Polymorphisms and haplotype structures in genes for transforming growth factor β1 and its receptors in familial and unselected breast cancers

Jin, Qianren; Hemminki, Kari; Grzybowska, Ewa; Klaes, Ruediger; Söderberg, Magnus; Zientek, Helena; Rogozińska-Szczepka, Jadwiga; Utracka-Hutka, Beata; Pamuła, Jolanta; Pękala, Wioletta; Försti, Asta

doi:10.1002/ijc.20370

Cited by 86 publications

(86 citation statements)

References 31 publications

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“…Additionally, previous studies indicated that the TGFBR2 G-875A variant was not associated with breast cancer risk in the European population (21). However, results of the present study have shown that the -875A allele was marginally associated with a decreased risk of breast cancer.…”

Section: Discussioncontrasting

confidence: 78%

A functional polymorphism of TGFBR2 is associated with risk of breast cancer with ER+, PR+, ER+PR+ and HER2− expression in women

Zhang¹,

Guo²,

Cheng³

et al. 2011

Oncology Letters

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Abstract.Little is known about the correlation between TGFBR2 G-875A and breast cancer risk. Moreover, the associations of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) in breast cancer tissues with the TGFB1 C-509T, T+29C and TGFBR2 G-875A polymorphisms remain to be determined. In this study, we genotyped for TGFB1 C-509T, T+29C and TGFBR2 G-875A in fresh surgically resected tissues (n=82) and archived paraffin-embedded specimens (n=88) from 170 patients with breast cancer, as well as peripheral blood samples from 178 cancer-free female individuals. Evaluation of ER, PR and HER2 expression was performed using immunohistochemical staining. Logistic regression analysis was carried out to determine the risk of breast cancer by calculating the odds ratios (ORs) and their 95% confidence intervals (CIs). As a result, no difference was observed in the TGFB1 C-509T, T+29C genotype and allele frequencies between patients and controls. However, the frequency of the TGFBR2 -875A allele was marginally higher in cancer-free female individuals than that of women with breast cancer (24.2 vs. 17.9%, P=0.05). Notably, when stratification was performed by ER, PR and HER2 expression, the TGFBR2 -875A allele was found to correlate significantly to a decreased risk of breast cancer with ER + (OR=0.57, 95% CI 0.

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Section: Discussioncontrasting

confidence: 78%

A functional polymorphism of TGFBR2 is associated with risk of breast cancer with ER+, PR+, ER+PR+ and HER2− expression in women

Zhang¹,

Guo²,

Cheng³

et al. 2011

Oncology Letters

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“…Several genetic polymorphisms exist in the TGF-b1 gene, one of which is a T-C transition at nucleotide 29 of the coding region, resulting in a leucine to proline substitution at codon 10 (Blobe et al, 2000;Breast Cancer Association Consortium, 2006;Cox et al, 2007). This single nucleotide polymorphism (SNP) T29C, which is in strong linkage disequilibrium with another common SNP C-509T, has been studied extensively for its association with breast cancer risk and survival (Yokota et al, 2000;Goode et al, 2002;Hishida et al, 2003;Krippl et al, 2003;Ziv et al, 2003;Jin et al, 2004;Le Marchand et al, 2004;Shu et al, 2004;Kaklamani et al, 2005;Lee et al, 2005;Shin et al, 2005;Skerrett et al, 2005;Breast Cancer Association Consortium, 2006;Feigelson et al, 2006;Gonzalez-Zuloeta Ladd et al, 2007). Two studies found increased risk of breast cancer among Koreans and Dutch who carry the C allele (Lee et al, 2005;Gonzalez-Zuloeta Ladd et al, 2007), whereas two other studies showed decreased risk in relation to C genotype among Americans who were older than 65 years or Japanese who were premenopausal (Hishida et al, 2003;Ziv et al, 2003).…”

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confidence: 99%

TGF-β1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival

Katsaros

et al. 2008

Br J Cancer

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Transforming growth factor-b (TGF-b)-mediated signals play complicated roles in the development and progression of breast tumour. The purposes of this study were to analyse the genotype of TGF-b1 at T29C and TGF-b1 phenotype in breast tumours, and to evaluate their associations with IGFs and clinical characteristics of breast cancer. Fresh tumour samples were collected from 348 breast cancer patients. TGF-b1 genotype and phenotype were analysed with TaqMan s and ELISA, respectively. Members of the IGF family in tumour tissue were measured with ELISA. Cox proportional hazards regression analysis was performed to assess the association of TGF-b1 and disease outcomes. Patients with the T/T (29%) genotype at T29C had the highest TGF-b1, 707.9 pg mg À1 , followed by the T/C (49%), 657.8 pg mg À1 , and C/C (22%) genotypes, 640.8 pg mg À1 , (P ¼ 0.210, T/T vs C/C and C/T). TGF-b1 concentrations were positively correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival analysis showed TGF-b1 associated with disease progression, but the association differed by disease stage. For early-stage disease, patients with the T/T genotype or high TGF-b1 had shorter overall survival compared to those without T/T or with low TGF-b1; the hazard ratios (HR) were 3.54 (95% CI: 1.21 -10.40) for genotype and 2.54 (95% CI: 1.10 -5.89) for phenotype after adjusting for age, grade, histotype and receptor status. For late-stage disease, however, the association was different. The T/T genotype was associated with lower risk of disease recurrence (HR ¼ 0.13, 95% CI: 0.02 -1.00), whereas no association was found between TGF-b1 phenotype and survival outcomes. The study suggests a complex role of TGF-b1 in breast cancer progression, which supports the finding of in vitro studies that TGF-b1 has conflicting effects on tumour growth and metastasis.

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“…12 This promoter variant may alter TGFB1 transcription activity and the binding of the transcription factor Yin Yang 1. 18 Due to its functional relevance, several molecular epidemiological studies were performed to investigate the relationship between TGFB1 polymorphisms and risk of cancers, including breast-, 15,[19][20][21][22][23][24][25][26] prostate- 27,28 and hepatocellularcarcinoma. 16,17 However, to date no studies have focused on gastric cancer in Chinese population.…”

mentioning

confidence: 99%

Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population

Jin

Wang

Chen

et al. 2006

Intl Journal of Cancer

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Growing evidence suggests that the transforming growth factor b (TGF-b) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGFb1 and its receptor TGF-bRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C-509T and Leu10Pro polymorphisms in TGFB1 and G-875A variant in TGFBR2, using the primer-introduced restriction analysis (PIRA)-PCR assay, in a case-control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a significantly decreased risk of gastric cancer [adjusted odds ratio (OR) 5 0.65, 95% confidence interval (CI) 5 0.52-0.82 for 2509CT/TT and adjusted OR 5 0.67, 95% CI 5 0.53-0.85 for 2875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C-509T and TGFBR2 G-875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR 5 0.44, 95% CI 5 0.32-0.62). These findings indicate, for the first-time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility. ' 2006 Wiley-Liss, Inc.

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Polymorphisms and haplotype structures in genes for transforming growth factor β1 and its receptors in familial and unselected breast cancers

Cited by 86 publications

References 31 publications

A functional polymorphism of TGFBR2 is associated with risk of breast cancer with ER+, PR+, ER+PR+ and HER2− expression in women

A functional polymorphism of TGFBR2 is associated with risk of breast cancer with ER+, PR+, ER+PR+ and HER2− expression in women

TGF-β1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival

Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population

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