| 1. |
- Stevens, Kristen N, et al.
(författare)
-
19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
-
Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
|
|
| 2. |
- Fristrup, Niels, et al.
(författare)
-
Cathepsin E, Maspin, Plk1, and Survivin Are Promising Prognostic Protein Markers for Progression in Non-Muscle Invasive Bladder Cancer
- 2012
-
Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 180:5, s. 1824-1834
-
Tidskriftsartikel (refereegranskat)abstract
- Bladder cancer is a common cancer with particularly high recurrence after transurethral resection. In this study, we investigated the prognostic value of the protein expression of cathepsin E, maspin, polo-like kinase 1 (Plk1), and survivin in patients with stage Ta and T1 urothelial carcinomas. Transcripts from the four genes encoding these proteins were previously included in gene expression signatures for outcome prediction for Ta/T1 bladder cancer. We used three different tissue microarrays with 693 non-muscle invasive urothelial carcinomas from Danish, Swedish, and Spanish patient cohorts with long-term follow-up. Protein expression was measured by immunohistochemistry, and antibody specificity was validated by Western blotting. In the Danish patient cohort, we found the expression of cathepsin E, maspin, Plk1, and survivin to be significantly associated with progression to stage T2 to T4 bladder cancer (for each marker: log-rank test; P < 0.001). Multivariate Cox regression analysis identified cathepsin E (P < 0.001), Plk1 (P = 0.021), maspin (P = 0.001), and survivin (P = 0.001) as independent prognostic markers. Furthermore, maspin, survivin, and cathepsin E expression significantly subgrouped patients already stratified by European Organization for Research and Treatment of Cancer risk scores. Finally, we successfully validated the results in tumors from 410 patients from both Sweden and Spain. We conclude that all four protein markers may have prognostic value in non-muscle invasive bladder cancer for guiding optimal treatment of patients. Additional prospective studies are needed for further validation of the clinical relevance of this marker panel.
|
|
