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TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis

✍ Scribed by Adela Castillejo; Nathaniel Rothman; Cristiane Murta-Nascimento; Núria Malats; Montserrat García-Closas; Angeles Gómez-Martínez; Josep Lloreta; Adonina Tardón; Consol Serra; Reina García-Closas; Stephen Chanock; Debra T. Silverman; Mustafa Dosemeci; Manolis Kogevinas; Alfredo Carrato; José Luis Soto; Francisco X. Real

Publisher
John Wiley and Sons
Year
2009
Tongue
French
Weight
88 KB
Volume
124
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

The transforming growth factor‐beta (TGF‐β) signalling pathway plays an important role in tumor development and progression. We aimed at analyzing whether 7 different common variants in genes coding for 2 key members of the TGF‐β signalling pathway (TGFB1 and TGFBR1) are associated with bladder cancer risk and prognosis. A total of 1,157 cases with urothelial cell carcinoma of the bladder and 1,157 matched controls where genotyped for 3 single nucleotide polymorphisms (SNPs) in TGFB1 (rs1982073, rs1800472, rs1800471) and an additional 3 SNPs and 1 indel polymorphism in TGFBR1 (rs868, rs928180, rs334358 and rs11466445, respectively). In the case‐control study, we estimated odds ratios and 95% confidence intervals for each individual genetic variant using unconditional logistic regression adjusting for age, gender, study area and smoking status. Survival analysis was performed using the Kaplan‐Meier method and Cox models. The endpoints of interest were tumor relapse, progression and death from bladder cancer. All the SNPs analyzed showed a similar distribution among cases and controls. The distribution of the TGFBR1*6A allele (rs11466445) was also similar among cases and controls, indicating no association with bladder cancer risk. Similarly, none of the haplotypes was significantly associated with bladder cancer risk. Among patients with muscle‐invasive tumors, we found a significant association between __TGFBR1‐__rs868 and disease‐specific mortality with an allele dosage effect (p‐trend = 0.003). In conclusion, the genetic variants analyzed were not associated with an increased risk of bladder cancer. The association of __TGFBR1‐__rs868 with outcome should be validated in independent patient series. © 2008 Wiley‐Liss, Inc.

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