| 1. |
- Eklund, Lena K., et al.
(författare)
-
Mutation analysis of the human homologue of drosophila patched and the xeroderma pigmentosum complementation group A genes in squamous cell carcinomas of the skin
- 1998
-
Ingår i: Molecular Carcinogenesis. - 0899-1987 .- 1098-2744. ; 21:2, s. 87-92
-
Tidskriftsartikel (refereegranskat)abstract
- The human homologue of Drosophila patched (PTCH), located at chromosome 9q22.3, was recently identified as a candidate tumor suppressor gene for familial and sporadic basal cell carcinomas. Squamous cell carcinomas (SCCs) of the skin display allelic loss in this chromosomal region, which, in addition to the PTCH gene, contains the DNA repair gene xeroderma pigmentosum complementation group A (XPA). Patients with xeroderma pigmentosum are predisposed to non-melanoma skin tumors because of deficient excision repair of ultraviolet-induced DNA damage. Mutation analysis by single-strand conformation analysis and direct DNA sequencing of all 23 exons of the PTCH gene and all six exons of the XPA gene in 14 SCCs did not reveal structural alterations in any of these genes. Additionally, analysis of PTCH expression by in situ hybridization in SCCs revealed no evidence of upregulation of PTCH mRNA, confirming the lack of mutations in this gene. These findings suggest that another, yet to be identified gene or genes on chromosome 9q are involved in SCC tumorigenesis.
|
|
| 2. |
|
|
| 3. |
- Gentile, Massimiliano, et al.
(författare)
-
p53 and survival in early onset breast cancer : analysis of gene mutations, loss of heterozygosity and protein accumulation
- 1999
-
Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 35:8, s. 1202-1207
-
Tidskriftsartikel (refereegranskat)abstract
- The p53 protein has proven to be central in tumorigenesis by its cell cycle regulatory properties and both gene mutations and protein accumulation have been associated with poor prognosis in breast cancer. The present study was undertaken to investigate the prognostic significance of gene mutations, p53 protein accumulation and of loss of heterozygosity (LOH) at the TP53 locus in young (age <37 years) breast cancer patients. In total, gene mutations were found in 21 of the 123 patients (17%), LOH in 20 of the 47 informative cases (43%) and protein accumulation in 47 of the 102 available cases (46%). Log rank analysis revealed no significant association between survival and TP53 mutations (in general), p53 protein accumulation or LOH. However, missense mutations localised to the zinc binding domain were significantly (P=0.0007) associated with poorer prognosis. As indicated in this as well as other studies, p53 protein accumulation is frequently found in young breast cancer patients, but this protein overexpression appears to be of minor significance for survival. Nevertheless, the present report also suggests that specific mutations contribute substantially to tumour aggressiveness.
|
|
| 4. |
- Lundin, Anna-Carin, et al.
(författare)
-
Association of breast cancer progression with a vitamin D receptor gene polymorphism
- 1999
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 59:10, s. 2332-2334
-
Tidskriftsartikel (refereegranskat)abstract
- The vitamin D3 receptor gene (VDR) contains a TaqI RFLP that is associated with increased VDR mRNA stability, increased serum levels of 1α,25-dihydroxyvitamin D3 (1,25-D3), and decreased risk for prostate cancer. Determination of the TaqI genotype, in a group of young women with breast cancer (n = 111; age, <37 years) and a control population (n = 130), revealed no overall association to risk for breast cancer. However, patients without TaqI site (TT genotype) showed a significantly increased risk for lymph node metastasis (relative risk, 1.8, 95% confidence interval, 1.3- 2.6). Furthermore, a tendency toward an increased survival was found among estrogen receptor-positive, tamoxifen-treated patients who were homozygous for the TaqI site (P = 0.075). We conclude that polymorphism in the VDR gene may influence tumor progression and tamoxifen treatment response in early- onset breast carcinomas.
|
|
| 5. |
- Söderkvist, Peter, et al.
(författare)
-
Glutathione S-transferase M1 null genotype as a risk modifier for solvent-induced chronic toxic encephalopathy
- 1996
-
Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 22:5, s. 360-363
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Exposure to organic solvents increases the risk of neuropsychiatric disability or chronic toxic encephalopathy (CTE). Polymorphisms in the biotransformation of xenobiotics and solvents may influence individual susceptibility to develop toxic effects. In this study the problem of whether there could be any association between the glutathione S-transferase M1 (GSTM1) null genotype and the risk for CTE, with regard to solvent exposure, was investigated.Methods Sixty patients referred to a clinic because of some degree of some degrees of psychiatric or neurological symptoms, as well as exposure to solvents, were examined by means of a validated questionnaire and psychometric testing. The degree of exposure to solvents was assessed by a thorough interview. According to clinical findings, the patients were classified into three categories as those with solvent-induced CTE, those with incipient CTE, and those who were non-CTE patients. Afterwards, leukocyte DNA (deoxyribonucleic acid) was isolated and the GSTM1 null genotype was determined by an assay based on polymerase chain reaction, blindly with regard to both exposure and disease status.Results The relative proportion (RP) of GSTM1 null genotypes was significantly increased for patients with a diagnosed CTE when they were compared with non-CTE patients (RP 2.55, 95% confidence interval 1.0--6.2). Dichotomizing the patients by high and low exposure revealed an increased risk for both GSTM1 gene carriers and the GSTM1 null genotype in the high-exposure group, the relative risks (RR) being 4.5 and 7.9, respectively. The chi-square for the Mantel extension for trend was 6.2 (P=0.025).Conclusion The GSTM1 null genotype acts as a risk modifier for CTE among patients occupationally exposed to solvents. The risk seems to increase in a dose-dependent fashion.
|
|
| 6. |
- Yngveson, A, et al.
(författare)
-
p53 Mutations in lung cancer associated with residential radon exposure.
- 1999
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- Unusual mutation patterns in lung tumors among underground miners have been indicated, suggesting radon-specific alterations in the genome, but the data are not consistent. To investigate the association between residential radon exposure and p53 mutations in lung tumors, we performed a study on cases from a nation-wide population-based investigation in Sweden. Our study included 83 nonsmoking lung cancer cases and 250 smoking lung cancer cases, diagnosed 1980-1984, with a time-weighted average radon exposure over 140 Bq/m3 or up to 50 Bq/m3. Radon was measured in dwellings occupied by the study subjects at some time since 1947. Information on smoking habits and other risk factors was obtained from questionnaires. After exclusions because of the initiation of treatment or insufficient material, the p53-status of 243 tumors was determined using PCR-single-stranded conformation polymorphism analysis and sequencing determination of exons 5-8. The overall mutation prevalence was 23.9%. An increased mutation prevalence was suggested among those with high exposure to residential radon [odds ratio (OR), 1.4; 95% CI, 0.7-2.6], especially among nonsmokers (OR, 3.2; 95% CI, 0.7-15.5), but no specific mutational pattern was indicated. Furthermore, the mutation prevalence seemed to be higher among smoking lung cancer cases than among nonsmoking cases (OR, 2.1; 95% CI, 0.9-5.0), and particularly among those smoking less than 10 cigarettes per day. It may be concluded that residential exposure to radon seems to contribute to a higher mutation prevalence of the p53 gene in lung tumors.
|
|
| 7. |
|
|
| 8. |
- Zhang, Hong, et al.
(författare)
-
K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa.
- 1998
-
Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 34:13, s. 2053-2057
-
Tidskriftsartikel (refereegranskat)abstract
- The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas. K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69 (6%) of transitional mucosa samples, but not in the normal mucosa. Further, mutation rates were increased in younger patients (P = 0.001) and in mucinous carcinomas (50%) compared with well differentiated (17%), moderately differentiated (26%) or poorly differentiated (24%) tumours. Our findings indicate that mucinous carcinoma may represent a distinct genetic entity.
|
|
