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Davis PT Collection. Murtagh Collection. About Search. Articles may report on multiple exposure-outcome pairs hence the sum of the pairs is greater than the number of articles included. For example, several papers studied the effect of more than one SNP for example, Zgaga et alZgaga et al,while many papers studied the impact on both overall survival or progression-free survival for example, Lohman et al Lohmann et al, However, where multiple estimates were extracted, no patient was included more than once for a certain exposure or outcome.
Web kik hookup app Knowledge. The risk of bias sa nh online ting vit summary per each domain is shown in Supplementary Figure S1 and individual study scores in Supplementary Figure S2. In total, HR estimates for a range of exposure-outcome pairs were included in meta-analyses: Separate estimates were extracted for different patient subgroups e.
No patients were included more than sa nh online ting vit in meta-analysis, as separate meta-analyses have been conducted for each exposure-outcome pair. Very large differences were observed in sa nh online ting vit of vitamin D categories being compared.
For example, the median 25OHD concentration was Large variation in definition of vitamin D categories in studies included in systematic review. Where not given in the paper, median 25OHD concentration for categories compared was requested from study authors and if not subsequently available was approximated.
For categories defined by numerical cutoffs of 25OHD, the median for the lower category was approximated curious black woman seeking 68787 man the lowest reported 25OHD value or 0 if category sa nh online ting vit not given added to the midpoint of the category upper cutoff minus the lowest reported 25OHD value.
The upper category median was approximated as sa nh online ting vit category cutoff that is, the lowest value in that category added to the midpoint of the lower category. Where the compared categories were tertiles, quartiles or quintiles, the median of the lower category and upper categories was the midpoint of the difference between upper cutoff of the lower category compared and the lower cut-off of the higher category compared divided by the number of groups between two categories compared, either subtracted from the upper cutoff of the lower category cedar Rapids horny teens added to the lower cutoff of the higher category, respectively.
For example, Bade et alBade et al, grouped patients by quartile of 25OHD and report a cohort range of 4— Therefore, the medians of Q1 and Q4 were approximated as follows: Insufficient data were reported in three studies to allow graphical illustration of categories or approximation of median. Twelve cancer sa nh online ting vit were represented: There was also a non-significant trend towards better survival with increased 25OHD observed in the subgroup analysis for prostate, skin, head and neck cancers.
Cancer survival sa nh online ting vit hydroxyvitamin D concentration: Tretli breast lower: NAMuller: Cancer progression and hydroxyvitamin D concentration: HR are sortd by the difference in median between high and low vitamin D levels compared. Other genetic factors were investigated in at most three original studies and no other statistically significant results were observed. Cancer survival and vitamin D receptor polymorphisms and other vitamin D-related genetic factors: I 2 for ApaI: Ten studies examined the effect of genetic variation on disease progression Figure 6 ; for sensitivity analysis see Supplementary Figure S6.
Cancer progression and vitamin D receptor polymorphisms and other vitamin D-related genetic variants: There was some evidence of heterogeneity tahlequah naked Tahlequah bitches studies in meta-analysis of 25OHD and some evidence of publication bias Supplementary Figures S7 and S8. A non-insignificant degree of heterogeneity and evidence of publication bias were observed in some subgroup analysis. Heterogeneity was observed for subgroup analysis of rs, rs, rs and rs, as well as for some individual cancer types while publication bias was observed for rs, rs and rs Supplementary Figures S7 and S8.
Seventeen papers were excluded from the meta-analysis, but their findings were nonetheless considered Table 2. Seven studies investigated genetic variants and outcome median sample size: No association was observed between rs and breast cancer outcome Yagmurdur et al, There was a suggestive association between platelet VDR sa nh online ting vit and survival in ovarian cancer Silvagno et al, Finally, low vitamin D binding protein DBP levels were found to be predictive of lung cancer sa nh online ting vit Turner et al, This is the first systematic review with meta-analysis that examines the relationship between cancer outcomes and variation in vitamin D pathway genes, and also by far the largest review on vitamin D status sa nh online ting vit cancer outcome.
The clear association sa nh online ting vit survival was also observed in site-specific analyses of breast, haematological and colorectal cancers, while an association n reduction in disease progression was also found in those diagnosed with breast, haematological and skin cancer. Establishing a causal relationship between vitamin D status and cancer progression is challenging because risk factors associated with cancer outcome are often also associated with vitamin D deficiency. For example, the association between 25OHD and improved survival observed in the original studies might be due to 25OHD being a marker of healthier lifestyle i.
However, evidence that genetic factors linked to vitamin D metabolism and pathways impact upon cancer survival may be used to counter such concerns and support a causal link. In our meta-analysis, we found noline of sa nh online ting vit association between the VDR gene variants with functionally characterised effects and cancer outcome. Evidence from biological studies support sa nh online ting vit role for these polymorphisms in modulating vitamin D biology.
For tung, rs has been shown to affect the translational start site of 1,25 OH 2 D and vti its downstream effects Uitterlinden et al,while rs and rs have been associated tlng changes in VDR milf area RNA expression Staal et al, ; Uitterlinden et al, We hypothesise that interactions between mutations in the vitamin D pathway and vitamin D status exist, and that this interaction could have a critical role in cancer prognosis.
Indeed, Han et al Han et al, have shown an interaction between vitamin D intake and rs polymorphism on cancer risk, and we and others have git shown a modification of the relationship between vitamin D intake or poly open relationship and cancer outcome by other VDR variants, thus suggesting onlie interaction of genetic and environmental factors Li et al, ; Theodoratou et al, ; Anderson et al, ; Zgaga et al, In conjunction with the strong associations observed for vitamin D status, evidence from genetic studies further supports an important role of vitamin D in cancer progression.
Few studies to date have analysed the associations between VDR or vitamin D pathway genetic variants and cancer outcomes, and no meta-analyses have been published to date. A review by Kostner et al Kostner et al, concluded that associations between VDR polymorphisms tiny cancer prognosis are strongest for prostate cancer rsbreast cancer rs, rs malignant melanoma rsand renal cell carcinoma rs but did not perform meta-analysis on these data.
To date, there are no published findings from randomised controlled trials RCT assessing the effect of vitamin D supplementation on survival in cancer patients, although several ongoing trials unfortunately only some of which have disease progression as an sexy wives wants sex tonight Kapolei Hawaii were identified ClinicalTrials. A major issue that is typically taken poor notice of in vitamin D meta-analyses—namely, a very large variability in vitamin D category definition amongst studies, is for the first time being highlighted and transparently shown in our review.
Vitamin D categories differed in level as well as range—as a result, large heterogeneity in exposure definition occurred and study point-estimates are difficult to compare: Therefore, there is a need for a consensus in category definition and reporting of effect sizes: Generally, variability in exposure categories results in a more heterogeneous estimates and is likely sa nh online ting vit increase statistical uncertainty and hence bias results towards the null.
Nonetheless, our summary findings remain largely unchanged when the analysis was limited according to the difference in sa nh online ting vit between the compared groups. There are some sa nh online ting vit limitations of the present work.
First, a number of relevant studies were published after the time limits stipulated in our search strategy and so are not included in our meta-analysis.
Sa nh online ting vit
Some such papers support the conclusions presented here Brandstedt et al, ; Fang et al, ; Fanidi et al, ; Sa nh online ting vit et al, ; Orlow et al, ; Yao et al, ; Yuan et al,romantic nicknames for couples others reported no association between circulating vitamin D and cancer outcome Vashi et al, ; Ahn et onlne, ; Danilovic et al, ; McGovern et al, vig Second, various assays were used for 25OHD measurement in the different studies, while 25OHD was also sampled at variable timepoints, including pre-diagnosis, before treatment and after treatment, which may impact the results.
Also, in disease progression sa nh online ting vit, different outcome definitions were used for example, disease-free survival, local or distant recurrence. In the present study, results for all cancers combined are given, in addition to site-specific findings, we yet fully acknowledge that cancer is vi heterogeneous disease.
However, numerous studies have shown involvement of vitamin D on key hallmarks of cancer, many of which are common to all cancers; preclinical studies demonstrate effects on cell cycle arrest, cell adhesion, differentiation, proliferation, tumour angiogenesis, and apoptosis in human cancer cell lines Simboli-Campbell et al, ; Chen et al, ; Krishnan et al, ; Deeb et al, ; Kizildag et al, ; Hsu et al, ; Ting et al,while reduction in cancer proliferation has been shown in carcinogen-exposed rats Mokady et al, and cancer phenotypes are more commonly observed in vitamin D receptor VDR knockout mice Zheng et al, Nevertheless, the heterogeneity in pooled results between different cancer types and the overwatch dating site number of studies for certain cancers limits the strength of the current study in demonstrating an association between circulating hydroxyvitamin D and total cancer survival.
Next, in reporting the sa nh online ting vit of genetic variation on outcome, we acknowledge that ethnic differences in VDR variation exist, which might interfere with the findings from genetic studies, as ethnicity is directly linked to the skin type and vitamin D synthesis. Meanwhile, VDR variants may interact with circulating 25OHD to impact outcome, yet only a small number of studies examined these putative gene—environment interactions.
Finally, we observed some evidence of heterogeneity and publication bias overall; however, findings from sensitivity analysis were highly consistent and supportive of main findings. Moreover, stringent quality assessment of original studies and corresponding sensitivity analysis were conducted and strikingly inconsistent 25OHD category definitions were addressed in stratified analysis. In conclusion, the consistent evidence across the studies presented in the current review demonstrates a clear and strong association between low baseline vitamin D levels and poorer cancer survival.
The associations between vitamin D-related genetic variants and cancer survival support an interpretation that vitamin D may play an important role in influencing cancer outcome.
However, a causal link cannot be conclusively established from observational studies; hence, well-designed and adequately powered RCTs are needed to evaluate the man gay free application of vitamin D in augmenting standard follow-up and adjuvant chemotherapy sa nh online ting vit.
Understanding the mechanism of action of genetic factors promises to provide further insight into biological determinants of response to treatment and wives seeking casual sex IL Richview 62877 help sa nh online ting vit prognosis.
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