Association of death receptor 4 haplotype 626C–683C with an increased breast cancer risk

• Published in: Carcinogenesis (New York) Vol. 26; no. 11; pp. 1975 - 1977
• Main Authors: Frank, Bernd, Hemminki, Kari, Shanmugam, Kalai S., Meindl, Alfons, Klaes, Rüdiger, Schmutzler, Rita K., Wappenschmidt, Barbara, Untch, Michael, Bugert, Peter, Bartram, Claus R., Burwinkel, Barbara
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2005; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Biological and medical sciences; Breast Neoplasms - genetics; Carcinogenesis, carcinogens and anticarcinogens; Case-Control Studies; death receptor 4; DR4; Female; Genetic Carrier Screening; Genetic Predisposition to Disease; Genotype; Gynecology. Andrology. Obstetrics; Haplotypes - genetics; Humans; Mammary gland diseases; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor - genetics; single nucleotide polymorphism; SNP; TNF; TNF-related apoptosis-inducing ligand; TRAIL; Tumors; tumour necrosis factor; Mammary gland diseases; Death receptor 4; Association; Risk factor; Breast cancer; Malignant tumor; Epidemiology; Haplotype
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgi164

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).