| 21. |
- Brandt, Andreas, et al.
(författare)
-
Age-Specific Risk of Incident Prostate Cancer and Risk of Death from Prostate Cancer Defined by the Number of Affected Family Members
- 2010
-
Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 58:2, s. 275-280
-
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.
|
|
| 22. |
- Brandt, Andreas, et al.
(författare)
-
Breast cancer risk in women who fulfill high-risk criteria: at what age should surveillance start?
- 2010
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 121:1, s. 133-141
-
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.
|
|
| 23. |
- Brandt, Andreas, et al.
(författare)
-
Familial risks of breast and prostate cancers: Does the definition of the at risk period matter?
- 2010
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 46:4, s. 752-757
-
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.
|
|
| 24. |
- Brandt, A., et al.
(författare)
-
Risk for incident and fatal prostate cancer in men with a family history of any incident and fatal cancer
- 2012
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:1, s. 98-251
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Familial clustering of incident prostate cancer and some cancers at other discordant sites has been reported. Less is known about familial clustering of fatal prostate cancer with any fatal discordant cancers. Estimates on familial aggregation based on mortality are free from bias of overdiagnosis. Patients and methods: We used the nationwide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for incident prostate cancer for relatives of patients with any common cancer and standardized mortality ratios (SMRs) for death in prostate cancer for relatives of individuals who died from cancer. Similar risks were determined for any common cancer when relatives were affected by prostate cancer. Results: We observed familial aggregation of incident and fatal prostate cancers. Familial clustering (SIRs increased) of prostate cancer and of cancers at discordant sites was found for breast, ovarian, and kidney cancers and melanoma. Also, fatal prostate cancer clustered with these and cervical cancers (SMRs increased). Conclusions: Our findings demonstrate that familial aggregation of prostate and breast cancers are not due to shared screening habits. The data on the association of cancers at discordant sites might be useful for clinical counseling and for mechanistic studies searching explanations to the familial clustering between discordant cancers.
|
|
| 25. |
- Brandt, Andreas, et al.
(författare)
-
Risk of incident and fatal melanoma in individuals with a family history of incident or fatal melanoma or any cancer.
- 2011
-
Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 165, s. 342-348
-
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.
|
|
| 26. |
- Broderick, Peter, et al.
(författare)
-
Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:1, s. 58-83
-
Tidskriftsartikel (refereegranskat)abstract
- To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 x 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 x 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 x 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights.
|
|
| 27. |
- Caliz, Rafael, et al.
(författare)
-
Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
-
Tidskriftsartikel (refereegranskat)abstract
- The present study was conducted to explore whether single nucleotide polymorphisms (SNPs) in Th1 and Th17 cell-mediated immune response genes differentially influence the risk of rheumatoid arthritis (RA) in women and men. In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP-1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of Dectin-2(rs4264222T) allele had an increased risk of RA (OR = 1.47, 95% CI 1.10-1.96) whereas patients harboring the DC-SIGN(rs4804803G), MCP-1(rs1024611G), MCP-1(rs13900T) and MCP-1(rs4586C) alleles had a decreased risk of developing the disease (OR = 0.66, 95% CI 0.49-0.88; OR = 0.66, 95% CI 0.50-0.89; OR = 0.73, 95% CI 0.55-0.97 and OR = 0.68, 95% CI 0.51-0.91). Interestingly, significant gender-specific differences were observed for Dectin-2(rs4264222) and Dectin-2(rs7134303): women carrying the Dectin-2(rs4264222T) and Dectin-2(rs7134303G) alleles had an increased risk of RA (OR = 1.93, 95% CI 1.34-2.79 and OR = 1.90, 95% CI 1.29-2.80). Also five other SNPs showed significant associations only with one gender: women carrying the MCP-1(rs1024611G), MCP-1(rs13900T) and MCP-1(rs4586C) alleles had a decreased risk of RA (OR = 0.61, 95% CI 0.43-0.87; OR = 0.67, 95% CI 0.47-0.95 and OR = 0.60, 95% CI 0.42-0.86). In men, carriers of the DC-SIGN(rs2287886A) allele had an increased risk of RA (OR = 1.70, 95% CI 1.03-2.78), whereas carriers of the DC-SIGN(rs4804803G) had a decreased risk of developing the disease (OR = 0.53, 95% CI 0.32-0.89). In phase 2, we genotyped these SNPs in 754 RA patients and 519 controls, leading to consistent gender-specific associations for Dectin-2(rs4264222), MCP-1(rs1024611), MCP-1(rs13900) and DC-SIGN(rs4804803) polymorphisms in the pooled sample (OR = 1.38, 95% CI 1.08-1.77; OR = 0.74, 95% CI 0.58-0.94; OR = 0.76, 95% CI 0.59-0.97 and OR = 0.56, 95% CI 0.34-0.93). SNP-SNP interaction analysis of significant SNPs also showed a significant two-locus interaction model in women that was not seen in men. This model consisted of Dectin-2(rs4264222) and Dectin-2(rs7134303) SNPs and suggested a synergistic effect between the variants. These findings suggest that Dectin-2, MCP-1 and DC-SIGN polymorphisms may, at least in part, account for gender-associated differences in susceptibility to RA.
|
|
| 28. |
- Campa, Daniele, et al.
(författare)
-
A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
- 2012
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (P-trend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (P-trend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC.
|
|
| 29. |
- Campa, Daniele, et al.
(författare)
-
Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study
- 2010
-
Ingår i: BMC Gastroenterology. - 1471-230X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development. Methods: We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic. Results: We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany. Conclusion: A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (P-trend = 0.004).
|
|
| 30. |
- Carrai, Maura, et al.
(författare)
-
Association Between TAS2R38 Gene Polymorphisms and Colorectal Cancer Risk: A Case-Control Study in Two Independent Populations of Caucasian Origin
- 2011
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99-1.67; P-value = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06-1.75; P-value = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12-1.61; P-value = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin.
|
|
