Transforming growth factor beta 1 (TGFβ1) polymorphisms and haplotype structures have dual roles in breast cancer pathogenesis

Vitiello, Glauco Akelinghton Freire; Guembarovski, Roberta Losi; Hirata, Bruna Karina Banin; Amarante, Marla Karine; Oliveira, Carlos Eduardo Coral de; Oliveira, Karen Brajão de; Cebinelli, Guilherme Cesar Martelossi; Guembarovski, Alda Losi; Campos, Clodoaldo Zago; Watanabe, Maria Angélica Ehara

doi:10.1007/s00432-018-2585-9

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…Our results are reminiscent of a recent Brazilian study, which analyzed the positive association of 4-locus (rs1800468-rs1800469-rs1800470-rs1800471) CTCG TGFB1 haplotype with BC and with Her2+ status in the dominant model, but negative association of GCCG haplotype with BC but not BC-associated features. 12 This highlights the significance of haplotype analysis in disease-association studies, as suggested elsewhere. 47 Our study had several strengths.…”

Section: Discussionmentioning

confidence: 53%

“…The polymorphisms included in this study were the missense rs1800472 (+791C.T, T264I), rs1800471 (+74G.C, R25Q), and rs1800470 (+29T.C, P10L), and the 5# near-gene rs1800469 (-1347C.T) variants. 12,18,19,27,34 While MAF and genotype distribution of only rs1800471 was significantly different between BC cases and controls, the genotype distribution of rs1800469 homozygous variant was significantly higher in BC cases. The rs1800469 variant lies within a binding site for YY1 (Yin Yang 1), and the transition of C with T leads to reducing the ligation.…”

Section: Discussionmentioning

confidence: 91%

“…10,11 Paradoxically, TGFb1 has a dual role in cancer. 11,12 It was described to act as tumor suppressor in early carcinogenesis by inducing apoptosis or inhibiting cell growth, while promoting tumorigenicity and metastasis through suppression of local immunosurveillance and supporting tumor progression in advanced stages of cancer. 13,14 Located on chromosome 19 (19q13.1), TGFB1 gene contains several functional and non-functional polymorphisms, some of which were shown to contribute to altered BC susceptibility.…”

Section: Introductionmentioning

confidence: 99%

“…7,[15][16][17][18] Of these, rs1800469 (-1347C.T) promoter, rs1800470 (+29T.C) codon 10, and rs1800471 (+74G.C) signal peptide sequence variants were widely studied in BC. 15,[19][20][21][22] However, the association of TGFB1 variants with BC remains controversial, 12,15,17 and apparently varies in different ethnic groups. 12,23,24 No association 25,26 and weak/moderate association 25,27 were reported.…”

Section: Introductionmentioning

confidence: 99%

“…15,[19][20][21][22] However, the association of TGFB1 variants with BC remains controversial, 12,15,17 and apparently varies in different ethnic groups. 12,23,24 No association 25,26 and weak/moderate association 25,27 were reported. These apparently contradictory findings were explained by ethnicity-related variations, along with the likely interactions with related and distant variants.…”

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor beta 1 polymorphisms and haplotypes associated with breast cancer susceptibility: A case-control study in Tunisian women

et al. 2019

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Variable association of transforming growth factor beta 1 (TGFβ1) in breast cancer (BC) pathogenesis was documented, and the contribution of specific TGFB1 polymorphisms to the progression of BC and associated features remains poorly understood. We investigated the contribution of TGFB1 rs1800469, rs1800470, rs1800471, and rs1800472 variants and 4-locus TGFB1 haplotypes on BC susceptibility, and pathological presentation of BC subtypes. Study subjects comprised 430 female BC cases, and 498 cancer-free control women. BC-associated pathological parameters were also evaluated for correlation with TGFB1 variants. Results obtained showed that the minor allele frequency (MAF) of rs1800471 (+74G>C) was higher seen in BC cases than in control subjects, and was associated with increased risk of BC. Significant differences in rs1800471 and rs1800469 (−509C>T) genotype distribution were noted between BC cases and controls, which persisted after controlling for key covariates. TGFB1 rs1800472 was positively, while rs1800470 was negatively associated with triple negativity, while rs1800470 positively correlated with menarche, but negatively with tumor size and molecular type, and rs1800469 correlated positively with menstrual irregularity, distant metastasis, nodal status, and hormonotherapy. Heterogeneity in LD pattern was noted between the tested TGFB1 variants. Four-locus (rs1800472-rs1800471-rs1800470-rs1800469) Haploview analysis identified haplotype TGCT to be negatively associated, and haplotypes CGTT and CCCC to be positively associated with BC. This association of CGTT and CCCC, but not TGCT, with BC remained significant after controlling for key covariates. In conclusion, TGFB1 alleles and specific genotypes, and 4-locus TGFB1 haplotypes influence BC susceptibility, suggesting dual association imparted by specific SNP, consistent with dual role for TGFB1 in BC pathogenesis.

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Section: Discussionmentioning

confidence: 53%