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- Bratt, O, et al.
(author)
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Sons of men with prostate cancer : their attitudes regarding possible inheritance of prostate cancer, screening, and genetic testing
- 1997
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In: Urology. - 0090-4295. ; 50:3, s. 5-360
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To study attitudes regarding possible inheritance of prostate cancer among sons of men with prostate cancer.METHODS: A questionnaire was sent to 69 men with prostate cancer and their 101 unaffected sons. All participants were also interviewed by telephone. Sociodemographic data were collected, as were data about the fathers' disease.RESULTS: The response rate was high; 100 sons (99%) and 65 fathers (94%) answered all questions. Sixty of the sons claimed they had worries about having an increased risk of prostate cancer due to possible inheritance. About 90% of the sons wanted to know whether prostate cancer was inheritable (66 definitely and 24 probably), were positively inclined to undergo screening (65 definitely and 27 probably), and to undergo genetic testing (50 definitely and 41 probably), provided there had been multiple cases of prostate cancer in their family. An interest to know whether prostate cancer could be inherited was more frequent among sons with less than 12 years of education, worries about inheritance, younger age, a father treated with curative intent, and with children of their own, especially if sons. Interest in genetic testing was associated with less than 12 years of education and with worries about inheritance.CONCLUSIONS: A large majority of healthy men with a family history of prostate cancer were interested in knowing whether the disease could be inherited and were positively inclined to undergo screening and genetic testing. Our findings indicate that genetic counseling and a screening program could have beneficial psychological effects in families with multiple cases of prostate cancer.
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2. |
- Bratt, O, et al.
(author)
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The risk of malignant tumours in first-degree relatives of men with early onset prostate cancer : a population-based cohort study
- 1997
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In: European Journal of Cancer. - 0959-8049. ; 33:13, s. 2237-2240
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Journal article (peer-reviewed)abstract
- Previous studies have indicated that hereditary prostate cancer is common among men with early onset prostate cancer. The aim of this study was to investigate the incidence of malignant tumours in first-degree relatives of men with early onset prostate cancer. All prostate cancer cases diagnosed before the age of 51 years from 1958 to 1994 were identified in the population-based Swedish Cancer Register. The first-degree relatives of clinical cases were identified through parish data. Their vital status and cancer incidence were studied in the Swedish Cancer Register, the Cause of Death Register and the Census Register. The expected incidence of malignant tumours for the first-degree relatives were calculated using regional cancer register data. Cause-specific standardised incidence ratios (SIR) and 95% confidence intervals (CI) were calculated. The study included 423 first-degree relatives of 89 men with clinical prostate cancer. The first-degree relatives' SIR for malignant tumours was 0.99 (95% CI 0.78-1.23). The SIR for prostate cancer diagnosed at any age was 1.43 (95% CI 0.82-2.33), and 3.37 for first-degree relatives diagnosed before the age of 70 years (95% CI 1.36-6.94). There was no significantly increased risk of any non-prostatic malignant tumour. Only in five of the families did the pedigree show a pattern of hereditary prostate cancer. The first-degree relatives of men with early onset prostate cancer had more than a 3-fold increase in the risk of developing prostate cancer before the age of 70 years, but their total cancer risk was not increased. This study does not support the assumption that dominantly inherited susceptibility is a major cause of early onset prostate cancer.
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4. |
- Hakansson, Sara, et al.
(author)
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Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
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In: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
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Journal article (peer-reviewed)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
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5. |
- Heimdal, K, et al.
(author)
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A segregation analysis of testicular cancer based on Norwegian and Swedish families
- 1997
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In: British Journal of Cancer. - 0007-0920. ; 75:7, s. 7-1084
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Journal article (peer-reviewed)abstract
- Clustering of testicular cancer cases in families is well known, although the aetiology is not. We present the results of a segregation analysis performed with the algorithm Pointer on familial data on 978 Scandinavian patients with testicular cancer. The segregation analysis favoured the involvement of major gene effects over models incorporating solely polygenic effects in testicular cancer aetiology. Overall, a recessive model best fits the family observations with an estimated gene frequency of 3.8% and a lifetime risk for homozygous men of developing the disease of 43%. This implies that 7.6% of men in the general population will be carriers of the mutant allele and that 0.1% would be homozygote and are, therefore, at high risk of developing the cancer. The testicular cancer incidence has changed greatly during the last generation. Also, the lethality of the disease has changed because of the introduction of new therapy. As failure to take account of such time trends might lead to inappropriate evidence for a recessive model, the analyses were repeated under different assumptions. The analyses favoured a recessive model of inheritance under all assumptions tested. However, the assumptions underlying the analyses are complex and, as this is the first segregation analysis of testicular cancer, the results must be interpreted cautiously.
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7. |
- Jernström, Helena, et al.
(author)
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Reduced testosterone, 17 beta-oestradiol and sexual hormone binding globulin, and increased insulin-like growth factor-1 concentrations, in healthy nulligravid women aged 19-25 years who were first and/or second degree relatives to breast cancer patients
- 1997
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In: European Journal of Cancer Prevention. - 1473-5709. ; 6:4, s. 330-340
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Journal article (peer-reviewed)abstract
- Differences in hormonal and constitutional parameters between women with at least one first and/or second degree relative with breast cancer (RBC) and women without such affected relatives were studied in a group of healthy, nulligravid women aged 19-25 years. Present oral contraceptive (OC) users were analysed separately. In women not presently exposed to OCs we found significant correlations between RBC and reduced concentrations of testosterone during both the follicular (P < 0.001) and luteal menstrual cycle phases (P = 0.016). 17 beta-oestradiol was also significantly negatively correlated with RBC in the follicular (P = 0.044) and in the luteal phase (P = 0.027). RBC was significantly correlated with a lower waist/hip ratio (P = 0.044) compared with women without such a history. In multivariate analyses, the results for testosterone but not 17 beta-oestradiol remained significant. In these analyses high IGF-1 (P = 0.05) in the follicular phase and low sexual hormone-binding globulin (SHBG) (P = 0.04) in the luteal phase were also related to RBC. Including all 66 women in a multivariate model that analysed the specific effects from OCs and RBC on plasma testosterone showed that plasma testosterone was significantly lower among present OC users (P = 0.004) and in women with RBC (P = 0.005) during cycle days 5-10, with a significant positive two-way interaction between present OC use and RBC (P = 0.007). During cycle days 18-23 plasma testosterone showed a significant negative relationship with present OC use (P < 0.001) and RBC (P = 0.016) no significant interaction was seen during cycle days 18-23. Factors not significantly related to RBC were height, weight, breast size, age at menarche, p-progesterone and p-prolactin. It is concluded that a family history of breast cancer significantly lowered plasma testosterone concentrations in both cycle phases among healthy, nulligravid women compared with women without such history.
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8. |
- Johannsson, Oscar Thor, et al.
(author)
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Tumor Biological Features of BRCA1-Induced Breast Cancer
- 1997
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In: European Journal of Cancer. - 1879-0852. ; 33:3, s. 362-371
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Journal article (peer-reviewed)abstract
- BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison group of stage II breast cancers were studied with regard to histopathological features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often DNA non-diploid, as well as being characterised by higher S-phase fraction values. These results suggest that BRCA1-induced breast cancers may manifest distinct tumour biological features of clinical importance.
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9. |
- Jóhannsson, O T, et al.
(author)
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Tumour biological features of BRCA1-induced breast and ovarian cancer
- 1997
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In: European Journal of Cancer. - 0959-8049. ; 33:3, s. 362-371
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Journal article (peer-reviewed)abstract
- BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison group of stage II breast cancers were studied with regard to histopathological features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often DNA non-diploid, as well as being characterised by higher S-phase fraction values. These results suggest that BRCA1-induced breast cancers may manifest distinct tumour biological features of clinical importance.
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