| 1. |
- Brendle, Annika, et al.
(författare)
-
Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer ITGB4 as prognostic marker.
- 2008
-
Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1394-1399
-
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.
|
|
| 2. |
- Brendle, Annika, et al.
(författare)
-
Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer : a Swedish prospective case-control study.
- 2009
-
Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 45:3, s. 435-442
-
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.
|
|
| 3. |
- Castro, Felipe A, et al.
(författare)
-
Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population-A candidate gene approach.
- 2009
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 125:8, s. 1851-1858
-
Tidskriftsartikel (refereegranskat)abstract
- High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle. (c) 2009 UICC.
|
|
| 4. |
- Försti, Asta, et al.
(författare)
-
Polymorphisms in the KDR and POSTN genes : association with breast cancer susceptibility and prognosis.
- 2007
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 101:1, s. 83-93
-
Tidskriftsartikel (refereegranskat)abstract
- Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke. Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting. Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke. Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.
|
|
| 5. |
- Hemminki, Kari, et al.
(författare)
-
Concordance of survival in family members with prostate cancer
- 2008
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 26:10, s. 1705-1709
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Several earlier studies have assessed survival in prostate cancer based on familial risk of this disease. As a novel concept, we posit that factors governing survival in prostate cancer are likely to be different from those governing risk of prostate cancer. To prove this, we searched for familial clustering of survival (ie, concordance of survival among family members).PATIENTS AND METHODS: We used the nationwide Swedish Family-Cancer Database to estimate hazard rates (HRs) for cause-specific and overall survival in invasive prostate cancer. HRs show the probability of death in the study group compared with the reference group. The study covered 610 sons of affected fathers with median follow-up times for survival ranging from 34 to 76 months.RESULTS: When the survival in sons was analyzed according to the fathers' length of survival, there was a concordance of prognosis; the HR was 0.62 for sons whose fathers had survived longer than 59 months, compared with sons whose fathers had survived fewer than 24 months (P for trend, .02). On a continuous scale, the sons' survival increased almost linearly with the fathers' survival time. When the analysis was reversed and HRs were derived for fathers, the concordance of good and poor survival remained.CONCLUSION: The results are consistent in showing that both good and poor survival in prostate cancer aggregate in families. Genetic factors are likely to contribute to the results, which provide the first challenging population-level evidence on heritability in prognosis of prostate cancer.
|
|
| 6. |
- Hemminki, Kari, et al.
(författare)
-
Survival in breast cancer is familial
- 2008
-
Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 110:1, s. 177-182
-
Tidskriftsartikel (refereegranskat)abstract
- Several earlier studies have assessed survival in breast cancer based on familial risk of this disease. The results have been conflicting and suggest that the risk and prognostic factors of cancer are largely distinct. As a novel concept, we searched for familial clustering of survival, i.e., concordance of survival among family members. We used the nation-wide Swedish Family-Cancer Database to estimate hazard ratios (HRs) for cause-specific and overall survival in invasive breast cancer. HR shows the probability of death in the study group compared the reference group. The study covered 1277 mother-daughter pairs with familial breast cancer. Their median follow-up times for survival ranged from 96 to 122 months. When the survival in daughters was analyzed according to the mothers' length of survival, there was a concordance of prognosis. The HR was 0.65 in daughters whose mothers had survived > or = 120 months compared to daughters whose mothers had survived less than 36 months (P-value for trend 0.02). When the analysis was reversed and HRs were derived for mothers, the results were essentially similar (P-value for trend 0.02). The survival did not differ between patients with familial or sporadic breast cancer. The results are consistent in showing that both good and poor survival in breast cancer aggregates in families, which is a novel population-level finding for any cancer. The consistency of the results suggests that the prognosis in breast cancer is in part heritable which is likely to be explained by yet unknown genetic mechanisms.
|
|
| 7. |
- Ji, Jianguang, et al.
(författare)
-
Survival in bladder and renal cell cancers is familial
- 2008
-
Ingår i: Journal of the American Society of Nephrology. - : American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 19:5, s. 985-991
-
Tidskriftsartikel (refereegranskat)abstract
- Having family members with cancer has been associated with increased risk for bladder and renal cell cancers, but its association with survival has not been examined. This study was an analysis of the nationwide Swedish Family-Cancer Database and revealed that survival for bladder and renal cell cancers was similar whether the cancer was familial or sporadic; however, when survival in offspring was analyzed according to the affected parents' length of survival, prognosis was concordant. Cox proportional hazard regression models revealed that for bladder cancer, the risk for death among offspring whose parents survived > or =5 yr was approximately one third that of offspring whose parents survived <5 yr, after adjustment for gender, age at diagnosis, time period of diagnosis, socioeconomic status, and geographic region (adjusted hazard ratio 0.34; 95% confidence interval 0.15 to 0.80, for overall mortality). A risk of similar magnitude was found for renal cell cancer (adjusted hazard ratio 0.38; 95% confidence interval 0.16 to 0.87, for overall mortality). These population-level findings suggest heritability of prognosis for bladder and renal cell cancers. Genetic factors likely contribute to the mechanism underlying this observation.
|
|
| 8. |
- Ji, Jianguang, et al.
(författare)
-
Survival in Familial Pancreatic Cancer
- 2008
-
Ingår i: Pancreatology (Print). - : S. Karger. - 1424-3903 .- 1424-3911. ; 8:3, s. 252-256
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Family history has been reported to be associated with an increased risk of pancreatic cancer. However, its possible influence on pancreatic cancer survival has rarely been studied, probably because of the rareness of cases in the same family.METHODS: We used the nationwide Swedish Family-Cancer Database to examine the survival differences between familial and sporadic pancreatic cancers. Hazard ratios (HRs) for cause-specific and overall survival in pancreatic cancer were examined. HRs show the probability of death in the study group compared to the reference group.RESULTS: A total of 75 familial pancreatic cancers were noted. HRs were significantly higher among offspring with an affected parent compared to those without an affected parent; for cause-specific and overall survival, the HRs were 1.44 and 1.37, respectively. Reversing the analysis and deriving HRs for parents (offspring as probands) showed that familial pancreatic cancer had a worse prognosis than sporadic cases (HR 1.37 for cause-specific and 1.28 for overall survival). The HRs were close to unity among spouses with concordant pancreatic cancer.CONCLUSION: The data show that survival in familial pancreatic cancer is worse than that in sporadic disease, which could be explained by genetic factors, if other confounding factors can be excluded. and IAP.
|
|
| 9. |
- Ji, Jianguang, et al.
(författare)
-
Survival in non-Hodgkin's lymphoma by histology and family history.
- 2009
-
Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 1432-1335 .- 0171-5216. ; 135, s. 1711-1716
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Although survival has been studied for various subtypes of non-Hodgkin's lymphoma (NHL), there have been few comprehensive studies to quantify the prognosis, including all specific histologies. The effect of family history on survival in NHL has not been examined. METHODS: We used the Swedish Family-Cancer Database to estimate hazard ratios in NHL by histology and family history. RESULTS: Using diffuse centroblastic lymphoma as reference (HR 1.0), patients with Waldenström's macroglobulinemia and hairy-cell leukemia had the best survival. Survival advantage was also noted among patients with lymphoplasmacytic lymphoma and different kinds of follicular lymphomas. For T-cell lymphoma, mycosis fungoides showed a favorable prognosis. As for survival by family history, a total of 98 familial cases were noted in our Database with a similar prognosis compared to sporadic cases in both parental and offspring generations. A non-significant familial concordance of either good or poor survival was noted among family members when probands' prognosis was stratified by survival time. CONCLUSIONS: Our results provide quantitative prognosis data for patients with NHL according to specific histologies. Patients with a familial NHL had a similar prognosis compared to patients with sporadic disease. The data suggest familial concordance in either good or poor survival among family members.
|
|
| 10. |
- Ji, Jianguang, et al.
(författare)
-
Survival in ovarian cancer patients by histology and family history
- 2008
-
Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 47:6, s. 1133-1139
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Earlier studies suggest that histology has no prognostic significance in patients with invasive ovarian tumors. Studies about the effect of family history on survival have given conflicting results, which we try to clarify in this study. As an additional question, we examined whether family members share survival experience.METHODS: We used the nation-wide Swedish Family-Cancer Database to estimate hazard ratios (HRs) for cause-specific and overall survival in ovarian cancer patients by histology and family history. HRs show the probability of death in the study group compared to the reference group.RESULTS: A total of 6,049 ovarian cancer patients with specific histologies were retrieved from our Database from years 1993 to 1999. Compared to women with epithelial ovarian cancer, women with borderline epithelial tumors had the best survival (HR 0.02 and 0.14 for cause-specific and overall survival). Good survival was also noted for patients with sex cord-stromal tumors and germ cell tumors. Among specific subtypes of epithelial ovarian cancers, good survival was noted for women with clear cell and endometrioid carcinomas and mucinous cystadenocarcinoma. The study covered 80 mother-daughter pairs with a family history. Patients with a family history had a poorer survival than sporadic cases in both maternal and offspring generations. When the survival was analyzed according to the probands' length of survival, there was a non-significant concordance of prognosis.CONCLUSION: Our data showed that histology and family history are prognostic factors for ovarian tumors. Patients with a family history had a more aggressive course than the sporadic cases.
|
|
