BMC Cancer (Dec 2012)

The risk allele of SNP rs3803662 and the mRNA level of its closest genes <it>TOX3</it> and <it>LOC643714</it> predict adverse outcome for breast cancer patients

  • Gudmundsdottir Eydis Th,
  • Barkardottir Rosa B,
  • Arason Adalgeir,
  • Gunnarsson Haukur,
  • Amundadottir Laufey Th,
  • Agnarsson Bjarni A,
  • Johannsson Oskar Th,
  • Reynisdottir Inga

DOI
https://doi.org/10.1186/1471-2407-12-621
Journal volume & issue
Vol. 12, no. 1
p. 621

Abstract

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Abstract Background The minor allele of SNP rs3803662 has been shown to correlate with increased breast cancer risk and with lower expression of TOX3. The SNP is closely located to TOX3 residing within an uncharacterised gene LOC643714. The aim of the study was to examine the association of the risk allele with expression of TOX3 and LOC643714, and of mRNA levels and genotype with clinical and pathological characteristics. Methods The SNP was genotyped in DNA isolated from blood and normal tissue from 160 breast cancer patients and mRNA levels were measured by microarrays and quantitative real-time (qRT)-PCR in breast tumours. Association with clinical and pathological characteristics was analysed by parametric tests. Results An association of the risk allele of rs3803662 with lower TOX3 expression was confirmed in oestrogen receptor (ER) positive tumours. It was more often observed in lobular tumours (p = 0.04), and carriers of the risk allele who had been diagnosed with luminal A tumours had shorter overall survival (OS) than carriers of the non-risk allele (p = 0.01). Positive correlation between the mRNA levels of TOX3 and LOC643714 was observed (r = 0.44 and p TOX3 and LOC643714 expression correlated with high Ki67 levels (p = 0.026 and p = 0.002) and the basal subtype (p TOX3 mRNA had shorter overall- and distant metastasis free-survival (p = 0.017 and p = 0.021), an effect mostly attributable to patients with luminal B tumours. Conclusions The results suggest that the effect of the risk allele of rs3803662 is strongest in luminal A tumours and that the expression levels of TOX3 and/or LOC643714 affect the progression of breast cancer. The effect may vary depending on the subtype and developmental stage of the tumour.

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