| 61. |
- Kainu, T, et al.
(author)
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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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In: Proceedings of the National Academy of Sciences. - 1091-6490. ; 97:17, s. 9603-9608
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Journal article (peer-reviewed)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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| 62. |
- Kauraniemi, P, et al.
(author)
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MYB oncogene amplification in hereditary BRCA1 breast cancer
- 2000
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In: Cancer Research. - 1538-7445. ; 60:19, s. 5323-5328
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Journal article (peer-reviewed)abstract
- Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers. Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon.
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| 63. |
- Khan, Tanweera Shaheena, et al.
(author)
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Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients : long-term survival in its adjuvant use
- 2000
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 11:10, s. 1281-1287
-
Journal article (peer-reviewed)abstract
- BACKGROUND:To evaluate the efficacy of streptozocin and o.p'DDD (SO) in adrenocortical cancer (ACC) patients since other chemotherapeutic regimens have limited effects.PATIENTS AND METHODS:We performed a phase II study with SO therapy in 40 ACC patients (median age 44 years). Oral o,p'DDD administration (1-4 g/d, every day) was given together with intravenous streptozocin (1 g/d for five days, thereafter 2 g once every three weeks). 5HT3-receptor blocker was used as standard premedication for streptozocin.RESULTS:The SO therapy was found to have significant effects on disease-free interval (P = 0.02) as well as on survival (P = 0.01) in adjuvantly treated cases (n = 17) in comparison to the patients who did not get any therapy after complete resection (n = 11). Complete or partial response was obtained in 36.4% of patients with measurable disease (n = 22). The overall two-year and five-year survival rates were 70% and 32.5%, respectively. The presence of metastases at diagnosis was identified as a poor prognostic factor (P = 0.02).CONCLUSIONS:The present study necessitates further randomized clinical study of SO therapy in the treatment of ACC, mainly as adjuvant treatment immediately after curative intended surgery, and could be developed into a regular treatment regimen.
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| 64. |
- Koul, A., et al.
(author)
-
BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
- 2000
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In: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 10:4, s. 289-295
-
Journal article (peer-reviewed)abstract
- We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
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| 65. |
- Lagerlund, M, et al.
(author)
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Predictors of non-attendance in a population-based mammography screening programme; socio-demographic factors and aspects of health behaviour
- 2000
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In: European Journal of Cancer Prevention. - : Ovid Technologies (Wolters Kluwer Health). - 0959-8278 .- 1473-5709. ; 9:1, s. 25-33
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Journal article (peer-reviewed)abstract
- The aim of this study was to identify predictors of non-attendance in a population-based mammography-screening programme in central Sweden, on the basis of telephone interviews with 434 non-attendees and 515 attendees identified in a mammography register, Non-attendance was studied in relation to sociodemographic factors, indicators of general health behaviour, self-rated health and experience of cancer in others and own cancer or breast problems. Being single or being non-employed were the only important socio-demographic predictors of non-attendance. Non-attendance was more likely among women who never visited a dentist, had not visited a doctor in 5 years, had never used oral contraceptives or hormone replacement therapy, had never had cervical smear tests, never drank alcohol, smoked regularly, reported no breast cancer in family or friends or own breast problems, We conclude that socio-demographic factors alone do not appear to constitute strong predictors of non-attendance, General health behaviour and previous experience of cancer and breast disease seem to be more important factors. Our results suggest that in the setting of population-based outreach mammography programmes, previous contacts with the health care system and encouragement from health professionals represent determinants of attendance.
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| 66. |
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| 67. |
- Loman, Niklas, et al.
(author)
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Prognosis and clinical presentation of BRCA2-associated breast cancer
- 2000
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In: European Journal of Cancer. - 1879-0852. ; 36:11, s. 1365-1373
-
Journal article (peer-reviewed)abstract
- 54 female breast cancer patients from 22 families with BRCA2 germ line mutations from Sweden and Denmark were compared with 214 age- and date of diagnosis-matched controls identified among breast cancer patients from South Sweden. At diagnosis, BRCA2-associated cases were more often node-positive (N+). OR=1.9 (95% confidence interval (CI)=1.0-3.6; P=0.036), and were more often clinical stage IV: OR=4.6 (95% CI=1.3-17; P=0.021) than the controls. Bilateral disease was also more common among the BRCA2-associated cases: OR=2. 4 (95% CI=1.1-5.3; P=0.027). Breast cancer-specific survival (BCSS) was significantly worse among the BRCA2-associated cases: RR=2.0 (95% CI=1.2-3.4; P=0.010). When stage was corrected for in a multivariate analysis, BCSS was no longer significantly worse for the BRCA2-associated cases: RR=1.6 (95% CI=0.85-3.1). The corresponding effect after correction for bilateral disease was: RR=1.8 (95% CI=1.0-3.1; P=0.034). The unfavourable prognosis in BRCA2-associated breast cancer seems, to a great extent, to be a consequence of the higher clinical stage at diagnosis. The increased presence of bilateral cancers appears to have less impact on survival in this group of hereditary breast cancer. Data presented here needs to be taken into account when counselling healthy carriers of BRCA2 germ line mutations.
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| 68. |
- Lundström, Staffan, et al.
(author)
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Aspects of delayed chemotherapy-induced nausea : Dexamethasone and adrenal response patterns in patients and healthy volunteers
- 2000
-
In: Supportive Care in Cancer. - : Springer. - 0941-4355 .- 1433-7339. ; 8:5, s. 431-434
-
Journal article (peer-reviewed)abstract
- Delayed chemotherapy-induced nausea is still a clinical problem, and the underlying mechanisms are poorly understood. Previous studies have suggested that corticosteroids are involved, although the mechanisms by which corticosteroids exert their anti-emetic effect are largely unknown. We have previously found impaired control of delayed nausea after injection of dexamethasone. The possibility of differences in the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after injection of dexamethasone was investigated in patients (n = 5) with gynaecological cancer being treated with platinum-based chemotherapy and in healthy female volunteers (n = 10). Urinary free cortisol was used to assess the levels of endogenous cortisol. Results showed that in both patients and controls injections of dexamethasone led to a significant decline in endogenous cortisol levels in 24 h and a subsequent significant recovery in the next 24 h. We conclude that the recovery of the HPA axis is rapid after a single dose of dexamethasone in patients and controls. The absence of an abnormal response pattern in patients makes it probable that the suppression and recovery of the HPA axis after injection of dexamethasone does not influence the corticosteroid-induced rebound effect on delayed platinum-induced nausea.
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| 69. |
- Manjer, Jonas, et al.
(author)
-
Breast cancer incidence in relation to smoking cessation
- 2000
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In: Breast Cancer Research and Treatment. - 1573-7217. ; 61:2, s. 121-129
-
Journal article (peer-reviewed)abstract
- High plasma levels of oestrogens are associated with increased breast cancer risk. If smoking, as has been suggested, have both a tumour initiating mutagenic effect and a protective anti-oestrogenic effect, one would assume that smokers who give up smoking have the highest incidence of breast cancer. This was evaluated in the follow-up of a cohort of 10,902 women of whom 4,359 were premenopausal. Record-linkage with official cancer registries yielded 416 incident cases during an average follow-up of 13.6 years. The adjusted relative risk in all ex-smokers was 1.31 (1.02-1.69), as compared to never smokers, and in premenopausal ex-smokers it was 1.57 (1.07-2.30). Breast cancer incidence in premenopausal ex-smokers was inversely related to time since cessation, (p for trend = 0.01), and was highest among the women who had given-up smoking less than 12 months before screening: 2.76 (1.55-4.91). There was no significant association between current smoking and breast cancer risk. We conclude that incidence of breast cancer in premenopausal women who have given up smoking is higher than it is in smokers and never smokers. To what extent this may be related to endocrine effects associated with smoking cessation remains to be evaluated.
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| 70. |
- Manjer, Jonas, et al.
(author)
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Intra-urban differences in breast cancer mortality: a study from the city of Malmo in Sweden
- 2000
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In: Journal of Epidemiology and Community Health. - : BMJ. - 1470-2738 .- 0143-005X. ; 54:4, s. 279-285
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Journal article (peer-reviewed)abstract
- STUDY OBJECTIVE: To assess whether in an urban population stage at breast cancer diagnosis is related to area of living and to what extent intra-urban differences in breast cancer mortality are related to incidence respectively stage at diagnosis. DESIGN: National registries were used to identify cases. Mortality in 17 residential areas was studied in relation to incidence and stage distribution using linear regression analysis. Areas with high and low breast cancer mortality, incidence and proportion of stage II+ tumours at diagnosis were also compared in terms of their sociodemographic profile. SETTING: City of Malmo in southern Sweden. PATIENTS: The 1675 incident breast cancer cases and 448 deaths that occurred in women above 45 years of age in Malmo 1986-96. MAIN RESULTS: Average annual age standardised breast cancer mortality ranged between residential areas, from 35/10(5) to 107/10(5), p = 0.04. Mortality of breast cancer was not correlated to incidence, r = 0.22, p = 0.39. The ratio of stage II+/0-I cancer incidence varied between areas from 0.45 to 1.99 and was significantly correlated to breast cancer mortality, r = 0.53, p = 0.03. Areas with high proportion of stage II+ cancers and high mortality/incidence ratio were characterised by a high proportion of residentials receiving income support, being foreigners and current smokers. CONCLUSIONS: Within this urban population there were marked differences in breast cancer mortality between residential areas. Stage at diagnosis, but not incidence, contributed to the pattern of mortality. Areas with high proportion of stage II+ tumours differed unfavourably in several sociodemographic aspects from the city average.
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