Cancer is a major health problem and cause of death worldwide that accounted for 7.6 million deaths in 2008, which is projected to continue rising with an estimated 13.1 million deaths in 2030 according to WHO. Breast cancer is the leading cause of cancer-based death among women around the world and its incidence is increasing annually with a similar tendency. In contrast, renal cell carcinoma accounts for only 3% of total human malignancies but it is still the most common type of urological cancer with a high prevalence in elderly men (>60 years of age). There are several factors linked with the development of renal cell cancer only, while others are connected only with breast cancer. Genetic risk factors and smoking are the factors which contribute to carcinogenesis in general. Some evidence exists indicating that vitamin D receptor (VDR) gene polymorphisms are associated with both breast and renal cancer; therefore, we put forward the hypothesis that polymorphisms in the VDR gene may influence both the occurrence risks of these cancers and their prognosis. However, the relationship between VDR polymorphisms and these two specific cancers remains a controversial hypothesis, and consequently needs further confirmation via clinical research together with genetic investigations. Here, we aimed to assess the correlation between the different alleles of VDR gene polymorphisms and renal cell cancer and breast cancer risks separately through a systematic review of the present literature. In contrast, this analysis has revealed that some VDR gene polymorphisms, such as: Bsm1, poly(A), Taq1, Apa1, are to some extent associated with breast cancer risk. Other polymorphisms were found to be significantly associated with renal cell cancer. Namely, they were Fok1, Bsm1, Taq1 and Apa1, which encode proteins participating mainly in proliferation, apoptosis and cell cycle regulation. However, data concerning renal cancer are not sufficient to firmly establish the VDR gene polymorphism association.
Objective. Hydroalcoholic extract of Picrorhiza kurroa and its fractions were subjected to in vitro screening for cytotoxicity; further best active fraction (BAF) obtained was tested against Ehrlich ascites carcinoma (EAC) model in Balb/c mice after its quality control analysis. Methods. Cytotoxicities of all the fractions and mother extract of P. kurroa were determined, using MTT assay on breast cancer (MCF-7, MDA-MB 231) and cervical cancer (HeLa, SiHa) cell lines. Metabolic fingerprinting was developed using HPTLC with quantification of biomarkers (cucurbitacins B and E; betulinic acid; picrosides 1 and 2; and apocynin) in BAF. The EAC tumor-bearing mice were used for in vivo anticancer activity after oral administration (50 mg Kg−1) for 10 days. Results. Cytotoxicity assay of mother extract and its fractions over breast cancer and cervix cancer cell lines showed that dichloromethane (DCM) fraction was most cytotoxic (IC50 36.0–51.0 µg mL−1 at 72 h). Oral administration of DCM fraction showed significant reduction in tumor regression parameters, viable tumor cell count and restoration of hematological parameters may be due to presence of cucurbitacins B and E; betulinic acid; picrosides 1 and 2; and apocynin, as compared to the untreated mice of the control group. Conclusion. The DCM fraction of P. kurroa displayed potent anticancer activity and can be further explored for the development of a potential candidate for cancer therapy.
Estrogen is a key driver of breast cancer and genes involved in its signaling and biosynthesis are crucial in breast cancer progression. In this study, we investigated the role of estrogen signaling and synthesis related genes polymorphism in susceptibility to breast cancer risk in North India population in a case-control approach. We examined the association of single nucleotide polymorphism (SNP) in estrogen receptors, ESR1 (rs2234693) and ESR2 (rs2987983); estrogen biosynthesis enzymes, CYP17A1 (rs743572); and aromatase, CYP19A1 (rs700519) with breast cancer risk. Cases (n = 360) were matched to controls (n = 360) by age, sex, ethnicity, and geographical location. Results provided evidence that all the genetic variants were significantly associated with breast cancer risk among North Indian women. Furthermore, on performing stratified analysis between breast cancer risk and different clinicopathological characteristics, we observed strong associations for menopausal status, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, clinical stage, and histological grade. Our results suggest that these genes could be used as molecular markers to assess breast cancer susceptibility and predicting prognosis in North India population.
Genome-Wide Association Studies (GWAS) have identified Fibroblast growth factor receptor 2 (FGFR2) as a candidate gene for breast cancer with single nucleotide polymorphisms (SNPs) located in intron 2 region as the susceptibility loci strongly associated with the risk. However, replicate studies have often failed to extrapolate the association to diverse ethnic regions. This hints towards the existing heterogeneity among different populations, arising due to differential linkage disequilibrium (LD) structures and frequencies of SNPs within the associated regions of the genome. It is therefore important to revisit the previously linked candidates in varied population groups to unravel the extent of heterogeneity. In an attempt to investigate the role of FGFR2 polymorphisms in susceptibility to the risk of breast cancer among North Indian women, we genotyped rs2981582, rs1219648, rs2981578 and rs7895676 polymorphisms in 368 breast cancer patients and 484 healthy controls by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) assay. We observed a statistically significant association with breast cancer risk for all the four genetic variants (P<0.05). In per-allele model for rs2981582, rs1219648, rs7895676 and in dominant model for rs2981578, association remained significant after bonferroni correction (P<0.0125). On performing stratified analysis, significant correlations with various clinicopathological as well as environmental and lifestyle characteristics were observed. It was evident that rs1219648 and rs2981578 interacted with exogenous hormone use and advanced clinical stage III (after Bonferroni correction, P<0.000694), respectively. Furthermore, combined analysis on these four loci revealed that compared to women with 0–1 risk loci, those with 2–4 risk loci had increased risk (OR = 1.645, 95%CI = 1.152–2.347, P = 0.006). In haplotype analysis, for rs2981578, rs2981582 and rs1219648, risk haplotype (GTG) was associated with a significantly increased risk compared to the common (ACA) haplotype (OR = 1.365, 95% CI = 1.086–1.717, P = 0.008). Our results suggest that intron 2 SNPs of FGFR2 may contribute to genetic susceptibility of breast cancer in North India population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.