TY - JOUR
T1 - Death receptor 4 and bladder cancer risk
AU - Hazra, Aditi
AU - Chamberlain, Robert M.
AU - Grossman, H. Barton
AU - Zhu, Yong
AU - Spitz, Margaret R.
AU - Wu, Xifeng
PY - 2003/3/15
Y1 - 2003/3/15
N2 - Tumor necrosis factor-related apoptosis-inducing ligand stimulates the extrinsic apoptotic pathway by binding to death receptors 4 (DR4) and 5 (DR5). In DR4 exon 4, a C→G polymorphism at amino acid 626 located immediately 3′ to one of the main receptor ligand interface regions, results in a threonine→arginine change. We found that the DR4 exon 4 G/G genotype was associated with an overall decreased risk of bladder cancer in Caucasians [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.38-0.88]. This protective effect was more apparent in younger individuals (OR = 0.42; 95% CI, 0.20-0.87) than in older individuals (OR = 0.60; 95% CI, 0.35-1.02) and in women (OR = 0.45; 95% CI, 0.20-0.99) than in men (OR = 0.60; 95% CI, 0.36-0.99). Moreover, the protective effect was greater for light smokers (OR = 0.19; 95% CI, 0.06-0.59) compared with heavy smokers (OR = 0.83; 95% CI, 0.41-1.69). These data provide the first large-scale molecular epidemiological evidence that the DR4 polymorphism is associated with environmental exposure and bladder cancer risk, possibly through modulating the capacity of the receptor ligand complex to engage the apoptotic pathway.
AB - Tumor necrosis factor-related apoptosis-inducing ligand stimulates the extrinsic apoptotic pathway by binding to death receptors 4 (DR4) and 5 (DR5). In DR4 exon 4, a C→G polymorphism at amino acid 626 located immediately 3′ to one of the main receptor ligand interface regions, results in a threonine→arginine change. We found that the DR4 exon 4 G/G genotype was associated with an overall decreased risk of bladder cancer in Caucasians [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.38-0.88]. This protective effect was more apparent in younger individuals (OR = 0.42; 95% CI, 0.20-0.87) than in older individuals (OR = 0.60; 95% CI, 0.35-1.02) and in women (OR = 0.45; 95% CI, 0.20-0.99) than in men (OR = 0.60; 95% CI, 0.36-0.99). Moreover, the protective effect was greater for light smokers (OR = 0.19; 95% CI, 0.06-0.59) compared with heavy smokers (OR = 0.83; 95% CI, 0.41-1.69). These data provide the first large-scale molecular epidemiological evidence that the DR4 polymorphism is associated with environmental exposure and bladder cancer risk, possibly through modulating the capacity of the receptor ligand complex to engage the apoptotic pathway.
UR - http://www.scopus.com/inward/record.url?scp=0037444387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037444387&partnerID=8YFLogxK
M3 - Article
C2 - 12649168
AN - SCOPUS:0037444387
SN - 0008-5472
VL - 63
SP - 1157
EP - 1159
JO - Cancer Research
JF - Cancer Research
IS - 6
ER -