Association of death receptor 4 haplotype 626C-683C with an increased breast cancer risk.
Dysregulation of apoptosis plays a crucial role in carcinogenesis. Tumour necrosis factor-related apoptosis-inducing ligand stimulates the extrinsic apoptotic pathway by binding to death receptor 4 (DR4). Thus, genetic alterations within the candidate tumour suppressor gene DR4 would be expected to provoke a deficient apoptotic signalling thereby facilitating the development of cancer. The DR4 variants Thr209Arg and Glu228Ala were genotyped in a series of 521 breast cancer cases and 1100 control subjects from Germany, determining their impact on breast cancer risk. Neither Thr209Arg (626C>G) nor Glu228Ala (683A>C) alone were significantly associated with breast cancer risk [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.65-1.08, P = 0.18 and OR = 0.89, 95% CI = 0.72-1.12, P = 0.30]. However, haplotype analysis revealed a 3.5-fold risk for carriers of the 626C-683C haplotype (OR = 3.52, 95% CI = 1.45-8.52, P = 0.003).
Frank
Bernd
B
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. b.frank@dkfz.de
Hemminki
Kari
K
Shanmugam
Kalai S
KS
Meindl
Alfons
A
Klaes
Rüdiger
R
Schmutzler
Rita K
RK
Wappenschmidt
Barbara
B
Untch
Michael
M
Bugert
Peter
P
Bartram
Claus R
CR
Burwinkel
Barbara
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human