The –553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women

Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoral breast cell lines. We identified putative regulatory elements, containing CCVs, that loop to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumor suppressor gene. Furthermore, the risk allele of CCV rs12155535, located in another DUSP4 enhancer element, was negatively correlated with looping of this element to the DUSP4 promoter region, suggesting that this allele would be associated with reduced expression. These findings provide the first evidence that CCV risk alleles downregulate DUSP4 expression, suggesting that this gene is a regulatory target of the 8p12 breast cancer risk locus.

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The association between TA-repeat polymorphism in the promoter region of UGT1A1 and breast cancer risk: a meta-analysis

Breast Cancer Research and Treatment ◽

10.1007/s10549-010-0742-1 ◽

2010 ◽

Vol 122 (3) ◽

pp. 879-882 ◽

Cited By ~ 15

Author(s):

Lei Yao ◽

Li-Xin Qiu ◽

Lu Yu ◽

Zhen Yang ◽

Xia-Jia Yu ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Promoter Region ◽

Meta Analysis ◽

Repeat Polymorphism

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A polymorphism in the promoter region of Ku70/XRCC6, associated with breast cancer risk and oestrogen exposure

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-009-0556-x ◽

2009 ◽

Vol 135 (9) ◽

pp. 1159-1168 ◽

Cited By ~ 25

Author(s):

Petra Willems ◽

Kim De Ruyck ◽

Rudy Van den Broecke ◽

Amin Makar ◽

Gianpaolo Perletti ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Promoter Region

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A meta-analysis on association of CYP2E1 rs2031920 and rs3813867 polymorphisms with breast cancer risk

Asia Pacific Journal of Molecular Biology and Biotechnology ◽

10.35118/apjmbb.2018.026.2.02 ◽

2018 ◽

pp. 9-16

Author(s):

Eric Tzyy Jiann Chong ◽

Lucky Poh Wah Goh ◽

Ping-Chin Lee

Keyword(s):

Breast Cancer ◽

Linkage Disequilibrium ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Promoter Region ◽

Literature Search ◽

Meta Analysis ◽

Cytochrome P450 2E1 ◽

Annual Increase ◽

Increase Rate

Breast cancer remains a challenging disease globally due to its heterogeneity and complexity, with an annual increase rate of 3.1%. Cytochrome P450 2E1 (CYP2E1) rs2031920 and rs3813867 polymorphisms that reside in the 5’-flanking promoter region of the gene are in a complete linkage disequilibrium and have been associated with breast cancer risk, but the findings are inconsistent and inconclusive. Therefore, we investigated the association of the CYP2E1 rs2031920 and rs3813867 polymorphisms with the risk of breast cancer through a meta-analysis. After literature search, eight eligible studies were included in this meta-analysis with a total of 3650 breast cancer cases and 3607 controls. Our meta-analysis revealed no significant association of the CYP2E1 rs2031920 and rs3813867 polymorphisms with breast cancer risk in all comparison models including the allelic (OR = 0.968, 95% CI = 0.855-1.097; p = 0.612), heterozygous (OR = 1.003, 95% CI = 0.869-1.159; p = 0.963), homozygous (OR = 0.792, 95% CI = 0.519-1.207; p = 0.278), dominant (OR = 0.987, 95% CI = 0.858-1.134; p = 0.851), and recessive (OR = 1.265, 95% CI = 0.831-1.924; p = 0.273). In conclusion, this meta-analysis suggests that the CYP2E1 rs2031920 and rs3813867 polymorphisms are not associated with the risk of breast cancer.

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Association of polymorphisms and haplotypes in the human growth hormone 1 (GH1) gene with breast cancer

Endocrine Related Cancer ◽

10.1677/erc.1.01073 ◽

2005 ◽

Vol 12 (4) ◽

pp. 917-928 ◽

Cited By ~ 13

Author(s):

K Wagner ◽

K Hemminki ◽

E Israelsson ◽

E Grzybowska ◽

R Klaes ◽

...

Keyword(s):

Breast Cancer ◽

Growth Hormone ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Promoter Region ◽

Human Growth ◽

Proximal Promoter ◽

Joint Analysis ◽

Nucleotide Polymorphisms ◽

Igf I

The growth hormone 1 (GH1)/insulin-like growth factor I (IGF-I) axis plays an important role in the development of breast cancer. By binding to its receptor, GH1 stimulates the production of IGF-I and its binding protein IGFBP3, resulting in the regulation of cell proliferation, differentiation and apoptosis. The GH1 gene expression is regulated by a highly polymorphic proximal promoter and a distal locus control region (LCR) 14.5 kb upstream of the gene. We investigated the effect of single nucleotide polymorphisms (SNPs) in the LCR and in the promoter region and an intron 4 SNP (IVS4+90 T/A) on breast cancer risk in a large cohort of Polish and German familial breast cancer cases and controls. SNPs in the LCR did not show an influence on breast cancer risk, either alone or in haplotypes. Three SNPs in the promoter region (G-340T, A-68G/C and A-63T/C) showed an increased and four SNPs (A-137G, G-119T, G-93delG and T-4G) a decreased allele frequency in the cases compared with the controls. Two of the SNPs (A-137G and G-93delG) lead to a decreased breast cancer risk among the minor allele carriers in the joint analysis of the two populations (odds ratio (OR) 0.62, 95% confidence interval (95% CI) 0.44–0.89, P=0.01 and OR 0.65, 95% CI 0.47–0.90, P=0.01, respectively). Haplotype analysis with these seven promoter SNPs revealed a protective association (OR 0.61, 95% CI 0.37–1.00, P=0.04) for the haplotype GAGdAAT, containing the G-93delG variant allele, which in the single analysis already showed a protective effect. The effect was marginally stronger in combination with the LCR GC haplotype (OR 0.49, 95% CI 0.23–1.01, P=0.04).

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Candidate Causal Variants at the 8p12 Breast Cancer Risk Locus Regulate DUSP4

Cancers ◽

10.3390/cancers12010170 ◽

2020 ◽

Vol 12 (1) ◽

pp. 170

Author(s):

Dylan M. Glubb ◽

Wei Shi ◽

Jonathan Beesley ◽

Laura Fachal ◽

Jayne-Louise Pritchard ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Promoter Region ◽

Risk Allele ◽

Regulatory Elements ◽

Genome Wide Association Studies ◽

Enhancer Element ◽

Causal Variants ◽

Risk Locus

Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoural breast cell lines. We identified putative regulatory elements, containing CCVs, which looped to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumour suppressor gene. Furthermore, the risk allele of CCV rs12155535, located in another DUSP4 enhancer element, was negatively correlated with looping of this element to the DUSP4 promoter region, suggesting that this allele would be associated with reduced expression. These findings provide the first evidence that CCV risk alleles downregulate DUSP4 expression, suggesting that this gene is a regulatory target of the 8p12 breast cancer risk locus.

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