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Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians

Tumor Biology volume 36, pages 4223–4234 (2015)Cite this article

Abstract

The aim of present study was to evaluate the relationship between vascular endothelial growth factor (VEGF) −2578C/A, −2549I/D, −460T/C and −7C/T and VEGFR1 −710C/T polymorphisms with risk to breast cancer in North Indians. A total of 204 sporadic breast cancer patients and 204 controls were recruited for this case-control study. Significantly increased frequency of II genotype of −2549I/D polymorphism was observed in patients as compared to control individuals (odds ratio (OR) = 2.76, 95 % confidence interval (CI), 1.55–4.92; p = 0.0005). VEGF −2578AA genotype (OR = 2.87; 95 % CI, 1.61–5.10; p = 0.0003) and A allele (OR = 1.65, 95 % CI, 1.25–2.18; p = 0.0004) were found to be associated with increased risk for breast cancer. Individuals carrying CC genotype (OR = 2.23, 95 % CI, 1.25–3.97) and C allele (OR = 1.42, 95 % CI, 1.07–1.87) of VEGF −460T/C polymorphism were at higher risk of breast cancer. There was no significant difference in genotype and allele distribution of VEGF −7C/T and VEGFR1 −710C/T polymorphisms between cases and control individuals (p > 0.05). Linkage disequilibrium analysis showed a strong linkage between VEGF −2549I/D and −2578C/A polymorphisms (Lewontin’s \( \overset{^{\prime }}{D} \) = 0.99; r 2 = 0.97), −2549I/D and −460T/C (\( \overset{^{\prime }}{D} \) = 0.94; r 2 = 0.84), and −2578C/A and −460T/C polymorphisms (\( \overset{^{\prime }}{D} \) = 0.93; r 2 = 0.83). In the present study, we concluded that VEGF −2549I/D, −2578C/A and −460T/C polymorphisms are associated with risk to breast cancer in Punjab, North India.

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Fig. 1

Abbreviations

VEGF :

Vascular endothelial growth factor

SNP:

Single-nucleotide polymorphism

UTR:

Untranslated region

HWE:

Hardy-Weinberg equilibrium

PCR:

Polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

ARMS:

Amplification refractory mutation system

OR:

Odds ratio

CI:

Confidence interval

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Acknowledgments

We would like to thank the patients and control individuals for taking part in this study. This study was supported by the DBT grant BT/PR 13252/GBD/27/236/2009 sanctioned to KG and VS. Research fellowship (No. 3/1/3/JRF-2012/HRD) to RK from ICMR is duly acknowledged. We are thankful to Dr. Geeta Sharma, Principal, Sri Guru Ram Das Institute of Medical Sciences and Research, Vallah, Amritsar, Punjab, for their help in providing access to patients and facilities for execution of research work.

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Affiliations

  1. Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, 143005, Punjab, India

    Ruhi Kapahi, Kamlesh Guleria & Vasudha Sambyal

  2. Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India

    Mridu Manjari

  3. Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India

    Meena Sudan

  4. Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India

    Manjit Singh Uppal & Neeti Rajan Singh

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  1. Ruhi Kapahi
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Kapahi, R., Guleria, K., Sambyal, V. et al. Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians. Tumor Biol. 36, 4223–4234 (2015). https://doi.org/10.1007/s13277-015-3059-1

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Keywords

  • Breast cancer
  • Polymorphism
  • VEGF
  • VEGFR1