such as France and Spain, providing age-specific recommendations for certain malignancies. Although some national guidelines addressed older patients, this focus was inconsistent both across different cancers and within the guidelines of the same country. There is limited representation of geriatric oncology across European cancer guidelines. To enhance representative guideline development, there is a call for greater consideration of older adults’ unique needs. Suggestions include further guidance on the implementation of the comprehensive geriatric assessment and consequent treatment across neoadjuvant, adjuvant, and metastatic settings.

Breast cancer is one of the most common oncological diseases among women worldwide. Cell cycle and apoptosis—related genes TP53, BBC3, CCND1 and EGFR play an important role in the pathogenesis of breast cancer. However, the roles of single nucleotide polymorphisms (SNPs) in these genes have not been fully defined. Therefore, this study aimed to analyze the association between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344 and EGFR rs2227983 polymorphisms and breast cancer phenotype and prognosis. For the purpose of the analysis, 171 Lithuanian women were enrolled. Genomic DNA was extracted from peripheral blood; PCR-RFLP was used for SNPs analysis. The results showed that BBC3 rs2032809 was associated with age at the time of diagnosis, disease progression, metastasis and death. CCND1 rs9344 was associated with tumor size, however an association resulted in loss of significance after Bonferroni correction. In survival analysis, significant associations were observed between BBC3 rs2032809 and OS, PFS and MFS. EGFR rs2227983 also showed some associations with OS and PFS (univariate Cox regression analysis). However, the results were in loss of significance (multivariate Cox regression analysis). In conclusion, BBC3 rs2032809 polymorphism was associated with breast cancer phenotype and prognosis. Therefore, it could be applied as potential markers for breast cancer prognosis.

(1) Background. Breast cancer is the leading cancer type among women. Despite convenient diagnostics at early stages, there is a need for continuous monitoring to predict more aggressive or recurring breast cancer forms. The evidence suggests that the detection of genetic biomarkers could help in improving disease management and reduce mortality. Matrix metalloproteinases (MMPs) are a large family of enzymes that perform physiologically relevant functions and have the potential properties to be biomarkers for cancer assessment. We aimed to evaluate the contribution and association of single-nucleotide polymorphisms (SNPs) in MMP genes (MMP1, MMP2, MMP3, MMP7, MMP8, MMP9) with clinicopathological breast-cancer features. (2) Methods. In this study, 100 breast cancer patients were genotyped by polymerase chain reaction–restriction fragment length polymorphism methodology (PCR–RFLP). (3) Results. The presence of the MMP7 rs11568818 A allele was associated with lower chances for poorly differentiated breast cancer. The lower possibility for HER2-positive breast cancer was associated with the presence of the MMP9 rs3918242 C allele. (4) Conclusions. These results indicate that MMP7 rs11568818 and MMP9 rs3918242 are potential biomarkers for the anticipation of breast cancer aggressiveness.

Genetic variations in inflammation- and angiogenesis-related genes may alter the coded protein level and impact the pathogenesis of breast cancer (BC). The present study investigated the association of functional single nucleotide polymorphisms (SNPs) in the VEGFA, IL‑1β, IL‑1α and IL‑6 genes with the early‑stage BC phenotype and survival. Genomic DNA and clinical data were collected for 202 adult Eastern European (Lithuanian) women with primary I‑II stage BC. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Nine VEGFA, IL‑1β, IL‑1α and IL‑6 polymorphisms were analysed. The VEGFA and IL‑6 haplotypes were inferred using Phase software. Patients were prospectively followed‑up for recurrence, occurrence of metastasis and mortality until April 30, 2019. All studied genotypes were in Hardy‑Weinberg equilibrium and had the same distribution as the 1,000 Genomes project Phase 3 dataset for European population. Significant associations of the studied SNPs with clinicopathologic variables were observed between IL‑1α rs1800587 C allele and larger primary tumour size; IL‑6 rs1800797 A allele, rs1800797 GA genotype, rs1800795 C allele, IL‑6 (rs1800797‑re1800795) AC diplotype and hormonal receptor‑positive disease; IL‑6 rs1800797 A allele and HER2 negative status. In univariate Cox survival analysis, IL‑1α rs1800587 CC and IL‑6 rs1800797 GG genotype carriers exhibited worse disease‑free survival (DFS), metastasis‑free survival (MFS) and overall survival (OS). The IL‑6 rs1800795 GG genotype was associated with worse OS. IL‑6 (rs1800797, rs1800795) GG/GG diplotype carriers had shorter MFS and OS. Multivariate Cox survival analysis revealed that the IL‑1α rs1800587 CC genotype was an independent negative prognostic factor for DFS, MFS and OS, and the IL6 GG/GG diplotype was an independent negative prognostic factor for MFS and OS. According to the present study, functional SNPs in the IL‑1α and IL‑6 genes may contribute to the identification of patients at higher risk of BC recurrence, development of metastases and worse OS among early‑stage patients with BC.

Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size (P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status (P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.