| 1. |
- Borg, Åke, et al.
(författare)
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Novel germline p16 mutation in familial malignant melanoma in southern Sweden
- 1996
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Ingår i: Cancer Research. - 0008-5472. ; 56:11, s. 500-2497
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Tidskriftsartikel (refereegranskat)abstract
- The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and M9). The mutation results in an insertion of Arg at codon 105, which interrupts the last of the four ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. All five tested individuals of Lund M2 and M9 affected by melanoma were mutation carriers, as were five melanoma-free individuals. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas and a non-Hodgkin's lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 revealed that both families share a common haplotype, in keeping with a common ancestor.
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| 2. |
- Brandt, L, et al.
(författare)
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Blood transfusion as a risk factor for non-Hodgkin lymphoma
- 1996
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Ingår i: British Journal of Cancer. - 0007-0920. ; 73:9, s. 1148-1151
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Tidskriftsartikel (refereegranskat)abstract
- In a case-control study of 280 out of 426 consecutive patients with a recent diagnosis of non-Hodgkin lymphoma (NHL) and 1827 control subjects, 53 (19%) and 230 (13%) respectively had received blood transfusions 1 year or more before the interview. Using an age- and sex-stratified analysis the odds ratio (OR) for transfusion was 1.74 (95% CI 1.24-2.44). ORs were also determined for transfusions received in the intervals 1-5, 6-15, 16-25 and > or = 26 years before diagnosis. In the interval 6-15 years, the OR for transfusion was 2.83 (95% CI 1.60-4.99) whereas ORs for transfusions received in other intervals were lower and not significantly elevated. Histological diagnoses (Kiel classification) and results of staging procedures were known for 185 patients. For low-grade NHL of nodal B-cell chronic lymphocytic leukaemia (B-CLL) or immunocytoma type, the OR for transfusions was 4.15 (95% CI 1.92-9.01). For low-grade nodal lymphomas of follicle centre cell type and high-grade nodal lymphomas, no relation to transfusions could be demonstrated. For high-grade extranodal lymphoma as sole manifestation, OR for transfusions was 3.27 (95% CI 1.30-8.24). It is concluded that blood transfusion may be a risk factor for NHLs especially those of B-CLL or immunocytoma type and for high-grade extranodal lymphoma.
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| 3. |
- Fernö, Mårten, et al.
(författare)
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Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay
- 1996
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 32a:5, s. 793-801
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Tidskriftsartikel (refereegranskat)abstract
- Urokinase plasminogen activator (uPA) is involved in the activation of different proteases which participate in the degradation of extracellular matrix, thereby enhancing the invasive capacity of tumour cells. uPA has been shown to be of prognostic importance in breast cancer. We have analysed uPA with a new luminometric immunoassay (LIA), applicable in cytosol samples routinely used for oestrogen-receptor (ER) and progesterone-receptor (PgR) analyses. At a cut-off value of 0.62 ng uPA/mg protein, 33% (230/688) samples were classified as representing high uPA tumours. High uPA content was found to be associated with shorter recurrence-free survival (median observation time: 42 months), ER and PgR negativity, increased p53 expression, DNA non-diploidy and a high S-phase fraction (SPF), but not with lymph node involvement or tumour size (< or = 20 mm versus > 20 mm). In the subgroup of patients not treated with systemic adjuvant therapy, multivariate analysis showed uPA to be an independent prognostic factor together with lymph node status and SPF. If these results can be reproduced, uPA may be a factor suitable for inclusion in a prognostic index.
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| 4. |
- Heimdal, K, et al.
(författare)
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Familial testicular cancer in Norway and southern Sweden
- 1996
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Ingår i: British Journal of Cancer. - 0007-0920. ; 73:7, s. 9-964
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Tidskriftsartikel (refereegranskat)abstract
- Information about occurrence of testicular cancer (TC) in relatives of TC patients has been collected using questionnaires from 797 out of 922 consecutive Norwegian and 178 out of 237 Swedish patients with TC seen at the Norwegian Radium Hospital and the University Hospital Lund in Sweden during 1981-91. Fifty-one Norwegian and five Swedish patients had a relative with confirmed TC. Thus, 51/922 (5.5%) of the Norwegian and 5/237 (2.1%) of the Swedish patients treated during the time interval investigated were considered to have familial TC. Thirty-two of the patients had an affected first-degree relative. Expected numbers of cancers in the relatives were computed from data in the Norwegian and Swedish Cancer Registries. Standardised incidence ratios (SIRs) were taken as observed numbers of TC/expected numbers of TC in the relatives. The SIR for brothers was 10.2 (95% confidence interval 6.22-15.77). SIR for fathers was 4.3 (1.6-9.3) and for sons 5.7 (0.7-23.2). The point estimate for the risk to brothers in the Norwegian part of the sample to develop TC by the age of 60 was 4.1% (95% CI 1.7-6.6%). This study indicates that genetic factors may be of greater importance in TC than previously assumed. Patients with familial testicular cancer had bilateral tumours more often than sporadic cases (9.8% bilaterality in familial vs 2.8% in sporadic cases, P=0.02). For patients with seminoma age of onset was lower in familial than in sporadic cases (32.9 vs 37.6 years, P=0.06). In father-son pairs, there was a statistically significant earlier age of diagnosis in the generation of sons (28.8 years vs 44.9 years, P=0.04). The prevalence of undescended testis (UDT) did not seem to be higher in familial than in sporadic TC (8.2% in familial TC and 13.3% in sporadic cases). This may indicate that different factors are of importance for the development of familial TC and UDT.
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| 5. |
- Heimdal, K, et al.
(författare)
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Risk of cancer in relatives of testicular cancer patients
- 1996
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Ingår i: British Journal of Cancer. - 0007-0920. ; 73:7, s. 3-970
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of cancer at sites other than the testis has been investigated in the families of 797 Norwegian and 178 Swedish patients diagnosed with testicular cancer during 1981-91. In the families of the Norwegian patients, the total number of cancers in the relatives was significantly lower than the expected number derived from national incidence rates [observed number of cancers 250, expected number of cancers 281.92, standardised incidence ratio (SIR) 0.89, 95% confidence interval (CI) 0.78-1.00]. This finding can be accounted for almost entirely by the finding of fewer than expected prostate and gastrointestinal cancers in the parents of cases. The other common cancers were found at slightly lower than or near the expected levels in the relatives. In the Swedish cohort, which accounts for less than 20% of cases, the observed number of cancers was very close to the expected number. Fourteen fathers of cases had prostate cancer compared with 27.57 prostate cancers expected, giving a SIR of 0.51 (P=0.006). Mothers had more lung cancers (ten cases observed, SIR=2.11, P=0.04) and cancers of the endometrium than expected (13 cases observed, SIR=1.73, P=0.09). These findings may be interpreted as support for theories proposing hormonal dysfunction as causing testicular cancer. Fifty-four gastrointestinal cancers were observed in the parents compared with 68.48 expected (SIR=0.78, P=0.082). Furthermore, testicular cancer was not found to be associated with the known dominantly inherited cancer syndromes [Familial breast (-ovarian) cancer, hereditary no-polyposis colon cancer]. However, one patient belonged to a Li-Fraumeni family, raising the possibility that testicular cancer may be an infrequent component of this rare cancer syndrome. This study supports the hypothesis that families of testicular cancer patients are not prone to cancer.
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| 6. |
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| 7. |
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| 8. |
- Johannsson, Oscar Thor, et al.
(författare)
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Founding BRCA1 Mutations in Hereditary Breast and Ovarian Cancer in Southern Sweden
- 1996
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 58:3, s. 441-450
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Tidskriftsartikel (refereegranskat)abstract
- Nine different germ-line mutations in the BRCA1 breast and ovarian cancer susceptibility gene were identified in 15 of 47 kindreds from southern Sweden, by use of SSCP and heteroduplex analysis of all exons and flanking intron region and by a protein-truncation test for exon 11, followed by direct sequencing. All but one of the mutations are predicted to give rise to premature translation termination and include seven frameshift insertions or deletions, a nonsense mutation, and a splice acceptor site mutation. The remaining mutation is a missense mutation (Cys61Gly) in the zinc-binding motif. Four novel Swedish founding mutations were identified: the nucleotide 2595 deletion A was found in five families, the C 1806 T nonsense mutation in three families, the 3166 insertion TGAGA in three families, and the nucleotide 1201 deletion 11 in two families. Analysis of the intragenic polymorphism D17S855 supports common origins of the mutations. Eleven of the 15 kindreds manifesting BRCA1 mutations were breast-ovarian cancer families, several of them with a predominant ovarian cancer phenotype. The set of 32 families in which no BRCA1 alterations were detected included 1 breast-ovarian cancer kindred manifesting clear linkage to the BRCA1 region and loss of the wild-type chromosome in associated tumors. Other tumor types found in BRCA1 mutation/haplotype carriers included prostatic, pancreas, skin, and lung cancer, a malignant melanoma, an oligodendroglioma, and a carcinosarcoma. In all, 12 of 16 kindreds manifesting BRCA1 mutation or linkage contained ovarian cancer, as compared with only 6 of the remaining 31 families (P < .001). The present study confirms the involvement of BRCA1 in disease predisposition for a subset of hereditary breast cancer families often characterized by ovarian cancers.
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| 9. |
- Kainu, Tommi, et al.
(författare)
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Detection of Germline BRCA1 Mutations in Breast Cancer Patients by Quantitative Messenger RNA in situ Hybridization
- 1996
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Ingår i: Cancer Research. - 1538-7445. ; , s. 2912-2915
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the breast cancer susceptibility gene 1 (BRCA1) may account for one half of all familial breast cancers. Because of the wide spectrum of different germline mutations, identification of BRCA1 mutation carriers using current techniques is laborious and difficult. The majority of the identified mutations, however, lead to aberrant expression of the gene product in tumor tissue, potentially allowing the detection of BRCA1-linked breast cancers using simple histochemical techniques. We performed quantitative mRNA in situ hybridization analysis on archival paraffin-embedded tumor specimens from 25 patients with characterized germline BRCA1 mutations or linkage and from 29 patients with sporadic breast cancers. BRCA1 mRNA levels were invariably low in tumors from BRCA1 mutation carriers. Normal breast epithelium surrounding the BRCA1 tumors showed higher mRNA levels than the tumor tissue, indicating that the low mRNA levels were due to somatic inactivation of the wild-type BRCA1 allele in the tumor tissue. The expression levels in the sporadic tumors were, on average, six times higher than in the BRCA1 tumors (P < 0.0001). The difference allowed identification of BRCA1-mutated and sporadic tumors with more than 95% specificity and sensitivity. We conclude that the analysis of BRCA1 gene expression by mRNA in situ hybridization may be useful in screening for patients with BRCA1-linked breast cancer.
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| 10. |
- Lewold, S, et al.
(författare)
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Overall cancer incidence not increased after prosthetic knee replacement : 14,551 patients followed for 66,622 person-years
- 1996
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Ingår i: International Journal of Cancer. - 0020-7136. ; 68:1, s. 3-30
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Tidskriftsartikel (refereegranskat)abstract
- It is unknown whether patients as a consequence of prosthetic joint replacement are at a higher risk of developing cancer. We therefore analyzed cancer incidence following prosthetic knee replacement (TKR). The observed cancer incidence in 14,551 patients from the population-based Swedish Knee Arthroplasty Register who have undergone TKR because of osteoarthrosis (OA, n = 10,120) or rheumatoid arthritis (RA, n = 4431) were compared with the expected cancer incidence for a Swedish reference population. The cohort was followed for a total of 66,622 person-years. We followed 33% of the patients with OA and 59% of those with RA for more than 5 years. All patients who underwent TKR, whether for OA or for RA, had lower than expected total cancer incidence. We found a markedly low incidence of colorectal carcinoma, especially in patients with RA. Our results do not indicate an increased incidence of cancer following TKR.
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