| 1. |
- Bermejo, Justo Lorenzo, et al.
(författare)
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Age-time risk patterns of solid cancers in 60 901 non-Hodgkin lymphoma survivors from Finland, Norway and Sweden
- 2014
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 164:5, s. 675-683
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Tidskriftsartikel (refereegranskat)abstract
- Survival after non-Hodgkin lymphoma (NHL) has increased thanks to improved treatment but NHL survivors have an increased risk of second neoplasms. The assessment of cancer risk patterns after NHL may help to quantify the late side-effects of therapy. Poisson regression was used to estimate relative risks (RRs) and absolute incidence rates for nine solid tumours based on a nationwide cohort of 60 901 NHL survivors from Finland, Norway and Sweden. Patients were diagnosed between 1980 and 2006 and developed 6815 s neoplasms. NHL patients showed an increased risk of each of the nine investigated cancer sites: prostate and pancreas (both RRs 1.28), breast (1.37), colorectum (1.48), urinary bladder (1.52), stomach and lung (both RRs 1.87), skin (melanoma 2.27) and kidney (2.56). The RRs showed a U-shaped relationship with time after NHL for all nine-second cancer types. NHL diagnosis early in life was a risk factor for the development of second cancers with the exception of melanoma, but a risk excess was even observed in patients diagnosed with NHL at age 80+ years. The present study provides accurate estimates on the adverse late effects of NHL therapy, which should guide the establishment of cancer prevention strategies in NHL survivors.
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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. |
- de Verdier, Petra J., et al.
(författare)
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Genotypes, haplotypes and diplotypes of three XPC polymorphisms in urinary-bladder cancer patients
- 2010
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Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 694:1-2, s. 39-44
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The XPC gene is involved in DNA damage recognition in the nucleotide excision repair pathway (NER) We investigated the additive effects of single nucleotide polymorphisms (SNPs) in bladder-cancer patients and population controls for three XPC polymorphisms A499V (C>T) K939Q (A>C) and poly AT (PAT -/+) Experimental Design 311 bladder-cancer patients from a population-based cohort and 337 population controls were genotyped using the PCR-restriction fragment length polymorphism (RFLP) technique Results We found complete linkage between the K939Q (A>C) and PAT (-/+) polymorphisms and therefore only the K939Q (A>C) polymorphism was included in analyses The over all estimated odds ratio was 1 7 (95% CI 1 3-2 4) for A499V (C>T) and 1 4 (95% CI 1 0-2 0) for K939Q (A>C) The associated odds ratio Increase with the variant allele homozygotes was six-fold for the A499V (C>T) and three-fold for the K939Q (A>C) polymorphism (OR=5 7 95% CI 3 4-9 5 and OR=2 6 95% CI 1 3-5 6 respectively) The variant allele haplotype of the two polymorphisms (T499C939) was associated with a nearly four fold increased odds ratio compared to the common allele haplotype (C(499)A(939)) (OR=3 6 95% Cl 1 9-6 9) Combined genotype analysis showed an Increased disease association with increasing number of variant alleles (p<0 0001) with a dominant effect of the A499V polymorphism In addition we observed association of the disease with increasing number of variant alleles for the A499V polymorphism and an early age at diagnosis (p=0 004) Conclusions Our results suggest an association between the XPC genotypes of the A499V K939Q and PAT polymorphisms and urinary-bladder cancer We propose a poly-allelic effect of these polymorphisms where the cumulative effect on disease becomes higher than the individual allelic effects (C) 2010 Elsevier B V All rights reserved
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| 8. |
- Hemminki, Kari, et al.
(författare)
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Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes
- 2010
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Old age at diagnosis is associated with poor survival in colorectal cancer (CRC) for unknown reasons. Recent data show that colonoscopy is efficient in preventing left-sided cancers only. We examine the association of Tumor Node Metastasis (TNM) classes with diagnostic age and patient characteristics. Methods: The Swedish Family-Cancer Database has data on TNM classes on 6,105 CRC adenocarcinoma patients. Ordinal logistic regression analysis was performed to model tumor characteristics according to age at diagnosis, tumor localization, gender, socioeconomic status, medical region and family history. The results were compared to results from survival analysis. Results: The only parameters systematically associated with TNM classes were age and tumor localization. Young age at diagnosis was a risk factor for aggressive CRC, according to stage, N and M with odds ratios (ORs) ranging from 1.80 to 1.93 for diagnosis before age 50 years compared to diagnosis at 80+ years. All tumor characteristics, particularly T, were worse for colon compared to rectal tumors. Right-sided tumors showed worse characteristics for all classifiers but M. The survival analysis on patients diagnosed since 2000 showed a hazard ratio of 0.55 for diagnosis before age 50 years compared to diagnosis at over 80 years and a modestly better prognosis for left-sided compared to right-sided tumors. Conclusions: The results showed systematically more aggressive tumors in young compared to old patients. The poorer survival of old patients in colon cancer was not related to the available tumor characteristics. However, these partially agreed with the limited colonoscopic success with right-sided tumors.
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| 9. |
- Lorenzo Bermejo, Justo, et al.
(författare)
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Comparison of Six Statistics of Genetic Association Regarding Their Ability to Discriminate between Causal Variants and Genetically Linked Markers
- 2011
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Ingår i: Human Heredity. - : S. Karger AG. - 1423-0062 .- 0001-5652. ; 72:2, s. 142-152
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Genome-wide association (GWA) studies still rely on the common-disease common-variant hypothesis since the assumption is associated with increased power. In GWA studies, polymorphisms are genotyped and their association with disease is investigated. Most of the identified associations are indirect and reflect a shared inheritance of the genotyped markers and genetically linked causal variants. We have compared six statistics of genetic association regarding their ability to discriminate between markers and causal susceptibility variants, including a probability value (Pval) and a Bayes Factor (BF) based on logistic regression, and the attributable familial relative risk (FRR). Methods: We carried out a simulation-based sensitivity analysis to explore several conceivable scenarios. Theoretical results were illustrated by established causal associations with age-related macular degeneration and by using imputed data based on HapMap for a case-control study of breast cancer. Results: Our data indicate that a representation of genetic association by FRRs and BFs generally facilitates the distinction of causal variants. The FRR showed the best discriminative power under most investigated scenarios, but no single statistic outperformed the others in all situations. For example, rare moderate-to low-penetrance variants (allele frequency: 1%, dominant odds ratio: <= 2.0) seem to be best discriminated by BFs. Conclusions: Present results may help to fully utilize the data generated in association studies that take advantage of next generation sequencing and/or multiple imputation based on the 1000 Genomes Project. Copyright (C) 2011 S. Karger AG, Basel
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| 10. |
- Maccioni, Livia, et al.
(författare)
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Variants at chromosome 20 (ASIP locus) and melanoma risk
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 132:1, s. 42-54
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Tidskriftsartikel (refereegranskat)abstract
- Agouti signaling protein (ASIP) locus on chromosome 20q11 is implicated, as shown by genome-wide association studies, in phenotype variation and melanoma risk. We genotyped 837 melanoma cases and 1,154 controls for 21 single nucleotide polymorphisms (SNPs) informative for 495 polymorphisms at the locus. Our data showed an increased risk of melanoma (odds ratio [OR] 1.27, 95% confidence interval [95% CI] 1.03-1.57) in carriers of the rs4911414 variant, located 120 kb upstream of ASIP. The main effect of rs4911414, as reported previously, was in tandem with a 10 kb adjacent polymorphism rs1015362; two constituted risk-associated haplotype/diplotype. Except for rs1015363, none of the 12 tagging SNPs, genotyped to cover 239.9 kb region with polymorphisms linked to rs4911414 and rs1015362, were associated with melanoma. Our data confirmed a previous association of melanoma risk (OR 1.82, 95% CI 1.37-2.41) with rs4911442, located in intron 5 of the nuclear receptor coactivator 6 (NCOA6) gene. The rs910871, one of the six variants, genotyped to cover NCOA6, showed an association with melanoma risk (OR 1.33, 95% CI 1.04-1.70). Both, rs4911442 and rs910871 were in moderate linkage with a, previously reported, risk-associated rs910873 polymorphism. A haplotype from the variants within NCOA6 showed an association with risk of melanoma (OR 1.49, 95% CI 1.17-1.88). Interaction between risk-associated polymorphisms and previously genotyped melanocortin receptor 1 (MC1R) variants, in our study, was not statistically significant. Nevertheless, the carriers of the variant alleles over the background of MC1R variants were at a higher risk than the carriers not enriched for MC1R variants. Our data confirmed the association of different variants at chromosome 20q11 with melanoma risk.
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