To gain support for a causal role of these two ERE-associated SNPs (rs2839494 and rs1078272) in 21q22.3, we attempted to clarify alternative possibilities, including that (1) rs2839494 and rs1078272 might be in LD with an exon change in TMPRSS3 that affects protein function, (2) other changes in this 21q22.3 block might be within regulatory sequences and affect the level of expression through transcriptional regulation and (3) alterations in other adjacent genes might increase susceptibility to breast cancer progression. Here, TMPRSS3 is linked to breast carcinoma.