| 1. |
- Fang, Fang, et al.
(författare)
-
Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer
- 2011
-
Ingår i: PLOS ONE. - San Fransisco, USA : Public Library Science. - 1932-6203. ; 6:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis.Methodology/principal findings: We examined the associations between prediagnostic plasma levels of 25(OH)vitamin D [25(OH)D] and 1,25(OH)(2) vitamin D [1,25(OH)(2)D] and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH)D. There was no association between 1,25(OH)(2)D and total mortality. Men with the lowest 25(OH)D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P(trend) = 0.006). This association was largely explained by the association between low 25(OH)D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH)D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)(2)D levels were not associated with lethal prostate cancer.Conclusions/significance: Although potential bias of less advanced disease due to more screening activity among men with high 25(OH)D levels cannot be ruled out, higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis.
|
|
| 2. |
- Meyer, Mara S., et al.
(författare)
-
Genetic variation in RNASEL associated with prostate cancer risk and progression
- 2010
-
Ingår i: Carcinogenesis. - Oxford, United Kingdom : Oxford University Press. - 0143-3334 .- 1460-2180. ; 31:9, s. 1597-603
-
Tidskriftsartikel (refereegranskat)abstract
- Variation in genes contributing to the host immune response may mediate the relationship between inflammation and prostate carcinogenesis. RNASEL at chromosome 1q25 encodes ribonuclease L, part of the interferon-mediated immune response to viral infection. We therefore investigated the association between variation in RNASEL and prostate cancer risk and progression in a study of 1286 cases and 1264 controls nested within the prospective Physicians' Health Study. Eleven single-nucleotide polymorphisms (SNPs) were selected using the web-based 'Tagger' in the HapMap CEPH panel (Utah residents of Northern and Western European Ancestry). Unconditional logistic regression models assessed the relationship between each SNP and incident advanced stage (T(3)/T(4), T(0)-T(4)/M(1) and lethal disease) and high Gleason grade (>/=7) prostate cancer. Further analyses were stratified by calendar year of diagnosis. Cox proportional hazards models examined the relationship between genotype and prostate cancer-specific survival. We also explored associations between genotype and serum inflammatory biomarkers interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha receptor 2 using linear regression. Individuals homozygous for the variant allele of rs12757998 had an increased risk of prostate cancer [AA versus GG; odds ratio (OR): 1.63, 95% confidence interval (CI): 1.18-2.25), and more specifically, high-grade tumors (OR: 1.90, 95% CI: 1.25-2.89). The same genotype was associated with increased CRP (P = 0.02) and IL-6 (P = 0.05) levels. Missense mutations R462Q and D541E were associated with an increased risk of advanced stage disease only in the pre-prostate-specific antigen era. There were no significant associations with survival. The results of this study support a link between RNASEL and prostate cancer and suggest that the association may be mediated through inflammation. These novel findings warrant replication in future studies.
|
|
| 3. |
- Shui, Irene M, et al.
(författare)
-
Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality
- 2012
-
Ingår i: The Prostate. - : Wiley-Blackwell. - 0270-4137 .- 1097-0045. ; 72:2, s. 209-216
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer.METHODS: In a large nested case-control study of prostate cancer in the Physicians' Health Study (1982-2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/T4, M1/N1(T1-T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases.RESULTS: The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases.CONCLUSIONS: Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality.
|
|
| 4. |
- Epstein, Mara M, et al.
(författare)
-
Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue
- 2012
-
Ingår i: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 23:8, s. 1359-1366
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Recent studies suggest variation in genes along the vitamin D pathway, as well as vitamin D receptor (VDR) protein levels, may be associated with prostate cancer. As serum vitamin D levels vary by season, we sought to determine whether the expression of genes on the vitamin D pathway, assessed in prostate tumor tissue, do the same.METHODS: Our study incorporates mRNA expression data from 362 men in the Swedish Watchful Waiting cohort, diagnosed between 1977 and 1999, and 106 men enrolled in the US Physicians' Health Study (PHS) diagnosed between 1983 and 2004. We also assayed for VDR protein expression among 832 men in the PHS and Health Professionals Follow-up Study cohorts. Season was characterized by date of initial tissue specimen collection categorically and by average monthly ultraviolet radiation levels. One-way analysis of variance was used to examine variation in the expression levels of six genes on the vitamin D pathway-VDR, GC, CYP27A1, CYP27B1, RXRα, CYP24A1-and VDR protein by season, adjusted for age at diagnosis and Gleason grade. Variation was also examined separately among lethal and nonlethal cases.RESULTS: Tumor expression levels of the six genes did not vary significantly by season of tissue collection. No consistent patterns emerged from subgroup analyses by lethal versus nonlethal cases.CONCLUSIONS: Unlike circulating levels of 25(OH) vitamin D, expression levels of genes on the vitamin D pathway and VDR protein did not vary overall by season of tissue collection. Epidemiological analyses of vitamin D gene expression may not be biased by seasonality.
|
|
| 5. |
- Fang, Fang, et al.
(författare)
-
Immediate risk of suicide and cardiovascular death after a prostate cancer diagnosis : cohort study in the United States
- 2010
-
Ingår i: Journal of the National Cancer Institute. - New York, USA : Elsevier. - 0027-8874 .- 1460-2105. ; 102:5, s. 307-14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Receiving a cancer diagnosis is a stressful event that may increase risks of suicide and cardiovascular death, especially soon after diagnosis.Methods: We conducted a cohort study of 342,497 patients diagnosed with prostate cancer from January 1, 1979, through December 31, 2004, in the Surveillance, Epidemiology, and End Results Program. Follow-up started from the date of prostate cancer diagnosis to the end of first 12 calendar months after diagnosis. The relative risks of suicide and cardiovascular death were calculated as standardized mortality ratios (SMRs) comparing corresponding incidences among prostate cancer patients with those of the general US male population, with adjustment for age, calendar period, and state of residence. We compared risks in the first year and months after a prostate cancer diagnosis. The analyses were further stratified by calendar period at diagnosis, tumor characteristics, and other variables.Results: During follow-up, 148 men died of suicide (mortality rate = 0.5 per 1000 person-years) and 6845 died of cardiovascular diseases (mortality rate = 21.8 per 1000 person-years). Patients with prostate cancer were at increased risk of suicide during the first year (SMR = 1.4, 95% confidence interval [CI] = 1.2 to 1.6), especially during the first 3 months (SMR = 1.9, 95% CI = 1.4 to 2.6), after diagnosis. The elevated risk was apparent in pre-prostate-specific antigen (PSA) (1979-1986) and peri-PSA (1987-1992) eras but not since PSA testing has been widespread (1993-2004). The risk of cardiovascular death was slightly elevated during the first year (SMR = 1.09, 95% CI = 1.06 to 1.12), with the highest risk in the first month (SMR = 2.05, 95% CI = 1.89 to 2.22), after diagnosis. The first-month risk was statistically significantly elevated during the entire study period, and the risk was higher for patients with metastatic tumors (SMR = 3.22, 95% CI = 2.68 to 3.84) than for those with local or regional tumors (SMR = 1.57, 95% CI = 1.42 to 1.74).Conclusion: A diagnosis of prostate cancer may increase the immediate risks of suicide and cardiovascular death.
|
|
| 6. |
- Markt, Sarah C., et al.
(författare)
-
Genetic Variation Across C-Reactive Protein and Risk of Prostate Cancer
- 2014
-
Ingår i: The Prostate. - : Wiley-Blackwell. - 0270-4137 .- 1097-0045. ; 74:10, s. 1034-1042
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Inflammation has been hypothesized to play an important etiological role in the initiation or progression of prostate cancer. Circulating levels of the systemic inflammation marker C-reactive protein (CRP) have been associated with increased risk of prostate cancer. We investigated the role of genetic variation in CRP and prostate cancer, under the hypothesis that variants may alter risk of disease.METHODS. We undertook a case-control study nested within the prospective Physicians' Health Study among 1,286 men with incident prostate cancer and 1,264 controls. Four single-nucleotide polymorphisms (SNPs) were selected to capture the common genetic variation across CRP (r(2) > 0.8). We used unconditional logistic regression to assess the association between each SNP and risk of prostate cancer. Linear regression models explored associations between each genotype and plasma CRP levels.RESULTS. None of the CRP SNPs were associated with prostate cancer overall. Individuals with one copy of the minor allele (C) in rs1800947 had an increased risk of high-grade prostate cancer (OR: 1.7; 95% CI: 1.1-2.8), and significantly lower mean CRP levels (P-value < 0.001), however, we found no significant association with lethal disease. Mean CRP levels were significantly elevated in men with one or two copies of the minor allele in rs3093075 and rs1417939, but these were unrelated to prostate cancer risk.CONCLUSION. Our findings suggest that SNPs in the CRP gene are not associated with risk of overall or lethal prostate cancer. Polymorphisms in CRP rs1800947 may be associated with higher grade disease, but our results require replication in other cohorts.
|
|
| 7. |
- Mucci, Lorelei A., et al.
(författare)
-
Circadian dysrhythm and advanced prostate cancer
- 2014
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:4
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The circadian rhythm regulates diverse biologic pathways including tumor oncogenes, metabolism, and cell proliferation. Dysregulation of the circadian rhythm arises from faulty input signals such as exposure to light at night, variability in core circadian rhythm genes, and variation in outputs that regulate circadian behavior including melatonin. There is compelling biologic rationale, but little human data, on circadian dysrhythm and advanced prostate cancer.Methods: We undertook an integrative molecular epidemiology study of circadian dysrhythm and advanced prostate cancer among men in the Icelandic AGES-Reykjavik cohort and the U.S. Health Professionals Follow-up Study, which allowed integration of questionnaire data, biorepositories, and long-term follow-up. We characterized circadian dysrhythm using complimentary approaches: information on sleep problems from questionnaires, prediagnostic melatonin (6-sulfatoxymelatonin) measured on first morning void urine samples, and genetic variation across twelve circadian clock genes. We used multivariable regression models to estimate relative risks (RR) and 95% confidence intervals (CI) of associations with advanced prostate cancer, adjusted for potential confounders.Results: Twenty percent of men reported sleep problems. Men who had trouble falling asleep (RR = 2.1; 95% CI 0.7-6.2) and staying asleep (RR=3.2, 95% CI 1.1-9.7) had an increased risk of developing advanced prostate cancer. Men with sleep problems had significantly lower melatonin levels compared to those without. Low melatonin levels were associated with a statistically significant 4-fold higher risk of advanced prostate cancer compared to those with high levels (95% CI: 1.25-10.0). Variant alleles in two SNPs in cryptochrome (CRY1), involved in generating and maintaining circadian rhythms, were significantly associated with risk of advanced prostate cancer in both cohorts, with a gene-level p-value<0.01.Conclusions: Our results suggest there are multiple nodes in the circadian rhythm that are associated with an increased risk of advanced prostate cancer. As such, there is the potential for complimentary strategies to target circadian disruption and reduce the risk of advanced prostate cancer.
|
|
| 8. |
- Sigurdardottir, Lara G., et al.
(författare)
-
Sleep disruption among older men and risk of prostate cancer
- 2013
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 22:5, s. 872-879
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Although positive associations have consistently been reported between sleep disruption and breast cancer, less is known about its potential role in prostate cancer.Methods: Within the prospective AGES-Reykjavik cohort study, we followed 2,102 men recruited in 20022006 until the end of 2009. Participants answered questions on sleep disruption. Information on the occurrence of prostate cancer was obtained through record linkages across the Icelandic Cancer Registry. We used Cox regression models with 95% confidence intervals (CI) to estimate HRs of prostate cancer by symptoms of sleep disruption.Results: During follow-up, 135 men (6.4%) were diagnosed with prostate cancer. Compared with men without sleep disruption, those with problems falling and staying asleep were at significantly increased risk of prostate cancer [HR, 1.7 (95% CI, 1.0-2.9) and 2.1 (95% CI, 1.2-3.7)], respectively, with increasing sleep disruption severity. When restricted to advanced prostate cancer (>= stage T3 or lethal disease), these associations became even stronger [HR 2.1 (95% CI, 0.7-6.2) and 3.2 (95% CI, 1.1-9.7)]. The results did not change after excluding from the analyses men who woke up during the night, indicative of nocturia, suggesting limited risk of reverse association.Conclusions: Our data suggest that certain aspects of sleep disruption may confer an increased risk of prostate cancer and call for additional, larger studies with longer follow-up times.Impact: Prostate cancer is one of the leading public health concerns in men; if confirmed in future studies, the association between sleep disruption and prostate cancer risk may open new avenues for prevention.
|
|
