Common genetic variation in GATA-binding protein 3 and differential susceptibility to breast cancer by estrogen receptor α tumor status

Montserrat Garcia-Closas, Melissa A. Troester, Ying Qi, Anita Langerød, Meredith Yeager, Jolanta Lissowska, Louise Brinton, Robert Welch, Beata Peplonska, Daniela S. Gerhard, Inger Torhild Gram, Vessela Kristensen, Anne Lise Børresen-Dale, Stephen Chanock, Charles M. Perou

Research output: Contribution to journalArticlepeer-review


GATA-binding protein 3 (GATA3) is a transcription factor and a putative tumor suppressor that is highly expressed in normal breast luminal epithelium and estrogen receptor A (ER)-positive breast tumors. We hypothesized that common genetic variation in GATA3 could influence breast carcinogenesis. Four tag single-nucleotide polymorphisms (SNP) in GATA3 and its 3′ flanking gene FLJ4598 were genotyped in two case control studies in Norway and Poland (2,726 cases and 3,420 controls). Analyses of pooled data suggested a reduced risk of breast cancer associated with two intronic variants in GATA3 in linkage disequilibrium (rs3802604 in intron 3 and rs570613 in intron 4). Odds ratio (95% confidence interval) for rs570613 heterozygous and rare homozygous versus common homozygous were 0.85 (0.75-1.95) and 0.82 (0.62-0.96), respectively (Ptrend = 0.004). Stronger associations were observed for subjects with ER-negative, than ER-positive, tumors (Pheterogeneity = 0.01 for rs3802604; Pheterogeneity = 0.09 for rs570613). Although no individual SNPs were associated with ER-positive tumors, two haplotypes (GGTC in 2% of controls and AATT in 7% of controls) showed significant and consistent associations with increased risk for these tumors when compared with the common haplotype (GATT in 46% of controls): 1.71 (1.27-2.32) and 1.26 (1.03-1.54), respectively. In summary, data from two independent study populations showed two intronic variants in GATA3 associated with overall decreases in breast cancer risk and suggested heterogeneity of these associations by ER status. These differential associations are consistent with markedly different levels of GATA3 protein by ER status. Additional epidemiologic studies are needed to clarify these intriguing relationships.

Original languageEnglish (US)
Pages (from-to)2269-2275
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Issue number11
StatePublished - Nov 1 2007

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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