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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Schmidt MK,Reincke S,Broeks A,Braaf LM,Hogervorst FB,Tollenaar RA,Johnson N,Fletcher O,Peto J,Tommiska J,Blomqvist C,Nevanlinna HA,Healey CS,Dunning AM,Pharoah PD,Easton DF,Dörk T,Van't Veer LJ,Breast Cancer Associatidoi
10.1158/0008-5472.CAN-07-0738subject
Has Abstractpub_date
2007-10-01 00:00:00pages
9584-90issue
19eissn
0008-5472issn
1538-7445pii
67/19/9584journal_volume
67pub_type
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