Limits...
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

Kaplan–Meier curves for progression-free survival of TNFα -308G > A polymorphism GG and GA genotypes
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Kaplan–Meier curves for progression-free survival of TNFα -308G > A polymorphism GG and GA genotypes

Mentions: In the median follow-up time of 70 months (range 28–157), progression was observed for 24 patients. 76 cases were censored. Of those who progressed, 20 had distant metastases. 14 patients with progressive disease died, all due to cancer related death. The data of Cox’s proportional hazards regression analysis is shown in Table 4. Kaplan-Meier and Cox's regression analysis did not reveal any significant relationships between the analyzed IL10 -1082A > G, −819 T > C, −592A > C SNPs and phased haplotypes and PFS, MFS and OS in our study. Cox’s regression analysis of TNFα -308G > A SPN has shown a significant disadvantage of GA genotype vs. two others in PFS (P = 0.020, hazard ratio (HR) = 3.049, 95 % CI = 1.195-7.778) and MFS (P = 0.045, HR = 2.819, 95 % CI = 1.021-7.780). During a further analysis of this SNP, we evaluated only the major GG genotype vs. heterozygous GA because of a small number of AA genotypes in our population. GG genotype of the TNFα -308G > A polymorphism was significantly associated with a longer PFS by carrying out the Kaplan-Meier analysis, which is graphically shown in Fig. 2 (P = 0.014). Mean PFS was 119 months in GG genotype group (95 % CI 108–129) vs. 86 months in GA genotype group (95 % CI 56–116).Table 4


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)

Kaplan–Meier curves for progression-free survival of TNFα -308G > A polymorphism GG and GA genotypes
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Kaplan–Meier curves for progression-free survival of TNFα -308G > A polymorphism GG and GA genotypes
Mentions: In the median follow-up time of 70 months (range 28–157), progression was observed for 24 patients. 76 cases were censored. Of those who progressed, 20 had distant metastases. 14 patients with progressive disease died, all due to cancer related death. The data of Cox’s proportional hazards regression analysis is shown in Table 4. Kaplan-Meier and Cox's regression analysis did not reveal any significant relationships between the analyzed IL10 -1082A > G, −819 T > C, −592A > C SNPs and phased haplotypes and PFS, MFS and OS in our study. Cox’s regression analysis of TNFα -308G > A SPN has shown a significant disadvantage of GA genotype vs. two others in PFS (P = 0.020, hazard ratio (HR) = 3.049, 95 % CI = 1.195-7.778) and MFS (P = 0.045, HR = 2.819, 95 % CI = 1.021-7.780). During a further analysis of this SNP, we evaluated only the major GG genotype vs. heterozygous GA because of a small number of AA genotypes in our population. GG genotype of the TNFα -308G > A polymorphism was significantly associated with a longer PFS by carrying out the Kaplan-Meier analysis, which is graphically shown in Fig. 2 (P = 0.014). Mean PFS was 119 months in GG genotype group (95 % CI 108–129) vs. 86 months in GA genotype group (95 % CI 56–116).Table 4

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