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The -553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women.

Rykala J, Przybylowska K, Majsterek I, Pasz-Walczak G, Sygut A, Dziki A, Kuna P - Arch Med Sci (2014)

Bottom Line: Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples.Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23-5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49-6.99) (p = 0.002).Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Barlicki Hospital, Medical University of Lodz, Poland.

ABSTRACT

Introduction: Fibroblast growth factor-2 (FGF2) is an important signalling molecule contributing to angiogenesis, tumour growth and progression and its expression is implicated in breast cancer (BC) development. We investigated whether -553 T/A FGF2 gene polymorphism is associated with the risk and progression of BC in Polish women.

Material and methods: The -553 T/A polymorphism was genotyped in 230 breast cancer patients and 245 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples.

Results: The T/A genotypes (OR = 2.12, 95% CI: 1.20-3.74) (p = 0.08) and the combined heterozygotes T/A and homozygote A/A (OR = 2.18, 95% CI: 1.24-3.83) (p = 0.006) had an increased risk of BC. The median FGF2 levels in the tumours of A allele carriers were significantly increased compared to T/T patients, whereas in serum FGF2 levels were hardly altered among different genotype carriers. Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23-5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49-6.99) (p = 0.002). Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients.

Conclusions: Our study shows for the first time that the -553 T/A FGF2 gene polymorphism may be associated with a risk of BC developing and progression in Polish women and may have prognostic value for the assessment of BC high-risk groups.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier disease-free survival (DFS) curves for breast cancer patients related to genotypes of –553 T/A FGF2 gene polymorphism; p = 0.0119; HR: 0.4516 (95% CI: 0.2119–0.9624)
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Figure 0001: Kaplan-Meier disease-free survival (DFS) curves for breast cancer patients related to genotypes of –553 T/A FGF2 gene polymorphism; p = 0.0119; HR: 0.4516 (95% CI: 0.2119–0.9624)

Mentions: We assessed whether the -553 T/A polymorphism was associated with various clinical parameters such as histological grade, tumour size, lymph node, ER, PR and HER2 status (Table III). We found higher risk of metastasis development in lymph node for combined T/A-A/A genotypes (OR = 2.53; 95% CI: 1.23–5.17). Additionally, the A allele genotype was significantly associated with HER2 positive tumour (OR = 2.53, 95% CI: 1.24–5.17). No significant correlation was noted between A allele genotype and age at diagnosis, tumour grade, size, and hormonal receptors status (ER and PR). However, the frequency of the FGF2 A allele was marginally higher in ductal than lobular carcinomas. The levels of FGF2 were analysed in 127 tumour sample and 76 serum samples of the subpopulation of BC patients (Table IV). Significantly higher FGF2 tumour levels were demonstrated in BC patients with the TA genotype of the –553 T/A polymorphism compared with those with the TT wild type genotype. No statistically significant difference in serum FGF2 levels was found between TT and TA genotypes (comparison was made for measurable levels of FGF2 (n = 23). We also determined whether the –553 T/A polymorphism of the FGF2 gene was associated with DFS and OS of BC patients. Survival analysis showed a significantly shorter DFS for carriers of the combined T/A-A/A genotypes when compared with carriers of the T/T genotype p = 0.0119 (Figure 1). No statistically significant association was found between polymorphic variants of the FGF2 gene and OS of BC patients, p = 0.2116 (Figure 2).


The -553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women.

Rykala J, Przybylowska K, Majsterek I, Pasz-Walczak G, Sygut A, Dziki A, Kuna P - Arch Med Sci (2014)

Kaplan-Meier disease-free survival (DFS) curves for breast cancer patients related to genotypes of –553 T/A FGF2 gene polymorphism; p = 0.0119; HR: 0.4516 (95% CI: 0.2119–0.9624)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495138&req=5

Figure 0001: Kaplan-Meier disease-free survival (DFS) curves for breast cancer patients related to genotypes of –553 T/A FGF2 gene polymorphism; p = 0.0119; HR: 0.4516 (95% CI: 0.2119–0.9624)
Mentions: We assessed whether the -553 T/A polymorphism was associated with various clinical parameters such as histological grade, tumour size, lymph node, ER, PR and HER2 status (Table III). We found higher risk of metastasis development in lymph node for combined T/A-A/A genotypes (OR = 2.53; 95% CI: 1.23–5.17). Additionally, the A allele genotype was significantly associated with HER2 positive tumour (OR = 2.53, 95% CI: 1.24–5.17). No significant correlation was noted between A allele genotype and age at diagnosis, tumour grade, size, and hormonal receptors status (ER and PR). However, the frequency of the FGF2 A allele was marginally higher in ductal than lobular carcinomas. The levels of FGF2 were analysed in 127 tumour sample and 76 serum samples of the subpopulation of BC patients (Table IV). Significantly higher FGF2 tumour levels were demonstrated in BC patients with the TA genotype of the –553 T/A polymorphism compared with those with the TT wild type genotype. No statistically significant difference in serum FGF2 levels was found between TT and TA genotypes (comparison was made for measurable levels of FGF2 (n = 23). We also determined whether the –553 T/A polymorphism of the FGF2 gene was associated with DFS and OS of BC patients. Survival analysis showed a significantly shorter DFS for carriers of the combined T/A-A/A genotypes when compared with carriers of the T/T genotype p = 0.0119 (Figure 1). No statistically significant association was found between polymorphic variants of the FGF2 gene and OS of BC patients, p = 0.2116 (Figure 2).

Bottom Line: Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples.Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23-5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49-6.99) (p = 0.002).Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Barlicki Hospital, Medical University of Lodz, Poland.

ABSTRACT

Introduction: Fibroblast growth factor-2 (FGF2) is an important signalling molecule contributing to angiogenesis, tumour growth and progression and its expression is implicated in breast cancer (BC) development. We investigated whether -553 T/A FGF2 gene polymorphism is associated with the risk and progression of BC in Polish women.

Material and methods: The -553 T/A polymorphism was genotyped in 230 breast cancer patients and 245 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples.

Results: The T/A genotypes (OR = 2.12, 95% CI: 1.20-3.74) (p = 0.08) and the combined heterozygotes T/A and homozygote A/A (OR = 2.18, 95% CI: 1.24-3.83) (p = 0.006) had an increased risk of BC. The median FGF2 levels in the tumours of A allele carriers were significantly increased compared to T/T patients, whereas in serum FGF2 levels were hardly altered among different genotype carriers. Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23-5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49-6.99) (p = 0.002). Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients.

Conclusions: Our study shows for the first time that the -553 T/A FGF2 gene polymorphism may be associated with a risk of BC developing and progression in Polish women and may have prognostic value for the assessment of BC high-risk groups.

No MeSH data available.


Related in: MedlinePlus