Association of VEGF haplotypes with breast cancer risk in North-West Indians

Vasudha Sambyal,Ruhi Kapahi,Kamlesh Guleria,Manjit Singh Uppal,Neeti Rajan Singh,Meena Sudan,Mridu Manjari

doi:10.1186/s12920-021-01060-4

Vasudha Sambyal, Ruhi Kapahi + Show 5 more

Open Access

https://doi.org/10.1186/s12920-021-01060-4

Copy DOI

Abstract

BackgroundAngiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. VEGF is one of the most important endothelial cell mitogen and has a critical role in normal physiological and tumor angiogenesis. The objective of this study was to investigate the potential association of haplotypes of six VEGF polymorphisms with breast cancer risk in North-West Indians.MethodsSamples of 250 breast cancer patients and 250 age and sex matched controls were genotyped for VEGF −2578C/A, −2549I/D, −460T/C, +405C/G, −7C/T and +936C/T polymorphisms. Haplotypes were generated to determine the better contribution of VEGF polymorphisms to breast cancer risk.ResultsHaplotypes CDTCCC (OR = 0.56, 95%CI, 0.38–0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44–0.92; p = 0.018) of VEGF −2578C/A, −2549I/D, −460T/C, +405C/G, −7C/T and +936C/T polymorphisms were significantly associated with decreased risk of breast cancer. CDTCCC haplotype was also significantly associated with reduced risk of breast cancer in pre and post menopausal as well as both obese and non obese patients. Haplotype CDTGCC was marginally associated (p = 0.07) with reduced risk of breast cancer in non-obese patients as compared with non-obese controls where as haplotype AICGTC was marginally associated (p = 0.09) with reduced risk of breast cancer in obese patients when compared with non-obese patients. The CDTGCC haplotype was significantly associated with increased risk of breast cancer in premenopausal obese patients (OR = 1.98, 95%CI, 1.10–3.56; p = 0.02).ConclusionsOur data indicated that CDTCCC and CDTGCC haplotypes of VEGF −2578C/A, −2549I/D, −460T/C, +405C/G, −7C/T and +936C/T polymorphisms were significantly associated with breast cancer risk in North-West Indians. Further studies on multiethnic groups with larger sample size are required to confirm our results.

Highlights

Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer
We analyzed haplotypes of vascular endothelial growth factors (VEGF) −2578C/A, −2549I/D, −460T/C, +405C/G, −7C/T and +936C/T polymorphisms to determine if there is any difference in VEGF haplotypes between breast cancer patients and healthy controls
We observed that CDTCCC (OR = 0.56, 95%CI, 0.38–0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44–0.92; p = 0.018) haplotypes were significantly associated with decreased risk of breast cancer (Table 2)

Summary

Introduction

Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. Angiogenesis is one of the hallmark features of cancer [1] It is a complex and coordinated process regulated by different growth factors like platelet derived growth factor, transforming growth factor and angiopoietins among which vascular endothelial growth factors (VEGF) play a crucial role [2,3,4]. The VEGFA known as VEGF is located at 6p21.3 and it comprises eight exons and seven introns (Fig. 1) [13] It is highly polymorphic with several polymorphisms in the promoter, 5′-untranslated region (5′UTR) and 3′-UTR [14, 15]. Polymorphisms in promoter, 5′-UTR and 3′-UTR of VEGF have been reported to affect translation efficiency, circulating plasma concentrations and tumor tissue expression of VEGF [19, 27]. It has been documented that VEGF polymorphisms influencing VEGF expression in normal cells might have an impact on tumorigenesis, tumor progression, and response to anti-VEGF agents [22, 28,29,30]

Objectives

Methods

Results

Discussion

Conclusion