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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 < 0.001). Association analysis with tumour pathology showed that low  TOX3  and  LOC643714  expression correlated with high Ki67 levels (p = 0.026 and p = 0.002) and the basal subtype (p < 0.001 and p < 0.001), whereas high expression correlated with ER (p = 0.004 and p < 0.001) and progesterone receptor (PgR) (p = 0.005 and p < 0.001) expression. Furthermore, high TOX3 and LOC643714 correlated with positive lymph nodes (p < 0.001 and p = 0.01). Patients with ER positive tumours and high levels of  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.

The risk allele of SNP rs3803662 and the mRNA level of its closest genes TOX3 and LOC643714predict adverse outcome for breast cancer patients