MDM2 SNP309 is associated with high grade node positive breast tumours and is in linkage disequilibrium with a novel MDM2 intron 1 polymorphism.

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.

CA 19-9 and survival in advanced and unresectable pancreatic adenocarcinoma and cholangiocarcinoma.

BACKGROUND: The CA 19-9 tumour marker is increasingly used to monitor response to therapy in patients with pancreatic adenocarcinoma. Serum CA 19-9 levels have also been shown to correlate with survival. However, their role in cholangiocarcinoma is less clear. AIM OF STUDY: To assess the utility of CA 19-9 levels in the management of patients with advanced pancreatic adenocarcinoma or cholangiocarcinoma in routine clinical practice is the aim of the study. METHODS: A retrospective analysis of CA 19-9 values and survival was performed in 26 patients with pancreatic adenocarcinoma receiving gemcitabine and in 18 patients with cholangiocarcinoma. RESULTS: Patients with advanced pancreatic adenocarcinoma receiving gemcitabine who experienced a decrease of > or = 20% in CA 19-9 concentration had a median survival of 13.9+ months (range 4.2-23.5) compared to 7.6+ months (range 4.0-14.7) in those without such a change (p = 0.0109). In patients with advanced cholangiocarcinoma, the median survival was longest in those with a baseline CA 19-9 level of less than 1,000 U/ml; 11.8 months (range 1.0-41.4) vs 6.2 months (range 3.1-9.4; p = 0.0075). CONCLUSIONS: The CA 19-9 concentration has a valuable role in predicting outcome in patients with pancreatic adenocarcinoma and cholangiocarcinoma. It is helpful in guiding therapy and should be used accordingly in oncology practice.