Background A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 (conditional p = 2.51 × 10−4; OR = 1.04; 95% CI 1.02–1.07) and rs77928427 (p = 1.86 × 10−4; OR = 1.04; 95% CI 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.

Recently, increased interletter spacing (LS) has been studied as a way to enhance reading fluency. It is suggested that increased LS improves reading performance, especially in poor readers. Theoretically, these findings are well substantiated as a result of diminished crowding effects. Empirically, however, findings on LS are inconclusive. In two experiments, we examined whether effects of increased LS are specific to children with dyslexia and whether increased LS affects word or sentence processing. In the first experiment, 30 children with dyslexia and 30 controls (mean age=9years 11months) read sentences in standard and increased LS conditions. In the second experiment, these sentences were read by an unselected sample of 189 readers (mean age=9years 3months) in either a sentence or word-by-word reading condition. The first experiment showed that increased LS affected children with dyslexia and controls in similar ways. Participants made fewer errors in the increased LS condition than in the standard LS condition. Reading rates were not affected. There were no indications that the effect of LS was related to reading ability, not even for a subgroup of readers. Findings of the second experiment were similar. Increased LS resulted in fewer errors, not faster reading rates. This was found only when complete sentences were presented, not when sentences were read word by word. Three main conclusions can be drawn. First, increased LS appears to affect reading accuracy only. Second, the findings do not support claims that increased LS specifically affects poor readers. And third, the effect of LS seems to occur at the interword level. Theoretical and practical implications of these findings are discussed.

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