| 1. |
- Barrett, Jennifer H., et al.
(author)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Journal article (peer-reviewed)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 2. |
- Falck, Anna-Karin, et al.
(author)
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Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study
- 2012
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12
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Journal article (peer-reviewed)abstract
- Background: Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods: Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results: DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63-2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09-8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions: The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.
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| 3. |
- Hietala, Maria, et al.
(author)
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Natural remedy use in a prospective cohort of breast cancer patients in southern Sweden.
- 2011
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 50, s. 134-143
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Journal article (peer-reviewed)abstract
- Abstract Background. Complementary and alternative medicine (CAM) use is common among breast cancer patients. Several CAM therapies may have negative side effects or interact with conventional therapies. We studied biologically based CAM use with and without vitamins/minerals in relation to patient and tumor characteristics as well as treatment in an ongoing prospective cohort of 855 primary breast cancer patients. Methods. Patients from two hospitals in southern Sweden were included. Pre-operative and follow-up questionnaires containing questions on food intake, lifestyle, and concomitant medications, including natural remedies, were completed up to five years postoperatively. Clinical information was obtained from clinical records and tumor characteristics from pathology reports. Results. CAM and/or vitamins/minerals were used by 34.2% pre-operatively and by 57.9% during at least one visit. Over 100 different preparations were reported. At least eight of the commonly used preparations may interact with conventional breast cancer therapies. CAM users more often had a BMI <25 kg/m(2) (OR 1.76; 95%CI 1.33-2.33), were more often nulliparous (OR 1.59; 1.08-2.34), alcohol (OR 2.13; 1.44-3.14), antidepressants (OR 1.48; 1.02-2.15), and hormone therapy users (OR 1.57; 1.18-2.07), less often smokers (OR 0.71; 0.50-0.99), and consumed less coffee (OR 0.88; 0.82-0.95) than non CAM users. Tumor characteristics were not associated with CAM use. CAM use was more common among tamoxifen (OR 1.32; 1.00-1.75) and less common among chemotherapy (OR 0.63; 0.42-0.92) treated patients. Vitamins/minerals use was more common in aromatase inhibitor treated patients (OR 1.84; 1.33-2.53). There was no significant association between short-term disease-free survival and CAM use. Conclusion. CAM use was common and associated with certain patient characteristics. CAM use may cause clinically significant drug interactions and it is therefore of clinical interest to identify potential CAM users.
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