Dataset Information

No evidence that GATA3 rs570613 SNP modifies breast cancer risk.

ABSTRACT: GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P (trend) = 0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [Garcia-Closas M et al. (2007) Cancer Epidemiol Biomarkers Prev 16:2269-2275]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (OR(per-allele) = 1.00, 95% CI 0.94-1.05), in ER negative BCAC cases (OR(per-allele) = 1.02, 95% CI 0.91-1.13), in BRCA1 mutation carriers RR(per-allele) = 0.99, 95% CI 0.90-1.09) or BRCA2 mutation carriers (RR(per-allele) = 0.93, 95% CI 0.80-1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.

SUBMITTER: Johnatty SE

PROVIDER: S-EPMC2728174 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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No evidence that GATA3 rs570613 SNP modifies breast cancer risk.

Johnatty Sharon E SE Couch Fergus J FJ Fredericksen Zachary Z Tarrell Robert R Spurdle Amanda B AB Beesley Jonathan J Chen Xiaoqing X Gschwantler-Kaulich Daphne D Singer Christian F CF Fuerhauser Christine C Fink-Retter Anneliese A Domchek Susan M SM Nathanson Katherine L KL Pankratz Vernon S VS Lindor Noralane M NM Godwin Andrew K AK Caligo Maria A MA Hopper John J Southey Melissa C MC Giles Graham G GG Justenhoven Christina C Brauch Hiltrud H Hamann Ute U Ko Yon-Dschun YD Heikkinen Tuomas T Aaltonen Kirsimari K Aittomäki Kristiina K Blomqvist Carl C Nevanlinna Heli H Hall Per P Czene Kamila K Liu Jianjun J Peock Susan S Cook Margaret M Platte Radka R Gareth Evans D D Lalloo Fiona F Eeles Rosalind R Pichert Gabriella G Eccles Diana D Davidson Rosemarie R Cole Trevor T Cook Jackie J Douglas Fiona F Chu Carol C Hodgson Shirley S Paterson Joan J Hogervorst Frans B L FB Rookus Matti A MA Seynaeve Caroline C Wijnen Juul J Vreeswijk Maaike M Ligtenberg Marjolijn M van der Luijt Rob B RB van Os Theo A M TA Gille Hans J P HJ Blok Marinus J MJ Issacs Claudine C Humphreys Manjeet K MK McGuffog Lesley L Healey Sue S Sinilnikova Olga O Antoniou Antonis C AC Easton Douglas F DF Chenevix-Trench Georgia G

Breast cancer research and treatment 20081211 2

GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P (trend) = 0.00 ...[more]

PMID: 19082709

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Project description:BackgroundBreast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2) are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs) are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination.MethodsIn an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR) principle.ResultsNone of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP) interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082)A]), cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val]), cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln]), and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val]) pathways.ConclusionThe importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their biological interactions through SNPs have not been described. The strategy used here has the potential to identify complex biological links among breast cancer genes and processes. This will provide novel biological information, which will ultimately improve breast cancer risk management.

Dataset Information

No evidence that GATA3 rs570613 SNP modifies breast cancer risk.

Publications

No evidence that GATA3 rs570613 SNP modifies breast cancer risk.

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