| 1. |
- Cederquist, Kristina, et al.
(författare)
-
A population based cohort study of patients with multiple colon and endometrial cancer: correlation of microsatellite instability (MSI) staus, age at diagnosis and cancer risk
- 2001
-
Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 91:4, s. 486-491
-
Tidskriftsartikel (refereegranskat)abstract
- Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant condition predisposing to cancers of primarily the colorectum and the endometrium. The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumours. Family histories of cancer were obtained on 89 persons with double primary (DP) cancers of the colon and the endometrium. The cancer risks in their 649 first-degree-relatives (FDR) were analysed. The microsatellite instability (MSI) status of the tumour of the proband was also analysed and the cancer risks were estimated in relation to MSI status and age at diagnosis in the proband (over or under 50 years). The overall standardised incidence ratio (SIR) was 1.69 (95% CI; 1.39-2.03). In the =50-year-old cohort the SIR was 2.67 (95% CI; 2.08-3.38). Colon, rectal and uterus cancer exhibited significantly increased risks. This risk was further increased in the =50-year-old MSI positive families. Several =50-year-old MSI negative HNPCC-like families with increased risks were also identified. In conclusion a FDR to a person with a DP cancer of the colorectum or the colon/endometrium have a significantly increased risk of having a colorectal or other HNPCC-associated cancers if the proband is diagnosed with one of the cancers before age 50. These families are candidates for genetic counselling and colorectal screening programmes. Mutations in mismatch repair genes can explain some of the increased risk in these families, but mutations in MSI negative families are probably due to other colon cancer susceptibility genes not yet described. Copyright 2001 Wiley-Liss, Inc.
|
|
| 2. |
- Cederquist, Kristina, et al.
(författare)
-
Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden
- 2004
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 109:3, s. 370-376
-
Tidskriftsartikel (refereegranskat)abstract
- Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder that predisposes to predominantly colorectal and endometrial cancers due to germline mutations in DNA mismatch repair genes, mainly MLH1, MSH2 and in families with excess endometrial cancer also MSH6. In this population-based study, we analysed the mutation spectrum of the MLH1, MSH2 and MSH6 genes in a cohort of patients with microsatellite unstable double primary tumours of the colorectum and the endometrium by PCR, DHPLC and sequencing. Fourteen of the 23 patients (61%) had sequence variants in MLH1, MSH2 or MSH6 that likely affect the protein function. A majority (10/14) of the mutations was found among probands diagnosed before age 50. Five of the mutations (36%) were located in MLH1, 3 (21%) in MSH2 and 6 (43%) in MSH6. MSH6 seem to have larger impact in our population than in other populations, due to a founder effect since all of the MSH6 families originate from the same geographical area. MSH6 mutation carriers have later age of onset of both colorectal cancer (62 vs. 51 years) and endometrial cancer (58 vs. 48 years) and a larger proportion of endometrial cancer than MLH1 or MSH2 mutation carriers. We can conclude that patients with microsatellite unstable double primary cancers of the colorectum and the endometrium have a very high risk of carrying a mutation not only in MLH1 or MSH2 but also in MSH6, especially if they get their first cancer diagnosis before the age of 50. Copyright 2004 Wiley-Liss, Inc.
|
|
| 3. |
|
|
| 4. |
- Hassler, Sven, et al.
(författare)
-
Fatal accidents and suicide among reindeer-herding Sami in Sweden
- 2004
-
Ingår i: International Journal of Circumpolar Health. - 1239-9736 .- 2242-3982. ; 63 Suppl 2, s. 384-388
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Over the last decades, reindeer-herding management has experienced drarnatic changes, e.g. increased motorization and socio-econornic pressure. The airn of the present study was to investigate whether these changes have increased the risk of fatal, work-related accidents and suicide between 1961 and 2000. Study design and methods. A c oh ort containing 7,482 members of reindeer-herding Sami families was extracted from national population registers. Information on fatal accidents and suicide was obtained from the Swedish Causes of Death Register, and compared to the expected number of deaths in a dernographica11y matched control population of non-Sami. Results. The ffiale reindeer her- ding Sami showed a significantly increased risk of dying from accidents such as vehicle accidents and poisoning. No significant increased risk of suicide was observed. A comparison between the periods of 1961-1980 and 1981- 2000 showed non-significant differences in risk, although a trend towards incre- ased risks was observed for most types of external causes of death except suicide. Conclusions. It is suggested that the increased socio-econornic pressure and the extensive use of terrain vehicles have increased the risk for fatal accidents arnong Swedish reindeer herders, and that commercial reindeer ma- nagement is one of the most dangerous occupations in Sweden
|
|
| 5. |
|
|
| 6. |
- Lindmark, Fredrik, et al.
(författare)
-
Analysis of the macrophage scavenger receptor 1 gene in Swedish hereditary and sporadic prostate cancer.
- 2004
-
Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 59:2, s. 132-140
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The macrophage scavenger receptor 1 (MSR1) gene on chromosome 8p22 was recently reported as a candidate gene for hereditary prostate cancer (HPC). Here, we further elucidate the role of MSR1 in both Swedish families with HPC and in a cohort of unselected prostate cancer. METHODS: DNA samples from 83 Swedish HPC families and 215 unselected population based cases of prostate cancer as well as 425 age-matched controls were genotyped. RESULTS: A total of 18 variants were identified, including 2 exonic, 7 intronic changes, and 9 changes in the 5'- or 3'-uncoding region. Of the two exonic changes, one previously reported truncation mutation was identified, a R293X nonsense mutation. This mutation was found in 2 of the 83 (2.4%) HPC families. The R293X mutation was found more frequently in men with PC (4.9%) than in unaffected men (2.7%), consistent with previous published results, however our results were not significant (P = 0.16). To additionally test for potential association of common sequence variants and increased risk for the disease, five common polymorphisms (PRO3, INDEL1, IVS5-57, P275A, INDEL7) were genotyped in the group of 215 prostate cancer cases and 425 age-matched controls. No association between any of the five common sequence variants and prostate cancer were found. CONCLUSION: Our results suggest that mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation. This study warrants further investigations of the role of MSR1 in prostate cancer etiology.
|
|
| 7. |
- Meuller, Johan, et al.
(författare)
-
Identification of genomic deletions of the APC gene in familial adenomatous polyposis by two independent quantitative techniques.
- 2004
-
Ingår i: Genetic testing. - : Mary Ann Liebert Inc. - 1090-6576 .- 1557-7473. ; 8:3, s. 248-56
-
Tidskriftsartikel (refereegranskat)abstract
- Large deletions in the APC (adenomatous polyposis coli) gene, causing familial adenomatous polyposis (FAP), cannot easily be detected by conventional mutation-detection techniques. Therefore, we have developed two independent quantitative methods for the detection of large deletions, encompassing one or more exons, of APC. Multiplex ligation-dependent probe amplification (MLPA) is performed in one reaction for the initial quantification of all APC exon copy numbers. Subsequently, quantitative real-time PCR (QRT-PCR) is used to verify the results obtained in the MLPA reaction. The identification of a deletion of the whole APC gene in a patient with classical FAP is described. The mutation was detected with the two quantitative methods and further verified on chromosomal level by the use of FISH (fluorescence in situ hybridization) on metaphase spreads. Furthermore, a large deletion covering exons 11-13 of the APC gene was detected in two apparently unrelated families. This deletion was further verified and characterized with long-range PCR. The MLPA test ensures a sensitive high-throughput screening for large deletions of the APC gene and can easily be implemented in the diagnostic testing for FAP.
|
|
| 8. |
|
|
| 9. |
- Wiklund, Fredrik, 1963-
(författare)
-
Genetic epidemiology of prostate cancer
- 2004
-
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.
|
|
