| 1. |
- Kainu, T, et al.
(författare)
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Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus
- 2000
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 97:17, s. 9603-9608
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Tidskriftsartikel (refereegranskat)abstract
- A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for breast cancer by using mathematical models to identify early somatic genetic deletions in tumor tissues followed by targeted linkage analysis. Comparative genomic hybridization was used to study 61 breast tumors from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations. Branching and phylogenetic tree models predicted that loss of 13q was one of the earliest genetic events in hereditary cancers. In a Swedish family with five breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared 13q21 germ-line haplotype in the family. Targeted linkage analysis was carried out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10). The multipoint logarithm of odds score under heterogeneity was 3.46. The results were further evaluated by simulation to assess the probability of obtaining significant evidence in favor of linkage by chance as well as to take into account the possible influence of the BRCA2 locus, located at a recombination fraction of 0.25 from the new locus. The simulation substantiated the evidence of linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative breast cancer predisposition locus in other populations.
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| 2. |
- Glimelius, Bengt, et al.
(författare)
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A systematic overview of radiation therapy effects in rectal cancer.
- 2003
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 42, s. 476-
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Tidskriftsartikel (refereegranskat)abstract
- A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for rectal cancer is based on data from 42 randomized trials and 3 meta-analyses. Moreover, data from 36 prospective studies, 7 retrospective studies and 17 other articles were used. A total of 131 scientific articles are included, involving 25 351 patients. The results were compared with those of a similar overview from 1996 including 15 042 patients. The conclusions reached can be summarized thus: The results after rectal cancer surgery have improved during the past decade. It is likely that local failure rates after 5 years of follow-up at hospitals adopting the TME-concept (TME = total mesorectal excision) have decreased from about 28% to 10-15%. Preoperative radiotherapy at biological effective doses above 30 Gy decreases the relative risk of a local failure by more than half (50-70%). Postoperative radiotherapy decreases the risk by 30-40% at doses that generally are higher than those used preoperatively. There is strong evidence that preoperative radiotherapy is more effective than postoperative. There is moderate evidence that preoperative radiotherapy significantly decreases the local failure rate (from 8% to 2% after 2 years) also with TME. There is strong evidence that preoperative radiotherapy improves survival (by about 10%). There is no evidence that postoperative radiotherapy improves survival. There is some indication that survival is prolonged when postoperative radiotherapy is combined with concomitant chemotherapy. Preoperative radiotherapy at adequate doses can be given with low acute toxicity. Higher, and unacceptable acute toxicity has been seen in some preoperative radiotherapy trials using suboptimal techniques. Postoperative radiotherapy can also be given with acceptable acute toxicity. The long-term consequences of radiotherapy appear to be limited with adequate radiation techniques, although they have been less extensively studied. Longer follow-up periods are needed before firm conclusions can be drawn. Peroperative radiotherapy, preferably preoperative since it is more effective, is routinely recommended for most patients with rectal cancer since it can substantially decrease the risk of a local failure and increases survival. In a primarily non-resectable tumour, preoperative radiotherapy can cause tumour regression allowing subsequent radical surgery. This therapy is routinely indicated. Whether radiochemotherapy is more efficient than radiotherapy alone is not clear, since the results of four small randomized trials are partly conflicting. Preoperative radiotherapy, frequently combined with chemotherapy, has been used to increase the chances of sphincter-preserving surgery in low-lying tumours. The literature is inconclusive with respect to how frequently this occurs. Radiotherapy frequently produces symptom relief in patients with rectal cancer not amendable to surgery.
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| 3. |
- Grönberg, Henrik, et al.
(författare)
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BRCA2 mutation in a family with hereditary prostate cancer
- 2001
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 30:3, s. 299-301
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary prostate cancer is a genetically heterogeneous disease, and so far four different susceptibility loci have been identified. Reports of associated cancers are few, and it is generally considered a sire-specific disease. However, some reports have shown an elevated risk for prostate cancer among BRCA2 mutation carriers. In this report, we present a family in which the father and four of his sons were diagnosed with prostate cancer at exceptionally early ages (51, 52, 56, 58, and 63 years, respectively). In addition, three daughters were diagnosed with breast cancer between the ages of 47 and 61. In this family, a truncating mutation in exon 11, 6051delA of the BRCA2 gene, leading to an early termination of the protein (codon 1962), was identified. Although BRCA2 is probably responsible only for a very small fraction of hereditary prostate cancers, this finding supports previous reports of an increased risk of prostate cancer in BRCA2 mutation carriers.
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| 4. |
- Nilbert, Mef, et al.
(författare)
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Viktigt att upptäcka ärftliga fall av kolorektal- och endometriecancer. Mutationer hos »HNPCC-individer» kan orsaka flera tumörsjukdomar
- 2002
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Ingår i: Läkartidningen. - 0023-7205. ; 99:34, s. 300-3296
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is one of our most common hereditary cancer syndromes and confers an increased risk for several tumor types, with the greatest lifetime risks being for colorectal cancer and endometrial cancer. Hereditary mutations in one of several mismatch-repair (MMR) genes cause the syndrome, and 39 such mutations, involving the genes MLH1, MSH2 and MSH6, have been been characterized in Sweden. Screening programs for HNPCC have been shown to be cost-effective and to prevent cancer. Identification of HNPCC individuals thus allows prevention of additional tumors in the patient as well as in the family.
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| 5. |
- Wiklund, Fredrik, 1963-
(författare)
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Genetic epidemiology of prostate cancer
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer is a major health burden throughout the world, yet the etiology of prostate cancer is poorly understood. Evidence has accumulated supporting the existence of a hereditary form of this disease. Improved understanding of the genetic mechanisms underlying the development and progression of prostate cancer would be a major advance for improved prevention, detection and treatment strategies. This thesis evaluates different aspects of the genetic epidemiology of prostate cancer. In a genomic scan two chromosomal regions with evidence for linkage was observed. The strongest support was found on chromosome 19p with an allele sharing LOD score of 2.91 (genome-wide P = 0.032). The second region, showing suggestive evidence of linkage, was observed in the centromeric region of chromosome 5. Linkage analyses of densely spaced markers on chromosome 8p22-23 confirmed (P = 0.03) previously reported linkage to this region. A systematic evaluation of the possible impact that the RNASEL gene have on prostate cancer was performed. Overall, limited evidence for association with prostate cancer risk was found. The results provide strong evidence against a role of RNASEL in prostate cancer etiology in Sweden. In a comprehensive evaluation of occurrence of other malignancies in HPC families, previously reported association between gastric and prostate carcinoma was confirmed. The increased risk was of the same magnitude in early and late onset HPC families and confined to only male relatives. A genome-wide linkage analysis, stratified by occurrence of gastric carcinoma, identified a novel susceptibility locus on chromosome Xp21. In summary, chromosome 5q and 19p represents the regions most likely to harbor susceptibility genes predisposing to prostate cancer in the Swedish population. A common genetic basis for both gastric and prostate cancer has been confirmed and a novel susceptibility locus on chromosome Xp21 has been identified.
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