| 31. |
- Bartuma, Katarina, et al.
(author)
-
Genetic profiles distinguish different types of hereditary ovarian cancer.
- 2010
-
In: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 24:4, s. 885-895
-
Journal article (peer-reviewed)abstract
- Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles, with an average 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset. Discriminating genes within these regions include BRCA2, FOXO1A and RB1. Gains on chromosomes 17 and 19 characterized the HNPCC tumors, but target genes herein are unknown. The results indicate that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer.
|
|
| 32. |
- Begg, Colin B, et al.
(author)
-
Variation of breast cancer risk among BRCA1/2 carriers
- 2008
-
In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 299:2, s. 194-201
-
Journal article (peer-reviewed)abstract
- CONTEXT: The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers. OBJECTIVES: To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics. DESIGN, SETTING, AND PARTICIPANTS: Probands were identified from a population-based, case-control study (Women's Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years. MAIN OUTCOME MEASURE: Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families. RESULTS: Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics. CONCLUSION: There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.
|
|
| 33. |
|
|
| 34. |
- Bengtsson, Ylva, et al.
(author)
-
Serum copper, zinc and copper/zinc ratio in relation to survival after breast cancer diagnosis: A prospective multicenter cohort study
- 2023
-
In: Redox Biology. - 2213-2317. ; 63
-
Journal article (peer-reviewed)abstract
- BackgroundThe essential trace elements copper and zinc, and their ratio (copper/zinc), are important for maintaining redox homeostasis. Previous studies suggest that these elements may impact breast cancer survival. However, no epidemiological study has so far been conducted on the potential association between copper and copper/zinc levels and survival after breast cancer diagnosis. In this study, we aimed to examine the relationship between serum copper, zinc and copper/zinc levels and survival following breast cancer diagnosis.Patients and methodsThe Sweden Cancerome Analysis Network – Breast Initiative (SCAN-B) is a population-based cohort study including multiple participating hospitals in Sweden. A total of 1998 patients diagnosed with primary invasive breast cancer were followed for approximately nine years. Serum levels of copper and zinc and their ratio at the time of diagnosis was analyzed in relation to breast cancer survival using multivariate Cox regression, yielding hazard ratios (HR) with 95% confidence intervals.ResultsA higher copper/zinc ratio was associated with lower overall survival after breast cancer diagnosis. Comparing patients with a copper/zinc ratio in quartile 4 vs 1, the crude HR was 2.29 (1.65–3.19) (Ptrend ConclusionThere is evidence that the serum copper/zinc ratio provides an independent predictive value for overall survival following breast cancer diagnosis.
|
|
| 35. |
- Bergthorsson, J.T., et al.
(author)
-
BRCA1 and BRCA2 mutation status and cancer family history of Danish women affected with multifocal or bilateral breast cancer at a young age
- 2001
-
In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 38:6, s. 361-368
-
Journal article (peer-reviewed)abstract
- Introduction - A small fraction of breast cancer is the result of germline mutations in the BRCA1 and BRCA2 cancer susceptibility genes. Mutation carriers frequently have a positive family history of breast and ovarian cancer, are often diagnosed at a young age, and may have a higher incidence of double or multiple primary breast tumours than breast cancer patients in general. Objectives - To estimate the prevalence and spectrum of BRCA1 and BRCA2 mutations in young Danish patients affected with bilateral or multifocal breast cancer and to determine the relationship of mutation status to family history of cancer. Subjects - From the files of the Danish Breast Cancer Cooperative Group (DBCG), we selected 119 breast cancer patients diagnosed before the age of 46 years with either bilateral (n=59) or multifocal (n=61) disease. Methods - DNA from the subjects was screened for BRCA1 and BRCA2 mutations using single strand conformation analysis (SSCA) and the protein truncation test (PTT). Observed and expected cancer incidence in first degree relatives of the patients was estimated using data from the Danish Cancer Registry. Results - Twenty four mutation carriers were identified (20%), of whom 13 had a BRCA1 mutation and 11 carried a BRCA2 mutation. Two mutations in BRCA1 were found repeatedly in the material and accounted for seven of the 24 (29%) mutation carriers. The mutation frequency was about equal in patients with bilateral (22%) and multifocal breast cancer (18%). The incidence of breast and ovarian cancer was greatly increased in first degree relatives of BRCA1 and BRCA2 mutation carriers, but to a much lesser degree in relatives of non-carriers. An increased risk of cancer was also noted in brothers of non-carriers. Conclusions - A relatively broad spectrum of germline mutations was observed in BRCA1 and BRCA2 and most of the mutations are present in other populations. Our results indicate that a diagnosis of bilateral and multifocal breast cancer is predictive of BRCA1 and BRCA2 mutation status, particularly when combined with information on the patients' age at diagnosis and family history of breast/ovarian cancer.
|
|
| 36. |
- Bernstein, Jonine L., et al.
(author)
-
Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report
- 2013
-
In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 49:14, s. 2979-2985
-
Journal article (peer-reviewed)abstract
- Background: Women with germline BRCA1 or BRCA2 (BRCA1/BRCA2) mutations are at very high risk of developing breast cancer, including asynchronous contralateral breast cancer (CBC). BRCA1/BRCA2 genes help maintain genome stability and assist in DNA repair. We examined whether the risk of CBC associated with radiation treatment was higher among women with germline BRCA1/BRCA2 mutations than among non-carriers. Methods: A population-based, nested case-control study was conducted within a cohort of 52,536 survivors of unilateral breast cancer (UBC). Cases were 603 women with CBC and controls were 1199 women with UBC individually matched on age at diagnosis, race, year of first diagnosis and cancer registry. All women were tested for BRCA1 and BRCA2 mutations. Radiation absorbed dose from the initial radiotherapy (RT) to the CBC location within the contralateral breast was reconstructed from measurements in a tissue-equivalent phantom and details available in the therapy records. Findings: Among women treated with radiation, the mean radiation dose was 1.1 Gy (range = 0.02-6.2 Gy). Risk of developing CBC was elevated among women who carried a deleterious BRCA1/BRCA2 mutation (rate ratio, RR = 4.5, confidence interval, CI = 3.0-6.8), and also among those treated with RT (RR = 1.2, CI = 1.0-1.6). However, among mutation carriers, an incremental increase in risk associated with radiation dose was not statistically significant. Interpretation: Multiplicative interaction of RT with mutation status would be reflected by a larger association of RT with CBC among carriers than among non-carriers, but this was not apparent. Accordingly, there was no clear indication that carriers of deleterious BRCA/BRCA2 mutations were more susceptible to the carcinogenic effects of radiation than non-carriers. These findings are reassuring and have important clinical implications for treatment decisions and the clinical management of patients harbouring deleterious BRCA1/BRCA2 mutations. Funding: All work associated with this study was supported by the U.S. National Cancer Institute [R01CA097397, U01CA083178]. (C) 2013 Elsevier Ltd. All rights reserved.
|
|
| 37. |
- Bhandari, Vinayak, et al.
(author)
-
Divergent mutational processes distinguish hypoxic and normoxic tumours
- 2020
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
-
Journal article (peer-reviewed)abstract
- Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
|
|
| 38. |
- Bogdanska, Jasna, et al.
(author)
-
Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
- 2011
-
In: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 284:1-3, s. 54-62
-
Journal article (peer-reviewed)abstract
- The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1-5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of (35)S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.
|
|
| 39. |
|
|
| 40. |
- Bogdanska, Jasna, et al.
(author)
-
Tissue distribution of C-14-labelled perfluorooctanoic acid in adult mice after 1-5 days of dietary exposure to an experimental dose or a lower dose that resulted in blood levels similar to those detected in exposed humans
- 2020
-
In: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 239
-
Journal article (peer-reviewed)abstract
- Perfluorooctanoic acid (PFOA), a global environmental pollutant detected in both wildlife and human populations, has several pathophysiological effects in experimental animals, including hepatotoxicity, immunotoxicity, and developmental toxicity. However, details concerning the tissue distribution of PFOA, in particular at levels relevant to humans, are lacking, which limits our understanding of how humans, and other mammals, may be affected by this compound. Therefore, we characterized the tissue distribution of C-14-PFOA in mice in the same manner as we earlier examined its analogues perfluorooctanesulfonate (PFOS) and perfluorobutanesulfonate (PFBS) in order to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1, 3 or 5 days to a low dose (0.06 mg/kg/day) or a higher experimental dose (22 mg/kg/day) of C-14-PFOA, both scintillation counting and whole-body autoradiography revealed the presence of PFOA in most of the 19 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. There were no differences in the pattern of tissue distribution with the low and high dose and the tissue-to-blood ratios were similar. At both doses, PFOA levels were highest in the liver, followed by blood, lungs and kidneys. The body compartments estimated to contain the largest amounts of PFOA were the liver, blood, skin and muscle. In comparison with our identical studies on PFOS and PFBS, PFOA reached considerably higher tissue levels than PFBS, but lower than PFOS. Furthermore, the distribution of PFOA differed notably from that of PFOS, with lower tissue-to-blood ratios in the liver, lungs, kidneys and skin.
|
|
