Association Between the T29→C Polymorphism in the Transforming Growth Factor β1 Gene and Breast Cancer Among Elderly White Women

Ziv, Elad; Cauley, Jane A.; Morin, Phillip A.; Saiz, Robert; Browner, Warren S.

doi:10.1001/jama.285.22.2859

Cited by 113 publications

(104 citation statements)

References 21 publications

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“…In contrast with previous results, [17][18][19][20][21]36 we did not find a significant difference in plasma levels of TGF-β1 depending on codon 10 genotype in either patients or donors. This lack of effect may be due to the fact that the subjects did not have a homogenous state of immune activation (donors were in a resting state and patients were under different conditions depending on the stage of disease, or recent chemotherapy).…”

Section: Ii-iv (%) Iii-iv (%)contrasting

confidence: 99%

“…While codon 25 SNP have been consistently associated with decreased plasma levels, 17,18 conflicting data have been published regarding the impact of codon 10 SNP on plasma levels of TGF-β1. [17][18][19][20][21][22] These polymorphisms have been associated with an increased incidence of breast and colorectal neoplasia 20,23 and worse outcome following solid organ transplantation 24 and sibling HSCT. 5,25,26 To date there is no published evidence on the possible role of these SNP in unrelated donor HSCT, or on plasma TGF-β1 levels and clinical outcomes following transplantation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Berro¹,

Mayor²,

Maldonado-Torres³

et al. 2009

Haematologica

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BackgroundMany genetic factors play major roles in the outcome of hematopoietic stem cell transplants from unrelated donors. Transforming growth factor β1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Design and MethodsWe investigated the impact of single nucleotide polymorphisms at codons 10 and 25 of TGFB1, the gene encoding for transforming growth factor β1, on outcomes in 427 myeloablative-conditioned transplanted patients. In addition, transforming growth factor β1 plasma levels were measured in 263 patients and 327 donors. ResultsPatients homozygous for the single nucleotide polymorphism at codon 10 had increased non-relapse mortality (at 3 years: 46.8% versus 29.4%, P=0.014) and reduced overall survival (at 5 years 29.3% versus 42.2%, P=0.013); the differences remained statistically significant in multivariate analysis. Donor genotype alone had no impact, although multiple single nucleotide polymorphisms within the pair were significantly associated with higher non-relapse mortality (at 3 years: 44% versus 29%, P=0.021) and decreased overall survival (at 5 years: 33.8% versus 41.9%, P=0.033). In the 10/10 HLA matched transplants (n=280), recipients of non-wild type grafts tended to have a higher incidence of acute graft-versus-host disease grades II-IV (P=0.052). In multivariate analysis, when analyzed with patients' genotype, the incidences of both overall and grades II-IV acute graft-versushost disease were increased (P=0.025 and P=0.009, respectively) in non-wild-type pairs. ConclusionsWe conclude that increasing numbers of single nucleotide polymorphisms in codon 10 of TGFB1 in patients and donors are associated with a worse outcome following hematopoietic stem cell transplantation from unrelated donors.Key words: stem cell transplantation, TGF-β1, polymorphisms, survival, graft-versus-host disease.Citation: Berro M, Mayor NP, Maldonado-Torres H, Cooke L, Kusminsky G, Marsh SGE, Madrigal JA, and Shaw BE. Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation. Haematologica. 2010; 95:276-283. doi:10.3324/haematol.2009 This is an open-access paper.Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

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Section: Ii-iv (%) Iii-iv (%)contrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Berro¹,

Mayor²,

Maldonado-Torres³

et al. 2009

Haematologica

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“…In a cohort study involving 3075 women aged 65 years or older, Ziv et al (12) reported that subjects with the C/C TGF-␤ 1 genotype had a 64% reduced risk of developing breast cancer as compared with women with the C/T or T/T genotype. Results from a recent report of three case-control series of 3987 cases and 3867 controls confirmed that the T/T genotype was related to an increased risk of invasive breast cancer, but that the magnitude of the risk was much smaller than in the earlier study (odds ratio, 1.21 for C/C versus T carrier; Ref.…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms in the TGF- β 1 Gene and Breast Cancer Survival

et al. 2004

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The effect of genetic polymorphisms in the TGF-␤1 gene at codon 10 (T؉29C), codon 25 (G؉74C), and the promoter region [C 3 T at ؊509 from the transcription site, (C-509T)] on breast cancer survival was evaluated among a cohort of 1111 patients. The median follow-up time for the cohort was 5.17 years after cancer diagnosis. No DNA sequence variation at codon 25 of the TGF-␤1 gene was found, whereas polymorphisms in C-509T and T؉29C were in strong linkage disequilibrium. Patients who carried the C allele of T؉29C polymorphism had a reduced 5-year disease-free survival rate (75.6% for T/C, and 78.2% for C/C) compared with the T/T genotype (85.1%; P, 0.04); the age-adjusted hazard ratio was 1.5 (95% confidence interval, 1.1-2.2). Adjustment for clinical prognostic factors slightly attenuated the association (hazard ratio, 1.4, 95% confidence interval, 1.0 -1.9). Our study suggests that genetic polymorphisms in the TGF-␤1 gene may play a role in breast cancer progression.

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“…Two of them were in the promoter region at positions G-800A and C-509T. Two were located within the signal peptide sequence in exon 1 at codon 10 (CTG3 CCG) and codon 25 (CGG3 CCG), resulting in changes in the amino acid sequences (Leu 10 3 Pro and Arg 25 3 Pro, respectively). The last one was Table III).…”

Section: Tgf-␤1mentioning

confidence: 99%

“…6 Several polymorphisms in the TGF-␤1 and its receptor genes have been reported. 9 -11 After functional considerations, we selected 5 polymorphisms in the TGF-␤1 gene (G-800A, C-509T, Leu 10 3 Pro, Arg 25 3 Pro and Thr 263 3 Ile), one polyalanine polymorphism in the TGF-␤RI gene (9A36A) and 2 polymorphisms in the TGF-␤RII gene (G-875A and A-364G) to carry out a case-control study. Our aim was to test whether the 8 selected polymorphisms on the TGF-␤ signaling pathway were associated with familial or unselected breast cancer.…”

mentioning

confidence: 99%

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

Jin

Hemminki

Grzybowska

et al. 2004

Intl Journal of Cancer

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Alterations in TGF-␤ signaling appear to be associated with an altered risk of developing cancer, including breast cancer. We carried out a case-control study on 8 polymorphisms, including 5 in the TGF-␤1 gene (G-800A, C-509T, Leu 10 3 Pro, Arg 25 3 Pro and Thr 263 3 Ile), a polyalanine polymorphism (9A36A) in the TGF-␤RI gene and 2 (G-875A and A-364G) in the TGF-␤RII gene, using samples from 2 different populations, Polish familial and Finnish unselected breast cancer cases, together with ethnically and geographically matched controls. Additionally, familial breast cancer cases with respective controls from Sweden and Germany were studied in the Leu 10 3 Pro polymorphism, making the total number of familial cases 659. Allele, genotype and haplotype analysis on the TGF-␤1 gene as well as an analysis of the combinations of genotypes of the TGF-␤1 and its receptor genes in each individual were performed. Population differences in the allele and genotype distributions were found from 5 of the polymorphisms and 3 common haplotypes from the TGF-␤1 gene between the Finnish and other populations. However, no statistically significant difference between the breast cancer and healthy control groups was found for any of the 8 polymorphisms nor did the haplotype or genotype combination analysis reach statistical significance. Thus, none of the studied polymorphisms from the TGF-␤1 and its receptor genes was found to influence significantly susceptibility to breast cancer. The possible contribution of 6A/6A homozygosity in the TGF-␤RI gene to breast cancer needs to be confirmed in an independent study.

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Association Between the T29→C Polymorphism in the Transforming Growth Factor β1 Gene and Breast Cancer Among Elderly White Women

Abstract: Our findings suggest that TGF-beta1 genotype is associated with risk of breast cancer in white women aged 65 years or older. Because the T allele is the common variant and confers an increased risk, it may be associated with a large proportion of breast cancer cases.

Cited by 113 publications

References 21 publications

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Genetic Polymorphisms in the TGF- β 1 Gene and Breast Cancer Survival

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

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