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| 2. |
- Beskow, Anna, et al.
(författare)
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Susceptibility locus for epidermodysplasia verruciformis not linked to cervical cancer in situ
- 2001
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Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661 .- 1601-5223. ; 135:1, s. 61-63
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Tidskriftsartikel (refereegranskat)abstract
- Cervical cancer is strongly associated with infection by oncogenic forms of human papillomavirus (HPV), mainly HPV 16 and HPV 18. The aim of this study was to test if a locus previously mapped to a region on chromosome 17 qter in patients with epidermodysplasia verucciformis (EV) and psoriasis and considered to be responsible for an increased susceptibility to HPV 5, also is linked to increased HPV susceptibility in cervical cancer in situ. We also wanted to test whether HPV 16 positivity cluster in families with cervical cancer. DNA was extracted from formalin fixed biopsies of 224 affected from 77 families diagnosed with cervical cancer in situ. Two microsatellite markers (D17S939 and D17S802) containing the locus were genotyped and linkage analysis was performed. No linkage was found to any of the two markers, neither when considering all cancer cases as affected nor when only considering HPV 16 infected cancer cases as affected in the analysis. We conclude that the susceptibility locus for HPV 5 infections associated with EV and psoriasis does not seem to affect susceptibility to HPV 16, frequently detected in cervical cancer. Also, positivity for HPV 16 did not show a significant clustering in families.
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| 3. |
- Björnsson, Jon Mar, et al.
(författare)
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Reduced proliferative capacity of hematopoietic stem cells deficient in hoxb3 and hoxb4
- 2003
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 23:11, s. 3872-3883
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Tidskriftsartikel (refereegranskat)abstract
- Several homeobox transcription factors, such as HOXB3 and HOXB4, have been implicated in regulation of hematopoiesis. In support of this, studies show that overexpression of HOXB4 strongly enhances hematopoietic stem cell regeneration. Here we find that mice deficient in both Hoxb3 and Hoxb4 have defects in endogenous hematopoiesis with reduced cellularity in hematopoietic organs and diminished number of hematopoietic progenitors without perturbing lineage commitment. Analysis of embryonic day 14.5 fetal livers revealed a significant reduction in the hematopoietic stem cell pool, suggesting that the reduction in cellularity observed postnatally is due to insufficient expansion during fetal development. Primitive Lin(-) Scal(+) c-kit(+) hematopoietic progenitors lacking Hoxb3 and Hoxb4 displayed impaired proliferative capacity in vitro. Similarly, in vivo repopulating studies of Hoxb3/Hoxb4-deficient hematopoietic cells resulted in lower repopulating capability compared to normal littermates. Since no defects in homing were observed, these results suggest a slower regeneration of mutant HSC. Furthermore, treatment with cytostatic drugs demonstrated slower cell cycle kinetics of hematopoietic stem cells deficient in Hoxb3 and Hoxb4, resulting in increased tolerance to antimitotic drugs. Collectively, these data suggest a direct physiological role of Hoxb4 and Hoxb3 in regulating stem cell regeneration and that these genes are required for maximal proliferative response.
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| 4. |
- Josefsson, Agnetha M., et al.
(författare)
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Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ : a nested case-control study
- 2000
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 355:9222, s. 2189-2193
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infection with certain types of human papillomavirus (HPV), which is common among young women, increases the risk of cervical cancer. However, less than 1% of young women positive for oncogenic types of HPV develop cervical cancer. We investigated whether the amount of HPV DNA is a useful predictor of progression to cervical carcinoma in situ. METHODS: We estimated the amount of HPV 16 DNA by a PCR that uses the 5'-exonuclease (Taqman) method, in 478 women with cervical carcinoma in situ and 608 individually matched controls. To adjust for differences in the amount of genomic DNA between samples, we estimated the amount of a nuclear gene (beta-actin). We studied multiple smears (total 3835 archived samples) from each woman, taken over periods of up to 26 years, that covered normal cytology to development of cervical cancer. FINDINGS: The risk of cervical carcinoma in situ increased with the amount of HPV 16 DNA. Analysis of the first smear from each woman, collected a mean of 7.8 years before cancer diagnosis, showed that women with the 20% highest amount of HPV 16 DNA were at a 60-fold higher risk of developing cervical carcinoma in situ than women negative for HPV 16. The first smear samples were classified as normal by squamous-cell cytology. INTERPRETATION: Analysis of the amount of HPV DNA can predict cancer risk at a stage when current screening methods are uninformative. Testing for the amount of HPV 16 DNA during gynaecological health checks might strikingly improve our ability to distinguish between infections that have a high or low risk of progressing into cervical cancer.
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| 5. |
- Magnusson, Patrik
(författare)
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Genetic susceptibility to cervical and gastric cancer
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cervical and gastric cancer both to a large extent depend on infectious agents. Cervical infection with human papilloma virus increases the risk for cervical cancer substantially, and infection with the bacteria Helicobacter pylori increases the risk for gastric cancer. Both types of infection are far more common than the types of cancer they are associated to, indicating that other factors are involved in the development of cervical and gastric cancer.The hypothesis of this thesis can be put as a question: Do inherited genetic variationmodify the risk for these forms of cancer, either independently of, or interactively with thepathogen? This hypothesis has been tested by genetic epidemiological studies on cervicalcancer, and by association studies on cervical as well as gastric cancer.Familial clustering is a prerequisite for involvement of inherited genetic factors to adisease. In this thesis evidence is presented for a significant familial clustering of cervicalcancer. This familial clustering was found to be restricted to biological relatives. No familialclustering was found for adoptive relatives. The pattern of familial clustering among firstdegree-, second degree-, and adoptive relations have been interpreted as evidence for geneticsusceptibility to cervical cancer. The heritability of cervical cancer was estimated to 27%.Possible stages of the disease development process during which inherited genotypes couldinfluence the risk of cervical cancer, are discussed.To test whether a candidate mutator-gene, hMLH1, is involved in the development ofcervical cancer, DNA from micro-dissected tumours was used for a loss of heterozygositystudy. Allelic loss of hMLH1 was not found to be necessary for cervical cancer development.DNA from epithelial or blood cells, harvested from cancer cases and controls, was usedin genetic association studies on cervical and gastric cancer. A previously reported genetic.association with cervical cancer is disputed, while significant associations between certain HLA alleles and gastric cancer are supported.
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| 6. |
- Ylitalo, Nathalie, et al.
(författare)
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A prospective study showing long-term infection with human papillomavirus 16 before the development of cervical carcinoma in situ
- 2000
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 60:21, s. 6027-6032
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus 16 (HPV16) is a predominant cause of cervical neoplasia. However, no population-based study with long-term follow-up has clarified the temporal relationship between HPV16 infection and occurrence of carcinoma in situ, or the importance of recurrent or persistent infection. This nested case-control study was carried out in a population-based cohort of women participating in cytological screening whose initial smear, taken in 1969-1995, was normal. During up to 26 years of follow-up, carcinoma in situ was diagnosed in 484 eligible women. Archival smears from these women were compared with smears from 619 individually matched controls. After DNA extraction, a highly sensitive PCR system was used to detect HPV16. Among case women, the prevalence of HPV16 positivity was 56% at the time of diagnosis. The relative risk of cervical carcinoma in situ increased from 3.6 (95% confidence interval, 1.2-11.0) 13 years before diagnosis to 11.1 (95% confidence interval, 5.5-22.2) 1 year before diagnosis. Having a positive smear at entry to the cohort increased risk >5-fold, whereas having persistent infection with HPV in two subsequent smears increased risk 30-fold. We estimated that among HPV16-positive women, the median incubation period from infection to carcinoma in situ was 7-12 years. We conclude that evidence of persistent and/or recurrent infection is associated with a drastically higher risk of cervical carcinoma in situ than occasional infection with HPV16.
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