The L10P Polymorphism and Serum Levels of Transforming Growth Factor β1 in Human Breast Cancer

Abstract

The L10P single nucleotide polymorphism (SNP) is located in the signal sequence of the transforming growth factor β1 (TGFβ1) 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 TGFβ1 variant observed in vitro and in male subjects. Here we investigated the association of the L10P SNP with serum levels of TGFβ1 in female breast cancer patients and controls. We genotyped the L10P SNP in 276 breast cancer patients and 255 controls. Serum TGFβ1 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 TGFβ to promote tumor progression. Mean TGFβ1 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 TGFβ1 levels of female Pro-allele carriers.

c.29C>T polymorphism in the transforming growth factor-β1 (TGFB1) gene correlates with increased risk of urinary bladder cancer

“…This polymorphism results in the replacement of leucine with proline at codon 10 of the amino acid sequence. As mentioned above, the 'Pro' allele has been shown to be a high activity allele in comparison to the 'Leu' allele [32]. Therefore, it appears that the higher activity c.29C>T alleles of TGFB1 increase the risk of bladder cancer significantly.…”

Association of the rs1346044 Polymorphism of the Werner Syndrome Gene RECQL2 with Increased Risk and Premature Onset of Breast Cancer

“…The study population has been described in detail in [ 36 , 37 ], and its clinical and histopathological characteristics are shown in Table 1 . 276 consecutive female breast cancer patients and 255 female controls (patients with benign gynecological lesions and healthy females) of European background were enrolled between 2002 and 2004 at the Department of Obstetrics and Gynecology, Medical University of Vienna (MUV), Austria.…”

TGF-β1 functional polymorphisms: a review

“…In an in vitro study, the allele c.+29C was shown to cause an increase in TGF-␤1 secretion compared with c.+29T [50]. Moreover, it was found that the serum concentration was higher in individuals with c.+29CC genotype than those with the c.+29CT or c.+29TT genotype [46,[52][53][54], and the serum concentration of TGF-␤1 was higher with the c.+74G allele in comparison with the c.+74C allele [54].…”