Transforming growth factor-beta1 (TGFB1) is a multifunctional cytokine that may play an important role in the development and progression of cancer. The results of a number of association studies of TGFB1 polymorphisms and breast cancer risk are inconclusive. This study examined 4 single nucleotide polymorphisms (SNPs) in TGFB1 and risk of breast cancer using data previously collected from a population based case-control study (n=307 cases and 664 controls) of Caucasian women conducted in Northeastern Ontario, Canada. The SNPs (rs8179181, rs8110090, rs1800470 (L10P), rs1800469 (-509C/T)) were selected as either tag SNPs or had been identified as potentially functional in other studies, and were analysed using Taqman genotyping assays. Two of the SNPs were at the 5’ end (rs1800469 (-509C/T), rs1800470) and were in high LD (D’ 0.98); the remaining SNPs (rs8179181, rs8110090) were at the 3’ end and were also in high LD (D’ 0.99). In single-SNP analyses, the variant homozygous genotypes in rs1800470 (CC) and rs8179181 (AA) were significantly protective in the codominant model with Odds Ratios (OR) and 95% Confidence Intervals (95% CIs) of 0.63 (0.40-0.99) and 0.45 (0.21-0.96), while the AG genotype of rs8110090 was significantly associated with increased breast cancer risk with an OR of 1.78 (95% CI 1.14-2.77). Of the seven estimated haplotypes, 3 were significantly protective for breast cancer; when compared to the referent haplotype (see Table). In conclusion, our results suggest that SNPs at both the 3’ and 5’ end of TGFB1 may be associated with risk of breast cancer, and future studies examining additional polymorphisms in these regions would be valuable.

Haplotype association with breast cancer risk (n = 969; Global Haplotype Association p-value 0.0021)

rs8179181rs8110090rs1800470rs1800469FrequencyOR (95% CI)P-value
0.4028 1.00  
0.2387 0.73 (0.55–0.97) 0.03 
0.1728 0.67 (0.48–0.93) 0.017 
0.0671 0.49 (0.30–0.81) 0.0054 
0.056 0.55 (0.30–1.00) 0.052 
0.0298 1.00 (0.48–2.09) 0.99 
0.0227 1.82 (0.82–4.06) 0.14 
rs8179181rs8110090rs1800470rs1800469FrequencyOR (95% CI)P-value
0.4028 1.00  
0.2387 0.73 (0.55–0.97) 0.03 
0.1728 0.67 (0.48–0.93) 0.017 
0.0671 0.49 (0.30–0.81) 0.0054 
0.056 0.55 (0.30–1.00) 0.052 
0.0298 1.00 (0.48–2.09) 0.99 
0.0227 1.82 (0.82–4.06) 0.14 

Citation Format: Mary A. Bewick, Michael SC Conlon. A population-based study of Transforming Growth Factor-Beta1 (TGFB1) polymorphisms and risk of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1336. doi:10.1158/1538-7445.AM2013-1336