Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in Punjabi population from North West India

Abstract

The purpose of this study was to evaluate the association of seven VEGF promoter polymorphisms with breast cancer risk in Punjabi population from North West India. We screened DNA samples of 102 sporadic breast cancer patients and 102 unrelated healthy, gender, and age-matched individuals for seven VEGF promoter polymorphisms [-417 C/T (rs833062), -172 C/A (rs59260042), -165 C/T (rs79469752), -160 C/T, -152 G/A (rs13207351), -141 A/C (rs28357093) and -116 G/A (rs1570360)] by direct sequencing. The frequency of GG, GA, and AA genotype of -152 G/A polymorphism was 26.47 vs 38.34%, 46.08 vs 51.96%, and 27.45 vs 9.80%, in patients and controls, respectively. VEGF -152 AA genotype was significantly associated with increased risk for breast cancer (OR = 4.04, 95%CI, 1.69-9.68, p = 0.001; recessive model OR = 3.48, 95%CI, 1.59-7.63, p = 0.001). For VEGF -116 G/A polymorphism, G and A allele frequencies were 65.2 vs 76.47% and 34.8 vs 23.53% in patients and controls, respectively. Individuals having -116 AA genotype (OR = 3.40; 95%CI, 1.24-9.37; p = 0.014) and A allele (OR = 1.73; 95%CI, 1.12-2.67; p = 0.012) were associated with increased risk for breast cancer. VEGF -165 C/T and -141 A/C polymorphisms were associated with reduced risk for breast cancer. There was significantly decreased frequency of CT genotype (4.90 vs 18.63%; p = 0.002) and T allele (2.45 vs 9.31%; p = 0.003) of -165 C/T polymorphism among breast cancer patients as compared to controls. VEGF -141 A and C allele frequency were 96.57 vs 91.18% and 3.43 vs 8.82% in patients and controls, respectively. Significant reduced risk for breast cancer was observed with AC genotype (OR = 0.34, 95%CI, 0.14-0.86; p = 0.019) and C allele (OR = 0.37; 95%CI, 0.15-0.89; p = 0.023) of -141 A/C polymorphism. We did not observe association of VEGF -417 T/C, -172 C/A, -160 C/T polymorphisms with breast cancer risk in the studied subjects (p > 0.05). The VEGF -152 G/A and -116 G/A polymorphisms were found to be significantly associated with increased risk for breast cancer while -165 C/T and -141 A/C polymorphisms were found to be associated with decreased risk for breast cancer in Punjabi population from North West India.

Association between angiogenic growth factor genetic polymorphisms and the risk of osteosarcoma

“…Previous studies have reported that high expression levels of VEGF are found in several kinds of solid tumors, and correlate with the promotion of microvessel density in tumor tissues (Ferrara, 2002). Epidemiologic studies have investigated the role of VEGF gene polymorphisms in the susceptibility to solid tumors such as breast, lung, colorectal, gastric, and prostate cancers (Zhou et al, 2011;Maeda et al, 2013;Chen et al, 2014;Kapahi et al, 2014;Jannuzzi et al, 2015). Kapahi et al (2014) conducted a study to evaluate the association of seven VEGF gene polymorphisms with the risk of breast cancer, and they found that the VEGF -152G/A and -116G/A polymorphisms significantly increased the risk of breast cancer, and that the VEGF -165C/T and -141A/C gene polymorphisms were correlated with a decreased risk of cancer.…”

“…Epidemiologic studies have investigated the role of VEGF gene polymorphisms in the susceptibility to solid tumors such as breast, lung, colorectal, gastric, and prostate cancers (Zhou et al, 2011;Maeda et al, 2013;Chen et al, 2014;Kapahi et al, 2014;Jannuzzi et al, 2015). Kapahi et al (2014) conducted a study to evaluate the association of seven VEGF gene polymorphisms with the risk of breast cancer, and they found that the VEGF -152G/A and -116G/A polymorphisms significantly increased the risk of breast cancer, and that the VEGF -165C/T and -141A/C gene polymorphisms were correlated with a decreased risk of cancer. Maeda et al (2013) conducted a study in a Chinese population, and reported that the VEGF -460T/C polymorphism could influence tumor angiogenesis in nonsmall cell lung cancer.…”

“…Several single nucleotide polymorphisms (SNPs) in the 5'-and 3'-untranslated region have been reported to be associated with alteration of VEGF protein production, including -2578C/A, +936C/T, and -460T/C. Several previous studies have assessed the association between gene polymorphisms in VEGF and cancer risk, but the results have been inconsistent Kapahi et al, 2014;Yang et al, 2014;Rinck-Junior et al, 2015). However, only two studies have reported the association of VEGF gene variations with the risk of osteosarcoma (Tie et al, 2014;Wang et al, 2014).…”

Transcriptional regulation of the VEGF gene in dependence of individual genomic variations

“…For the SNPs À165 C/A (rs79469752), À152 A/G (rs13207351) and À141 A/C (rs28357093) only few epidemiological data are available. For À165 CT, À152 AA and À141 AC genotypes a differing risk was observed for North West Indian breast cancer patients [71].…”

Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer

“…22,21,12 VEGFA SNPs were shown to affect VEGFA levels in different cell models, 21,[23][24][25] including breast cancer. 26 VEGFA SNPs have also been associated with breast cancer susceptibility, 11,13,23,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] increased risk of progression 13,[40][41][42][43][44] or poor survival. 13,43 However, most of these works focused on the effects of SNPs evaluated separately, and the results from different authors present great disparity.…”