A Single Nucleotide Change in the Mouse Genome Accelerates Breast Cancer Progression
52
Citation
29
Reference
10
Related Paper
Citation Trend
Abstract:
In the growth factor receptor gene FGFR4 the presence of the common single nucleotide polymorphism Arg388 has been associated with progression of various types of cancer including breast cancer. However, a causative relationship is not readily assigned due to genetic heterogeneity in different patient cohorts. To address this issue, we compared the effects of this allele on malignant progression in the WAP-TGFalpha transgenic mouse model of breast cancer. A knock-in strain was generated to introduce an analogous Arg385 allele into the murine FGFR4 gene. Mouse embryonic fibroblasts derived from this strain displayed accelerated cell transformation, with transformed cells exhibiting greater motility and invasive behavior. In the in vivo context of TGFalpha-induced mammary carcinogenesis, tumor development and progression was significantly advanced in tumor mass, size, and onset of pulmonary metastases. Our findings definitively identify the FGFR4 Arg388 allele as a functional prognostic marker for breast cancer progression.Keywords:
Tumor progression
Mendelian inheritance
Phosphoglucomutase
Cite
Citations (48)
Ratón
Cite
Citations (31)
XRCC1 is one of the DNA repair genes, which play an important role in maintains DNA stability via DNA repair by base excision repair and single strand break, As its acts as a scaffold to other repairing proteins. In this study the polymorphism at the codon 194 had been studied in (202) of Iraqi population, distributed in two groups (106) Arab and (96) Kurdish. The alleles for the 194 codon, were investigates by PCR-RFLP techniques. It's found that (94) represented 88.6% Arab individuals carrying the CC dominant homozygous genotype, while (12) individuals represented 11.4% who carry the CT heterozygous genotype, and no one had the recessive TT genotype. In Kurdish group (94) represented 97.9% individuals had the CC dominant homozygous genotype, while only (2) represented 2.1% had the CT heterozygous genotype, also no one had the recessive TT genotype. The allele frequency for the Arab individuals was 0.9434 for the C which encoding for Arginin and 0.0566 for the T allele which encoding for Tryptophan. In Kurdish individuals the frequency of C allele was 0.99 while the frequency of the T allele was 0.01. These results may indicates that the C allele is the most common allele in Iraqi population in both Arab and Kurdish, and there is a slightly high allele frequency were observed in Kurdish may due intermarriage leading to reduce the recessive allele in the population.
XRCC1
Genotype frequency
Cite
Citations (1)
Cite
Citations (33)
Certain single nucleotide polymorphisms (SNPs) in genes like p21 or bcl2 increase susceptibility to breast cancer but it has not, until now, been clear whether common polymorphic variants in the same genes also increase risk in Saudi Arabian population. The aim of this study was therefore to determine whether polymorphisms of p21 or Bcl2 might be associated with an increased risk of breast cancer in Saudi women. p21 (rs733590) C/T SNP was not found to be associated with breast cancer pathogenesis. However, we found that a reverse mutation T/C might be linked with breast cancer occurrence. Bcl2 genotypes were marginally associated overall with breast cancer risk. In addition, the alleles of this gene were significantly associated with risk of breast cancer. The allelic frequency of G was higher (0.68) in patients than in healthy women. AA vs. AG+GG genotype [OR=3.56 (1.24-10.68); P=0.008] was the dominant genotype. It is likely that these genes conferring measurably increased risks of breast cancer in our study population.
SNP
Cite
Citations (7)
Cite
Citations (12)
Cite
Citations (13)
In this study, we tested the hypothesis that single nucleotide polymorphisms (SNPs) of differentiation-associated human gene icb-1 (C1orf38) may be associated with breast cancer susceptibility. A total of 646 women--323 breast cancer cases and just as many controls--were included. Breast cancer patients more frequently carried the homozygous genotype AA of SNP rs1467465 than did healthy women. Analysis of allele positivity revealed that AG or GG genotypes were significantly less frequent in breast cancer patients, suggesting that presence of G allele might have protective effects. Our data suggest that SNP rs1467465 of human gene icb-1 might affect breast cancer susceptibility.
SNP
Cite
Citations (7)
Leprosy is an immunopathology caused by M. leprae; its evolution depends on immunological and genetic aspects of the host. The objective was verifying the relationship between SNPs 2029 and 2258 of the TLR-2 gene and leprosy. Blood samples from 127 individuals were analyzed: 45 patients, being 34 multibacillary (MB) and 11 paucibacillary (PB) and 82 contacts, in the municipalities of the State of Pará-Brazil. SNPs 2029 and 2258 of the TLR-2 gene were genotyped by sequencing on the ABI 3130 Genetic Analyzer (Applied Biosystems), analyzed using Fisher’s exact test. Distribution of SNP 2029 genotypes: all MB individuals presented the C/C genotype and the mutant (C/T) genotype was observed in contacts and PB. Alleles: all MB individuals presented only C allele and the mutant allele (T) was observed in contacts and PB. SNP 2258 genotypes: 79 contacts had G/G genotype and only 3 had G/A genotype, the MB group had only G/G genotype and the PB group was predominant G/G, with only 1 G/A genotype. Alleles: all MB individuals had allele G and the mutant allele (A) was observed in contacts and PB. The association between the SNPs and the susceptibility or protection to leprosy was not observed.
SNP
Genotype frequency
Cite
Citations (0)
Background VTCN1, a T‐cell regulator, belongs to the immunoglobulin superfamily. It is more highly expressed in tumor tissues than in normal tissues, which suggests that it could serve as a tumor‐related agent. We hypothesize the gene variants for this coinhibitory molecule may be associated with the risk of breast cancer, given such gene polymorphisms could affect its related gene expression. Methods Genotypes of the VTCN1 gene variants (rs10754339, rs10801935, and rs3738414) were analyzed in 566 patients with breast cancer and 400 age‐frequency‐matched controls. Results Compared with the major allele, the minor alleles of rs10754339, rs10801935, and rs3738414 did modulate the risk of breast cancer with ORs (95% CI) of 1.42 (1.07–1.89), 1.39 (1.10–1.77), and 0.81 (0.67–0.99), respectively. Those with the rs10754339 genotype AG and rs10801935 AC genotype had significantly increased risks when compared with their major genotypes. However, in rs3738414, the AA genotype had a marginally significant decreased risk compared with its wild genotype. In the haplotype‐based analysis, the GCG allele was associated with significantly increased risk (OR: 1.56, 95% CI: 1.09–2.22) based on the AAG reference. Further analyses of the haplotype pairs showed GCG carriers had a significantly increased risk. Conclusions In this study, the VTCN1 genetic variants (rs10754339, rs10801935, and rs3738414) indicate they could be connected with the risk of breast cancer, which in turn provides indirect evidence that T‐cell immunity could be involved in the development of breast cancer.
Cite
Citations (6)