TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis.
The transforming growth factor-beta (TGF-beta) 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-beta 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.
Castillejo
Adela
A
Grupo de Oncología Molecular, Hospital General Universitario de Elche, Elche, Spain.
Rothman
Nathaniel
N
Murta-Nascimento
Cristiane
C
Malats
Núria
N
García-Closas
Montserrat
M
Gómez-Martínez
Angeles
A
Lloreta
Josep
J
Tardón
Adonina
A
Serra
Consol
C
García-Closas
Reina
R
Chanock
Stephen
S
Silverman
Debra T
DT
Dosemeci
Mustafa
M
Kogevinas
Manolis
M
Carrato
Alfredo
A
Soto
José Luis
JL
Real
Francisco X
FX
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human