Abstract:
INTRODUCTION:A functional polymorphism within MDM2, SNP309 T>G, has been linked to early onset cancer. This study examined clinical associations of breast cancer with SNP309 in a Scottish Caucasian population and investigated additional MDM2 intron 1 polymorphisms. METHODS:Intron 1 of MDM2 was PCR amplified and directly sequenced from 299 breast cancer patients and 275 cancer free controls and compared with clinical and pathological parameters. RESULTS:SNP309 was observed, for the control and breast cancer cohorts respectively, at frequencies of: T/T = 44.7% and 39.5%; G/T = 42.2% and 47.2%; G/G = 13.1% and 13.4%, indicating that SNP309 is not a predisposing factor for breast cancer. The 309G/G genotype was associated with high grade tumours (OR = 1.64, 95%CI = 1.06-2.53, p = 0.025) and greater nodal involvement (OR = 2.51, 95%CI = 1.26-4.98, p = 0.009). SNP309 was not associated with an earlier age of cancer diagnosis. No association was observed between genotype and age of breast cancer diagnosis when patients were stratified by menopausal status and estrogen receptor status. Three additional low frequency SNPs were identified: 344T>A, 285G>C and 443G>T, the latter two novel. SNP285 was in complete linkage disequilibrium with SNP309 (D' = 1.0) with the minor alleles being in phase with each other. Moreover, the 285C/C, 309G/G double homozygous genotype was only observed in the breast cancer cohort. CONCLUSION:SNP309G/G is associated with poor prognostic breast cancer features in the Scottish population. Additionally, a novel SNP, SNP285, that is in linkage disequilibrium with SNP309, may also have a role in breast tumorigenesis.
journal_name
BMC Cancerjournal_title
BMC cancerauthors
Paulin FE,O'Neill M,McGregor G,Cassidy A,Ashfield A,Ali CW,Munro AJ,Baker L,Purdie CA,Lane DP,Thompson AMdoi
10.1186/1471-2407-8-281subject
Has Abstractpub_date
2008-10-01 00:00:00pages
281issn
1471-2407pii
1471-2407-8-281journal_volume
8pub_type
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