| 1. |
- Brandt, Andreas, et al.
(författare)
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Age at Diagnosis and Age at Death in Familial Prostate Cancer
- 2009
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 14:12, s. 1209-1217
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. A family history of prostate cancer is associated with a higher risk for prostate cancer to first-degree relatives. If greater surveillance of men at familial risk is considered to be useful, population-based estimates of the differences in the age at diagnosis between familial and sporadic prostate cancer cases are needed. Methods. The men in the nationwide Swedish Family-Cancer Database were classified according to the number and type of affected first-degree relatives (father or brother) and according to the relative's age at diagnosis. The cumulative incidence of prostate cancer and cumulative prostate cancer-specific mortality were estimated using a stratified Cox model. Results. The cumulative incidence was highest for men with multiple affected first-degree relatives, and it was higher for brothers than for sons of prostate cancer patients. The age to reach the same cumulative incidence as the general population at age 55 years decreased with decreasing age at diagnosis of the relative, ranging from 48.7 years (father diagnosed before 60 years of age) to 53.7 years (father diagnosed after 82 years of age). Prostate cancer-specific mortality was also related to the number and type of affected relatives but there was no clear evidence for a dependency on the age at diagnosis of the relative. Conclusions. Men with a father or a brother affected by prostate cancer are diagnosed and die at earlier ages than men without a family history of prostate cancer. This study should encourage further analysis in order to assess the risks and benefits of screening for prostate cancer in men at higher risk. The Oncologist 2009; 14: 1209-1217
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| 2. |
- Brandt, Andreas, et al.
(författare)
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Age-Specific Risk of Incident Prostate Cancer and Risk of Death from Prostate Cancer Defined by the Number of Affected Family Members
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 58:2, s. 275-280
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Tidskriftsartikel (refereegranskat)abstract
- Background: The thorough assessment of familial prostate cancer (PCa) risk is as important as ever to provide a basis for clinical counselling and screening recommendations. Objective: Our aim was to determine the age-specific risks of PCa and the risk of death from PCa according to the number and the age of affected first-degree relatives. Design, setting, and participants: The nationwide Swedish Family-Cancer Database includes a record of >11.8 million individuals and their cancers from 1958 to 2006. All men from the database with identified parents (>3.9 million individuals) were followed between 1961 and 2006. The study included 26 651 PCa patients, of whom 5623 were familial. Measurements: The age-specific hazard ratios (HRs) of PCa and the HRs of death from PCa were calculated according to the number and age of affected fathers and brothers. Results and limitations: The HRs of PCa diagnosis increased with the number of affected relatives and decreased with increasing age. The highest HRs were observed for men <65 yr of age with three affected brothers (HR: approximately 23) and the lowest for men between 65 and 74 yr of age with an affected father (HR: approximately 1.8). The HRs increased with decreasing paternal or fraternal diagnostic age. The pattern of the risk of death from familial PCa was similar to the incidence data. Conclusions: The present results should guide clinical counselling and demonstrate the vast increases in risk when multiple first-degree relatives are affected. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 3. |
- Brandt, Andreas, et al.
(författare)
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Breast cancer risk in women who fulfill high-risk criteria: at what age should surveillance start?
- 2010
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 121:1, s. 133-141
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Tidskriftsartikel (refereegranskat)abstract
- Family history is a strong predictor of hereditary breast cancer, particularly when it includes cases of early onset or bilateral breast cancers and multiple cases of breast or ovarian cancers. This article provides relative risks and cumulative risks of breast cancer in women whose family history indicates high risk. Specifically, the aim was to determine how many years earlier the high-risk women reach the cumulative risk of women without family history at the age at which screening in average-risk women is initiated. The women of the nation-wide Swedish Family-Cancer Database were classified according to clinical criteria based on family history suggesting high risk for hereditary breast ovarian cancer syndrome. The relative risks of breast cancer were calculated as hazard ratio using Cox regression. Cumulative risks of breast cancer were estimated with a stratified Cox model based on Tsiatis' method. The hazard ratios of breast cancer for the considered criteria ranged from 1.50 to 5.99. The cumulative risks ranged from 1 to 10% by age 50 years. The age to reach the same cumulative risk as women lacking a family history at the age of 50 years ranged between 32.0 and 40.8 years. Relative and cumulative risks of women at high risk of breast cancer associated with different clinical criteria were diverse, which may be helpful in considering when current clinical criteria are revised. According to the present results, current recommendations of starting clinical interventions 10 years earlier in high-risk women, based on expert opinions, appear justified at least for the largest high-risk groups.
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| 4. |
- Brandt, Andreas, et al.
(författare)
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Familial risks of breast and prostate cancers: Does the definition of the at risk period matter?
- 2010
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 46:4, s. 752-757
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Tidskriftsartikel (refereegranskat)abstract
- Aim: 'Being at familial risk' may have different connotations in studies on familial risk of cancer. The register-based definition of a family history considers individuals with an affected relative at familial risk independently of the family member's diagnostic time. Alternatively, the individuals are classified to be at familial risk only after the diagnosis date of their relative, relevant to clinical counselling and screening situations. The aim of this study was to compare familial breast and prostate cancer risks according to the two definitions. Patients and methods: The nationwide Swedish Family-Cancer Database with information on cancers from 1958 to 2006 was used to calculate the hazard ratio of breast and prostate cancers according to family history using Cox regression. Family history was defined considering the number and type of affected relatives and the relative's diagnostic age, respectively. Individuals were considered at familial risk from their entry to the study or, alternatively, from the diagnostic time of the relative. Results: Hazard ratios were equal whether individuals were considered at risk independent of the relative's diagnostic date or only after the relative's diagnostic date. Conclusion: These results indicate that studies on familial breast or prostate cancer risk which do not take the relative's diagnosis date into account are applicable to screening and clinical counselling situations. The estimates according to the register-based definition are based on larger numbers of patients, which may be crucial for analysis of small groups such as families of multiple cases. (C) 2009 Elsevier Ltd. All rights reserved.
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| 5. |
- Brandt, Andreas, et al.
(författare)
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Risk of incident and fatal melanoma in individuals with a family history of incident or fatal melanoma or any cancer.
- 2011
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 165, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- Background: A family history of melanoma is associated with an increased risk of melanoma and probably of other, discordant cancers. Limited data are available on familial mortality in melanoma. If fatal forms of melanoma were associated with fatal forms of melanoma or of some other cancers, only studies on familial mortality rather than on familial incidence might be able to detect them. Furthermore, estimates on familial aggregation based on mortality are free from bias of overdiagnosis. Objectives: The aim of this study was the estimation of familial aggregation of concordant melanoma and of melanoma and any other cancers both based on incidence and mortality. Methods: We used the nation-wide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIR) for incident melanoma for relatives of any cancer patients and standardized mortality ratios (SMR) for death in melanoma for relatives of individuals who died from any other cancer. Similar risks were determined for any common cancer when relatives were affected by melanoma. Results: For concordant melanoma, familial incidence equalled familial mortality, SIR=SMR. Familial clustering (SIRs increased) of melanoma and esophageal, colorectal, breast, prostate, kidney, nervous system and connective tissue cancers and myeloma and leukaemia was observed. The SMRs for pancreatic and nervous system cancers were increased in relatives whose parents had died from melanoma. Conclusions: These data should encourage search for fatal subtypes of familial cancer, which may eventually have clinical implications.
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| 6. |
- Brendle, Annika, et al.
(författare)
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Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer ITGB4 as prognostic marker.
- 2008
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1394-1399
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Tidskriftsartikel (refereegranskat)abstract
- Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.
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| 7. |
- Brendle, Annika, et al.
(författare)
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Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer : a Swedish prospective case-control study.
- 2009
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Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 45:3, s. 435-442
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal instability (CIN) is a major characteristic of many cancers. We investigated whether putatively functional single nucleotide polymorphisms (SNPs) in genes related to CIN (CENPF, ESPL1, NEK2, PTTG1, ZWILCH, ZWINT) affect breast cancer (BC) risk and clinical outcome in a Swedish cohort of 749 incident BC cases with detailed clinical data and up to 15 years of follow-up and 1493 matched controls. As a main observation, carriers of the A allele of the CENPF SNP rs438034 had a worse BC-specific survival compared to the wild type genotype GG carriers (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.90), although they were less likely to have regional lymph node metastases (odds ratio (OR) 0.71, 95% CI 0.51-1.01) and tumours of stage II-IV (OR 0.73, 95% CI 0.54-0.99). As there is increasing evidence that CENPF is associated with poor prognosis in patients with primary BC, further independent studies are needed to clarify the importance of genetic variation in the CENPF gene in the clinic.
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| 8. |
- Hemminki, Kari, et al.
(författare)
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Do discordant cancers share familial susceptibility?
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48, s. 1200-1207
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cancer syndromes manifest at many sites albeit with variable penetrance. Genome-wide association (GWA) studies have identified susceptibility loci shared by many types of cancer. Yet, a population level search for shared susceptibility between discordant cancers has been hampered because of lacking population sizes. METHODS: Over 1.1million patients in the nation-wide Swedish Family-Cancer Database were analysed for discordant familial cancers covering 33 sites. Standardised incidence ratios (SIRs) were calculated for patients whose family members had a defined cancer compared to those whose family members did not have that cancer. Three independent tests for each pair of cancer sites were done using different family relationships. RESULTS: Lung cancer showed 13 significant discordant associations but most of them were with sites for which smoking is a risk factor. An exception was the clustering of lung cancer and endocrine cancers. Four discordant associations reached a minimal significance level of 5×10(-6): colorectum-endometrium, breast-ovary, breast-prostate and melanoma-squamous cell carcinoma of the skin. The association of melanoma and nervous system cancer reached a minimal significance of 10(-4). Discarding lung cancer, all other associations were based on a single test whereby they were liable to be chance associations. CONCLUSIONS: This study showed the extraordinary requirements for statistical power in study of multiple cancer sites. In addition to the smoking related sites, associations between breast and prostate cancers, melanoma and nervous system tumours and lung and endocrine tumours found strong statistical support. Within the present sample size limits, we found no evidence of an overall susceptibility to cancer.
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| 9. |
- Hemminki, Kari, et al.
(författare)
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Does the Breast Cancer Age at Diagnosis Differ by Ethnicity? A Study on Immigrants to Sweden
- 2011
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 16:2, s. 146-154
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Tidskriftsartikel (refereegranskat)abstract
- Background. Age-specific incidence rates for breast cancer in low-risk and high-risk ethnic populations differ by age at which the incidence maximum is reached: around 50 years in low-risk populations and over 60 years in high-risk populations. The interpretation of these differences remains unsettled, one line primarily referring to biological differences, the second one to cohort effects of rapidly increasing rates in young populations, and the third one to incomplete registration of cancer in the elderly. Methods. The nationwide Family-Cancer Database was used to analyze standardized incidence ratios (SIRs) and age at diagnosis of breast cancer in female immigrants to Sweden by their region of origin compared with women native to Sweden matched on birth year and other relevant factors. Results. We showed first that the SIRs for breast cancer were lower in many immigrant groups compared with natives of Sweden; women from Turkey had the lowest SIR of 0.45, followed by those from Chile (0.54) and Southeast Asia (0.57). Women from nine regions showed an earlier mean age at diagnosis than their matched Swedish controls, the largest differences being 5.5 years for women from Turkey, 5.1 years for those from Asian Arab and "Other African" countries, 4.3 years for those from Iran, and 4.0 years for those from Iraq. Conclusions. The results show that in many immigrant groups, the diagnostic age is earlier (< 50 years) than in natives of Sweden (> 50 years), suggesting that true biological factors underlie the differences. These factors may explain much of the international variation in breast cancer incidence. Identifying these factors should advance understanding of breast cancer etiology and prevention. The Oncologist 2011; 16: 146-154
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| 10. |
- Hemminki, Kari, et al.
(författare)
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Familial Mortality and Familial Incidence in Cancer.
- 2011
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 29, s. 712-718
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE An overwhelming majority of data on familial risk in cancer is based on incident cancer, whereas familiality in cancer mortality is largely unknown. If fatal form of cancer was a highly familial subtype, then familial risk for mortality may exceed that of incidence, which would be particularly relevant for clinical decision making and counseling. PATIENTS AND METHODS The individuals in the nationwide Swedish Family-Cancer Database were classified according to family history of fatal and nonfatal cancer. Familial risks of incident and fatal concordant cancer were calculated for offspring based on their parental family history using a Cox model with hazard ratio (HR); offspring without family history were the reference. Results Most HRs for offspring incident cancers were somewhat higher for fatal compared with nonfatal parental family history. For breast (HR, 1.87 fatal v 1.66 nonfatal; P < .001) and prostate (HR, 2.30 fatal v 1.84 nonfatal; P < .001) cancers, 51.0% of patients with familial breast cancer and 56.6% of patients with prostate cancer had fatal family history. HRs for death in offspring according to a fatal compared with nonfatal family history were significantly increased for colorectal (HR, 1.76 v 1.47, respectively; P = .02), breast (HR, 1.97 v 1.51, respectively; P = .002), and prostate (HR, 2.03 v 1.59, respectively; P = .002) cancers. TNM classification did not seem to differ between the family histories. We showed also that an overwhelming proportion of offspring were diagnosed after the parental death. CONCLUSION Familial breast, prostate, and colorectal cancers might have a yet unidentified genetic component associated with poorer survival. It may be useful to record survival data in family history records.
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