title: Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium.
abstract: Association studies in large series of breast cancer patients can be used to identify single-nucleotide polymorphisms (SNP) contributing to breast cancer susceptibility. Previous studies have suggested associations between variants in TP53 (R72P) and MDM2 (SNP309) and cancer risk. Data from molecular studies suggest a functional interaction between these genes. We therefore investigated the effect of TP53 R72P and MDM2 SNP309 on breast cancer risk and age at onset of breast cancer in a pooled series of 5,191 cases and 3,834 controls from the Breast Cancer Association Consortium (BCAC). Breast cancer risk was not found to be associated with the combined variant alleles [odds ratio (OR), 1.00; 95% confidence interval (95% CI), 0.81-1.23]. Estimated ORs were 1.01 (95% CI, 0.93-1.09) per MDM2 SNP309 allele and 0.98 (95% CI, 0.91-1.04) for TP53 R72P. Although we did find evidence for a 4-year earlier age at onset for carriers of both variant alleles in one of the breast cancer patient series of the BCAC (the German series), we were not able to confirm this effect in the pooled analysis. Even so, carriers of both variant alleles did not have different risk estimates for bilateral or estrogen receptor-positive breast cancer. In conclusion, in this large collaborative study, we did not find an association of MDM2 SNP309 and TP53 R72P, separately or in interaction, with breast cancer. This suggests that any effect of these two variants would be very small and possibly confined to subgroups that were not assessed in our present study.
authors.affiliation: Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
authors.forename: Scarlett
authors.initials: S
authors.lastname: Reincke
authors.forename: Annegien
authors.initials: A
authors.lastname: Broeks
authors.forename: Linde M
authors.initials: LM
authors.lastname: Braaf
authors.forename: Frans B L
authors.initials: FB
authors.lastname: Hogervorst
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Nichola
authors.initials: N
authors.lastname: Johnson
authors.forename: Olivia
authors.initials: O
authors.lastname: Fletcher
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.forename: Johanna
authors.initials: J
authors.lastname: Tommiska
authors.forename: Carl
authors.initials: C
authors.lastname: Blomqvist
authors.forename: Heli A
authors.initials: HA
authors.lastname: Nevanlinna
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Healey
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Van't Veer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D011960:Receptors, Estrogen; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2