The L10P single nucleotide polymorphism (SNP) is located in the signal sequence of the transforming growth factor 1 (TGF1) gene. The proline-encoding (Pro-) allele of this SNP has been associated with an increased breast cancer risk, which has been attributed to the elevated secretion of this TGF1 variant observed in vitro and in male subjects. Here we investigated the association of the L10P SNP with serum levels of TGF1 in female breast cancer patients and controls. We genotyped the L10P SNP in 276 breast cancer patients and 255 controls. Serum TGF1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of the study population (n = 211). We found no evidence for an association of the L10P SNP with breast cancer risk (per-allele odds ratio: 0.91; 95% confidence interval: 0.71-1.16). However, patients with the Pro/Pro genotype exhibited a significantly younger age at breast cancer onset (55.2 +/- 14.3 years) than Leu/Leu patients (60.6 +/- 13.6 years; p = 0.04), which may reflect the ability of TGF to promote tumor progression. Mean TGF1 serum levels of Pro-allele carriers were 39.4 +/- 7.4 ng/mL, whereas those of Leu/Leu subjects were 37.6 +/- 6.0 ng/mL (p = 0.07). Thus, compared to a previous study of male subjects, we observed only a modest increase, if any, in TGF1 levels of female Pro-allele carriers.