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Asta Försti

Publications and source records attributed to Asta Försti.

29 records · Page 2Linked to original sources
PubMed2005

Determination of allele frequency in pooled DNA: comparison of three PCR-based methods.

Determination of allele frequency in pooled DNA samples is a powerful and efficient tool for large-scale association studies. In this study, we tested and compared three PCR-based methods for accuracy, reproducibility, cost, and convenience. The methods compared were: (i) real-time PCR with allele-specific primers, (ii) real-time PCR with allele-specific TaqMan probes, and (iii) quantitative sequencing. Allele frequencies of three single nucleotide polymorphisms in three different genes were estimated from pooled DNA. The pools were made of genomic DNA samples from 96 cases with basal cell carcinoma of the skin and 96 healthy controls with known genotypes. In this study, the allele frequency estimation made by real-time PCR with allele-specific primers had the smallest median deviation (MD) from the real allele frequency with 1.12% (absolute percentage points) and was also the cheapest method. However; this method required the most time for optimization and showed the highest variation between replicates (SD = 6.47%). Quantitative sequencing, the simplest method, was found to have intermediate accuracies (MD = 1.44%, SD = 4.2%). Real-time PCR with TaqMan probes, a convenient but very expensive method, had an MD of 1.47% and the lowest variation between replicates (SD = 3.18%).

Costs and Cost Analysis↗
PubMed2004

Polymorphisms and haplotype structures in genes for transforming growth factor beta1 and its receptors in familial and unselected breast cancers.

Alterations in TGF-beta signaling appear to be associated with an altered risk of developing cancer, including breast cancer. We carried out a case-control study on 8 polymorphisms, including 5 in the TGF-beta1 gene (G-800A, C-509T, Leu10-->Pro, Arg25-->Pro and Thr263-->Ile), a polyalanine polymorphism (9A-->6A) in the TGF-betaRI gene and 2 (G-875A and A-364G) in the TGF-betaRII gene, using samples from 2 different populations, Polish familial and Finnish unselected breast cancer cases, together with ethnically and geographically matched controls. Additionally, familial breast cancer cases with respective controls from Sweden and Germany were studied in the Leu10-->Pro polymorphism, making the total number of familial cases 659. Allele, genotype and haplotype analysis on the TGF-beta1 gene as well as an analysis of the combinations of genotypes of the TGF-beta1 and its receptor genes in each individual were performed. Population differences in the allele and genotype distributions were found from 5 of the polymorphisms and 3 common haplotypes from the TGF-beta1 gene between the Finnish and other populations. However, no statistically significant difference between the breast cancer and healthy control groups was found for any of the 8 polymorphisms nor did the haplotype or genotype combination analysis reach statistical significance. Thus, none of the studied polymorphisms from the TGF-beta1 and its receptor genes was found to influence significantly susceptibility to breast cancer. The possible contribution of 6A/6A homozygosity in the TGF-betaRI gene to breast cancer needs to be confirmed in an independent study.

Activin Receptors, Type I↗
PubMed2004

The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer.

The insulin-like growth factor 1 (IGF-1) pathway plays an important role in regulating cell proliferation, differentiation and apoptosis. IRS1, IRS2 and SHC1 are the key mediators for the downstream pathway processes. Genetic variation within these genes may lead to altered signalling. We screened IRS1, IRS2 and SHC1 for published coding region polymorphisms and choose five of them, IRS1 Ala804Ala and Gly972Arg, IRS2 Cys816Cys and Gly1057Asp and SHC1 Met300Val, for further analysis. We studied the association of the polymorphisms with breast cancer risk using a case-control design with Polish familial breast cancer cases and respective controls. For the polymorphisms in IRS1 and IRS2 no differences in the allele, genotype or haplotype distributions could be detected between the case and control subjects. Carriers of the variant allele of the SHC1 polymorphism were at decreased risk of breast cancer (OR 0.54, 95% CI 0.32-0.90, P = 0.016). A non-significant trend for a protective effect of the SHC1 Val300 allele was also seen in an independent population consisting of German familial breast cancer cases and matched controls. The joint analysis after Mantel-Haenzsel adjustment of the two populations gave an OR of 0.62 (95% CI 0.41-0.93, P = 0.02) for the SHC1 Val300 carriers. A stronger effect was detected in women diagnosed below the age of 50 (OR 0.54, 95% CI 0.32-0.89, P = 0.01). A genotype combination analysis of the non-synonymous polymorphisms in the IRS1, IRS2 and SHC1 genes did not show any effect on breast cancer risk.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Single nucleotide polymorphisms in breast cancer.

A limited number of genes have been identified that explain heritable risks of breast cancer (BC). We searched for low-penetrant genes in an association study using two populations: 223 Finnish unselected patients and 172 Polish familial cases, both with locally collected healthy controls. Candidate genes included DNA repair genes, methylenetetrahydrofolate reductase (MTHFR) and cyclin D1 genes. The frequencies for single nucleotide polymorphisms (SNPs) were measured in the following genes: NBS1, XPC, XPD, XRCC1, XRCC3, MTHFR, and cyclin D1. Odds ratios (ORs) were calculated to the wild-type genotype. The positive findings in the Finnish series were repeated in the Polish series. Significant findings among Finns were associations to XPC exon 15, XPD exon 10 and XRCC3 exon 7, the latter of borderline significance. None of these results could be repeated in the Polish series. The XPC result among Finns was probably an artifact of the control group deviating from the Hardy-Weinberg Equilibrium (HWE). The attempt to repeat the result for the XPD polymorphism among Poles was probably not valid because the control group deviated from the HWE. We conclude that within statistical power of the present study, none of the tested polymorphisms associated with BC, with the probable exception of XPD.

Breast Neoplasms↗
PubMed2003

Single nucleotide polymorphisms in the XPG gene: determination of role in DNA repair and breast cancer risk.

In this study we determined the effect of single nucleotide polymorphisms in the XPG gene on DNA repair and breast cancer susceptibility. Ninety individuals, with previously studied DNA repair rate at 24 hr of 2 types of UV-specific cyclobutane pyrimidines dimers (CPDs) in skin were genotyped for XPG polymorphism at codon 1104 (exon 15 G>C; Asp > His). The repair rate of TT=C dimer was similar in both wild-type GG homozygotes and GC heterozygotes, whereas, for TT=T, dimer repair was non-significantly (Student's t-test, p = 0.34) lower in GC heterozygotes than wild-type GG homozygotes. Genotyping of 220 breast cancer cases and 308 controls for the same single nucleotide polymorphism in exon 15 of the XPG gene exhibited marginally significant increased frequency of the variant allele (chi(2) 3.84, p = 0.05; OR 1.33, 95% CI 1.0-1.8) in cases (C-allele 0.29) compared to controls (C-allele 0.24). Combined heterozygote and variant homozygote genotype frequency was also higher in cases than controls (chi(2) 4.79, p = 0.03; OR 1.50, 95%CI 1.04-2.16).

Adult↗
PubMed2003

Polymorphisms in the estrogen receptor beta gene and risk of breast cancer: no association.

Polymorphisms in the estrogen receptor beta (ERbeta) gene may influence the cellular growth regulating effects of estradiol. In this first association study about breast cancer risk and polymorphisms in the ERbeta gene we have screened 219 Finnish sporadic breast cancer cases and 248 ethnically matched male controls. No difference in the allele distribution of the six studied polymorphisms was found between the breast cancer and control groups.

Breast Neoplasms↗
PubMed2003

Human estrogen receptor beta 548 is not a common variant in three distinct populations.

Several isoforms of estrogen receptor (ER) beta (also known as NR3A2) have been reported, including variants with different N-terminal ends. In rodents, two in-frame initiation codons (ATGs) are used to produce proteins of 530 and 549 amino acids, respectively. In humans, the upstream ATG is out of frame in all clones reported, until recently, when human clones with an extra A-T base pair placing the upstream ATG in frame were reported. The authors suggested that this could represent a novel polymorphism in the ERbeta gene. Because human ERbeta548 (hERbeta548) and hERbeta530 display different functional characteristics in vitro, it is of interest to determine if this variant constitutes a polymorphism in human populations. We therefore determined the frequency of this novel isoform in several populations including African (n = 96), Caucasian (n = 100), and Asian (n = 128) subjects using denaturing HPLC. We did not detect any alleles that correspond to hERbeta548 in these samples or in additional samples of heterogeneous origin. It is concluded that hERbeta548 is not a common variant in Africans, Caucasians, or Asians.

Alleles↗
PubMed2002

Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer.

Ovarian steroids are one of the strongest risk factors for breast cancer. Sex hormone-binding globulin (SHBG) binds and transports sex steroids in the blood, regulating their bioavailable fraction and access to target cells. It can also inhibit the estradiol-induced proliferation of breast cancer cells through its membrane receptor. Three coding-region polymorphisms, which lead to an amino acid change, have been reported. We studied the influence of these three polymorphisms on breast cancer risk in three different populations: Polish familial breast cancer cases, 27% of them carrying a BRCA1/BRCA2 mutation, Nordic familial and sporadic breast cancer cases. The reported G to A polymorphism in exon 1 was not found in the 423 analyzed samples. Instead, we found a C to T transition causing an arg to cys amino acid change within the same codon in one Polish breast cancer patient and her daughter. Both of them were heterozygotes for the exon 8 G to A polymorphism as well. They were diagnosed for bilateral breast cancer and carried a BRCA1 mutation (5382insC). Analysis of the tumor samples showed that they had lost the wild-type allele both at exons 1 and 8 of the SHBG gene. Analysis of the other Polish samples showed no correlation of the exon 8 polymorphism to breast cancer, bilateral breast cancer, BRCA1/BRCA2 mutations or age at diagnosis. No association of the exon 8 polymorphism with breast cancer in the Nordic familial or sporadic cases was found. The C to T polymorphism located in exon 4 was rare in all the studied populations (overall allele frequency 0.011). However, in each of the study populations there was a trend for a lower variant allele frequency in cancer cases than in controls. Variant allele frequency in all the breast cancer cases was significantly lower than in all the controls (chi(2) = 5.27, P-value 0.02; odds ratio = 0.23, 95% confidence interval 0.05-0.84).

Adult↗