Objective: We have identified a SNP within the seed-binding region for miR-502 in the 3'-UTR of the SET8 gene that codes for a methyltransferase for histone H4. SET8 methylates TP53 and thus regulates cell proliferation and genome stability. This study is to investigate the role for this SNP and its interaction with the TP53 codon 72 SNP in the age of onset of breast cancer.
Methods: We conducted a case-only study of 1, 110 breast cancer cases. PCR-RFLP was used for SNP genotyping. Ages of onset of breast cancer among different genotypes were analyzed using SAS software.
Results: Our analysis revealed that the SET8 CC and TP53 GG genotypes were independently associated with earlier age of onset of breast cancer in an allele-dose dependent manner. Moreover, individuals with both SET8 CC and p53 GG genotypes developed cancer at age of 47.74 years, compared with 54.55 years for individuals with both SET8 TT and TP53 CC genotypes.
Conclusions: miR-502-binding SNP in SET8 may modulate SET8 expression and contribute to early development of breast cancer either independently or together with the TP53 codon 72 SNP.