Transforming growth factor‐β1 genotype in sporadic breast cancer patients from India: status of enhancer, promoter, 5′‐untranslated‐region and exon‐1 polymorphisms

Abstract

Transforming growth factor beta (TGF-beta) is an example for a large and still-growing family of growth factors. TGF-beta1 is known to act both as a tumour suppressor and as a stimulator of tumour progression. This study examines the relationship amongst putative enhancer, promoter, 5'-untranslated-region (UTR) and exon-1 polymorphisms of the TGF-beta1 gene (region I from -1881 to -1613; region II from -1410 to -1123, and region III from -55 to +176, as per human genome organisation (HUGO) nomenclature) in 26 breast cancer patients and 97 healthy control subjects. The germline and somatic status of the four known polymorphisms was ascertained, and a significant difference was observed for the germline C/T and T/T genotype distribution between patients and controls in comparison to C/C genotypes at position -1349 (chi2 = 6.193; P = 0.009). In addition to the somatic variations observed for some of the regions studied, in 10/26 (38%) sporadic breast cancer cases, a novel somatic mutation in codon 47 of exon 1 (GenBank accession number AY059373) was also detected in tumour samples. The risk of cancer was found to be significant (OR = 4.525) for the -1349 C/T and T/T genotype background, suggesting that this genetic background may act as a risk factor for sporadic breast cancer.

Allelic diversity in the TGFB1 regulatory region: characterization of novel functional single nucleotide polymorphisms

“…Mouse and rabbit antisera were used as controls levels and increased risk of TGF-b1-related diseases in AAs remains to be determined. It should be noted that we expect allele p014, which was only found in AAs in our study, is also likely present in Caucasians since SNPs c.74G>C and c.-768_769insC are reported in other ethnicities including Caucasians (Awad et al 1998;Saha et al 2004).…”

“…Since SNPs can affect TGF-b1 expression, numerous studies have examined the association between SNPs and disease. For example, the c.-1347C>T SNP is associated with increased susceptibility and severity of asthma, risk of developing breast cancer and Alzheimer's disease (Luedecking et al 2000;Pulleyn et al 2001;Saha et al 2004;Silverman et al 2004). Additionally, the signal peptide SNPs have been associated with a gamut of diseases including carcinomas and pulmonary fibrosis (Arkwright et al 2000;Dunning et al 2003;Holweg et al 2001;Xaubet et al 2003).…”

No Association of the TGF-β1 29T/C Polymorphism with Breast Cancer Risk in Caucasian and Asian Populations: Evidence from a Meta-Analysis Involving 55, 841 Subjects

“…On the contrary many studies have reported no significant association between this SNP and breast cancer risk (Krippl et al, 2003;Jin et al, 2004;Saha et al, 2004;Cox et al, 2007b;Rajkumar et al, 2008).…”

“…A total of thirty-one research articles involving 24021 cases and 31820 controls were finally included in the present meta-analysis based on our selection (inclusionexclusion) criteria (Ziv et al, 2001;Dunning et al, 2003;Hishida et al, 2003;Krippl et al, 2003;Quarmby et al, 2003;Jin et al, 2004;Le Marchand et al, 2004;Saha et al, 2004;Shu et al, 2004;Kaklamani et al, 2005;Lee et al, 2005;Shin et al, 2005;Feigelson et al, 2006;Scola et al, 2006;Cox et al, 2007a;2007b;Gonullu et al, 2007;Rajkumar et al, 2008;Chen et al, 2011;Joshi et al, 2011;Pooja et al, 2013) (Figure 1). The major characteristics of selected studies are summarized in Table 1.…”

Polymorphisms of TGFβ1T+869C and C-509T with Lung Cancer Risk: A Meta-analysis

“…This transition was shown to be related to higher circulating levels of TGFβ1 [13,14]. Another polymorphism, a C-to-T substitution at nucleotide 506 (TGFβ1 C-509T, rs1800469), is associated with increased susceptibility and severity of asthma, risk of developing breast cancer and Alzheimer's disease [15][16][17]. This variant is located in the negative regulatory region, leading differential genetic regulation of TGFβ1 plasma levels [13].…”