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The prognostic value of IL10 and TNF alpha functional polymorphisms in premenopausal early-stage breast cancer patients.

Korobeinikova E, Myrzaliyeva D, Ugenskiene R, Raulinaityte D, Gedminaite J, Smigelskas K, Juozaityte E - BMC Genet. (2015)

Bottom Line: Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription.Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017).On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. erikakorobeinikova@gmail.com.

ABSTRACT

Background: Interleukin-10 and tumor necrosis factor α play an important role in breast carcinogenesis. Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription. This study analyzes single nucleotide polymorphisms in interleukin 10 and tumor necrosis factor α genes and their contribution to breast cancer phenotype, lymph node status and survival in a group of young Lithuanian women with early-stage breast cancer patients.

Results: We genotyped 100 premenopausal Eastern European (Lithuanian) patients with stage I-II breast cancer, ≤ 50 years old at the time of diagnosis, for interleukin 10 -592A > C, -819C > T and -1082A > G and tumor necrosis factor α -308G > A single nucleotide polymorphisms in the gene promoter region. We used the polymerase chain reaction, namely a restriction fragment length polymorphism method, for a SNP analysis. All genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the HapMap CEU population. Holders of IL10 -592A > C heterozygous IL10 -592 AC genotype had a higher probability of estrogen receptor positive breast cancer phenotype than homozygous variants (P = 0.017). Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017). Of all the tested single nucleotide polymorphisms, only TNFα -308G > A has revealed a prognostic capability for breast cancer survival. GA genotype carriers, compared to GG, showed a significant disadvantage in progression-free survival (P = 0.005, adjusted hazard ratio (HR) = 4.631, 95 % confidence interval (CI) = 1.587 - 13.512), metastasis-free survival (P = 0.010, HR = 4.708, 95 % CI = 1.445 - 15.345) and overall survival (P = 0.037, HR = 4.829, 95 % CI = 1.098 - 21.243).

Conclusions: According to our data, IL10 -1082A > G, -819 T > C, -592A > C polymorphisms and phased haplotypes have not revealed a prognostic value for breast cancer. On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.

No MeSH data available.


Related in: MedlinePlus

Linkage disequilibrium and haplotype block. Numerical values are given of r2 values, whereas the colors are given to encode D’ (dark grey encodes strong evidence of LD). Block followed the haplotype block definition of solid spine of LD as implemented in the Haploview v.4.1 [22]
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Fig1: Linkage disequilibrium and haplotype block. Numerical values are given of r2 values, whereas the colors are given to encode D’ (dark grey encodes strong evidence of LD). Block followed the haplotype block definition of solid spine of LD as implemented in the Haploview v.4.1 [22]

Mentions: The analysis included 100 primary, young, premenopausal, early stage breast cancer patients. The frequency data for clinical and tumor biological factors is shown in Table 1. All the patients were genotyped for a panel of four SNPs: IL10 -1082A > G, −819 T > C, −592A > C, and TNFα -308G > A. The genotypes were found to be in Hardy-Weinberg equilibrium in all the four SNPs. A strong LD was confirmed for IL10 -819 T allele with IL10 -592A allele and IL10 -819 C allele with IL10 -592C allele (Fig. 1). Our cohort statistically has the same genotype distribution as the HapMap CEU population. The allele and genotype frequencies determined in our study and, for comparison, HapMap CEU population are shown in Table 2.Table 1


The prognostic value of IL10 and TNF alpha functional polymorphisms in premenopausal early-stage breast cancer patients.

Korobeinikova E, Myrzaliyeva D, Ugenskiene R, Raulinaityte D, Gedminaite J, Smigelskas K, Juozaityte E - BMC Genet. (2015)

Linkage disequilibrium and haplotype block. Numerical values are given of r2 values, whereas the colors are given to encode D’ (dark grey encodes strong evidence of LD). Block followed the haplotype block definition of solid spine of LD as implemented in the Haploview v.4.1 [22]
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482272&req=5

Fig1: Linkage disequilibrium and haplotype block. Numerical values are given of r2 values, whereas the colors are given to encode D’ (dark grey encodes strong evidence of LD). Block followed the haplotype block definition of solid spine of LD as implemented in the Haploview v.4.1 [22]
Mentions: The analysis included 100 primary, young, premenopausal, early stage breast cancer patients. The frequency data for clinical and tumor biological factors is shown in Table 1. All the patients were genotyped for a panel of four SNPs: IL10 -1082A > G, −819 T > C, −592A > C, and TNFα -308G > A. The genotypes were found to be in Hardy-Weinberg equilibrium in all the four SNPs. A strong LD was confirmed for IL10 -819 T allele with IL10 -592A allele and IL10 -819 C allele with IL10 -592C allele (Fig. 1). Our cohort statistically has the same genotype distribution as the HapMap CEU population. The allele and genotype frequencies determined in our study and, for comparison, HapMap CEU population are shown in Table 2.Table 1

Bottom Line: Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription.Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017).On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. erikakorobeinikova@gmail.com.

ABSTRACT

Background: Interleukin-10 and tumor necrosis factor α play an important role in breast carcinogenesis. Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription. This study analyzes single nucleotide polymorphisms in interleukin 10 and tumor necrosis factor α genes and their contribution to breast cancer phenotype, lymph node status and survival in a group of young Lithuanian women with early-stage breast cancer patients.

Results: We genotyped 100 premenopausal Eastern European (Lithuanian) patients with stage I-II breast cancer, ≤ 50 years old at the time of diagnosis, for interleukin 10 -592A > C, -819C > T and -1082A > G and tumor necrosis factor α -308G > A single nucleotide polymorphisms in the gene promoter region. We used the polymerase chain reaction, namely a restriction fragment length polymorphism method, for a SNP analysis. All genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the HapMap CEU population. Holders of IL10 -592A > C heterozygous IL10 -592 AC genotype had a higher probability of estrogen receptor positive breast cancer phenotype than homozygous variants (P = 0.017). Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017). Of all the tested single nucleotide polymorphisms, only TNFα -308G > A has revealed a prognostic capability for breast cancer survival. GA genotype carriers, compared to GG, showed a significant disadvantage in progression-free survival (P = 0.005, adjusted hazard ratio (HR) = 4.631, 95 % confidence interval (CI) = 1.587 - 13.512), metastasis-free survival (P = 0.010, HR = 4.708, 95 % CI = 1.445 - 15.345) and overall survival (P = 0.037, HR = 4.829, 95 % CI = 1.098 - 21.243).

Conclusions: According to our data, IL10 -1082A > G, -819 T > C, -592A > C polymorphisms and phased haplotypes have not revealed a prognostic value for breast cancer. On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.

No MeSH data available.


Related in: MedlinePlus