4 stadіya Prostatakrebs

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While positive associations have consistently been reported between sleep disruption and breast cancer, less is known about its potential role in prostate cancer. Within the prospective AGES-Reykjavik cohort study, we followed 2, men recruited in — until the 4 stadіya Prostatakrebs of Participants answered questions on sleep disruption.

Information on the occurrence of prostate cancer was obtained through record-linkages across the Icelandic Cancer Registry. During follow-up, men 6. Compared to men without sleep disruption, those with problems falling and staying asleep were at significantly increased risk of prostate cancer [HR, 1.

The results did not change after excluding 4 stadіya Prostatakrebs the analyses men who woke up during the night, indicative of nocturia, suggesting limited risk of reverse association.

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. Prostate cancer is one of the leading 4 stadіya Prostatakrebs health concerns in men; if confirmed in future studies the association 4 stadіya Prostatakrebs sleep disruption and prostate cancer risk may open new avenues for prevention.

While data examining this hypothesis for prostate cancer risk among men are more sparse 4two Japanese cohort studies and two Canadian case-control studies have 4 stadіya Prostatakrebs an association between shift work and prostate cancer risk 5 — 8although a Swedish cohort study reported no association 9. One of the major behavioral consequences of night shift work is displacement of the sleep-wake cycle, which results in shift workers having difficulty falling asleep and staying asleep when they attempt to sleep during the day Short night-time sleep has been shown to be associated with an increased risk of prostate cancer in non-shift working men 11suggesting that sleep per se may be an important contributing risk factor.

Further, current sleep problems seem to be indicative of persistent sleep disruption over time We therefore examined the association between sleep disruption and prostate cancer risk in the population-based AGES-Reykjavik cohort.

We hypothesized that men with disruption of sleep would have an increased risk 4 stadіya Prostatakrebs prostate cancer as compared to men without sleep disruption. The AGES-Reykjavik study included 2, men aged 67 to 96 years who were randomly drawn from an established population-based cohort, the Reykjavik study, and recruited in — We excluded Question 5 in our analysis as it did not address sleep behaviour specifically.

We combined the four sleep questions in various ways to group symptoms consistent with problems falling asleep, problems staying asleep, or both, and the severity of each Figure 1.

Our rationale for the combination of the sleep questions was based on the 4 stadіya Prostatakrebs of different types of sleep problems.

For example, Questions 1 and 2 are indicative of difficulty falling asleep, which might occur in sleep-onset insomnia, whereas Questions 3 and 4 denote problems staying asleep, a common compliant in sleep-maintenance insomnia.

The combinations of three of 4 stadіya Prostatakrebs complaints was an attempt to assess severity of sleep complaints. While it is not possible to confirm a clinical sleep disorder in the current dataset, the combinations are based on logic consistent with known sleep disorders.

Of the 2, men in the cohort we excluded men who did not answer the questions on sleep and men who 4 stadіya Prostatakrebs been diagnosed with prostate cancer before study entry. Thus, none of the participants had been diagnosed with prostate cancer at study entry. Further, 4 men who were censored at diagnosis of other cancer, leaving 2, men to form our base population.

We collected information on several factors that could potentially confound the association between sleep disruption and prostate cancer. The men were followed through December 31, for the occurrence of prostate cancer and all-cause mortality. We did not have information on Gleason grade.

To obtain a more complete picture of advanced disease, men who died from prostate cancer were also classified as having advanced disease, regardless of the stage at diagnosis; all of the death-specific diagnoses had previously been retreived from the cancer registry Figure 2.

We present the distribution of potential covariates according to categories of sleep disruption. The covariates 4 stadіya Prostatakrebs were based on potential confounding effects or factors other than circadian disruption that may be related to sleep and prostate cancer. The second model was further adjusted 4 stadіya Prostatakrebs family history of prostate cancer, education, visit to a doctor in previous 12 months, diagnosis of benign prostate disease, BMI and diabetes mellitus; the third model additionally controlled for smoking and alcohol consumption.

As age- and multivariate-adjusted 4 stadіya Prostatakrebs were similar and power was limited in the analyses, we present age-adjusted HRs as our main results. We imputed missing values of BMI and alcohol use using the mean. For ordinal variables, we used the missing indicator method for handling missing data by creating a separate category for missing data and a new indicator variable to designate missingness.

The category with the most missing data was education with 55 missing values 2. To assess potential reverse association bias, 4 stadіya Prostatakrebs undiagnosed prostate cancer might cause sleep disturbance, we performed several sensitivity analyses.

First, we repeated our analyses after excluding cases diagnosed within two years after study entry. Second, we excluded men who reported waking up during the night Question 3 since men with nocturia related to undiagnosed prostate cancer may be more likely to wake 4 stadіya Prostatakrebs during the night, and hence report sleep disruption.

Men reporting taking medication for sleep Question 1 4 stadіya Prostatakrebs also excluded in this sensitivity analysis. Therefore, in this secondary analysis, we 4 stadіya Prostatakrebs sleep disruption to difficulties falling asleep Question 2 and early morning awakening Question 4. During the mean 5. The characteristics of the participants are presented in 4 stadіya Prostatakrebs 1according to presence or absence of sleep disruption.

Between 5. The mean age of participants at baseline was Men with and without sleep problems were similar with respect to age, education, family history of prostate cancer, smoking status, and BMI but those with sleep disruption were more likely to have visited a doctor in the previous 12 4 stadіya Prostatakrebs and 4 stadіya Prostatakrebs have been diagnosed with diabetes mellitus.

The men with problems getting to sleep and staying asleep see Figure 1 for definitions were more likely to have benign prostatic disease. Only the men with very severe sleep problems were more likely to consume more alcohol. Compared to men who did not report any sleep problems, in age-adjusted analyses, those who 4 stadіya Prostatakrebs problems falling and staying asleep Figure 1 were significantly at increased risk of prostate cancer with a hazard ratio of 1.

The 4 stadіya Prostatakrebs did not change materially after adjustment for potential confounding factors. The association was stronger for advanced prostate cancer than for overall prostate cancer for all types of sleep problems, especially for very severe sleep problems HR, 3. After excluding men who were diagnosed with prostate cancer within two years from study entry, too few advanced cases remained to conduct the 2-years lagged analyses. However, the association between sleep disruption and prostate cancer remained after excluding men with potential symptoms of nocturia men who reported waking up during the nightwith an age-adjusted HR of 2.

In this prospective cohort study we found that men with sleep disruption were at increased risk of prostate cancer, particularly advanced prostate cancer, when compared to men who did not report any sleep problems. The association between sleep disruption and prostate cancer was stronger for advanced disease than 4 stadіya Prostatakrebs overall prostate cancer. This may be a chance finding due to limited number of cases in the 4 stadіya Prostatakrebs for advanced cases.

It is also possible that underlying mechanisms of sleep disturbance, such as circadian disruption and reduced melatonin levels, affect prostate 4 stadіya Prostatakrebs progression to a greater extent than prostate cancer initiation Nonetheless, our data support the hypothesis that some aspect related to sleep disruption may confer an increased risk of prostate cancer. Most epidemiological studies to date on the effect of sleep or circadian rhythm disruption have focused on the impact of shift work on cancer risk.

Consistent with the hypotheses for sleep disruption, four studies found an increased risk of prostate cancer among night shift workers 5 — 8although one did not 9. To our knowledge the role of sleep disruption per seseparate from the impact of shift work, has 4 stadіya Prostatakrebs been assessed in one study on prostate cancer risk.

Kakizaki et al. Our data are consistent with this finding and suggest that impairment of sleep, either through reduced sleep duration or greater sleep disruption, increases the risk of prostate cancer. Limited data are indeed available on the direct 4 stadіya Prostatakrebs of melatonin on prostate cancer risk.

Shorter sleep duration and greater sleep disruption may be viewed as a proxy for increased melatonin suppression, given that individuals are likely to be exposed to light when not asleep at night.

Bartsch et al. Interestingly blind men, who may also have reduced exposure to 4 stadіya Prostatakrebs, have lower prostate cancer incidence when compared to the general population 2223similar to lower breast cancer risk in blind compared to sighted women Further work to establish causality is required, however.

Sleep disruption induced by shift work induces a number of physiological changes that have been 4 stadіya Prostatakrebs as possible mechanisms 4 stadіya Prostatakrebs the observed 4 stadіya Prostatakrebs in cancer risk. The endogenous circadian pacemaker, located in the suprachiasmatic nuclei SCN of the hypothalamus, is a major determinant of the timing, duration and structure of sleep 25 such that sleep propensity and consolidation are maximized when sleep occurs during the night.

Further, disruption of the molecular components of circadian clocks, particularly expression of the Period2 gene Per2 is thought to have tumor-suppressive properties 26 Notably, expression levels of Per2 were significantly lower in all proliferative prostate diseases compared with normal prostate tissue Also, a major consequence 4 stadіya Prostatakrebs shift work is light-induced inhibition of pineal melatonin secretion, which is acutely suppressed by the electric light required to enable night-shift work.

Melatonin is produced only during the biological night and is the biochemical correlate of darkness; light exposure during the night inhibits melatonin production The presence of melatonin has been shown to inhibit or slow down tumor growth both in vitro and in vivoincluding prostate cancer 30 — 35whereas suppression of melatonin via constant light exposure or pinealectomy increases tumor growth in 4 stadіya Prostatakrebs dose-dependent manner in experimental models Melatonin is also a potent free radical scavenger 4 stadіya Prostatakrebs and may facilitate reduction of oxidative stress implicated in prostate cancer progression The prospective design, complete follow-up and detailed information on a variety of potential confounders, constitute important strengths of our study.

Nevertheless, several potential limitations should be considered. First, our definition of sleep disruption rests on the four questions included in the AGES entry questionnaire on problem falling asleep, staying asleep, early morning awakening with difficulty falling back asleep and use of sleep medication.

These questions have not been validated against objective measures of sleep disruption. Morover, we have no information on the timing or duration of sleep, 4 stadіya Prostatakrebs can be important additonal factors when assessing sleep disruption.

Second, we had limited clinical information at diagnosis, with stage information for only two-thirds of the cases. Our analyses showed that the association was particularly strong for advanced disease, but the small number of cases with advanced disease limited our statistical power and yielded wide confidence intervals.

Third, despite inclusion of a wide variety of potential confounding factors in our models, we cannot exclude the possiblity that residual confounding unknown to us may account for these associations.

Lastly, and importantly, observation time in our study was short 5 years and the men only provided information on sleep problems during the prior few months, whereas the time from prostate cancer onset to clinical detection has been estimated to be a decade or more 38 If the carcinogenic effect of sleep disruption on tumour progression was mediated through melatonin suppression, laboratory studies suggest that the impact of reduced melatonin could be quite rapid 36although there is no parallel clinical evidence in humans.

It is also 4 stadіya Prostatakrebs that reports about current sleep problems are indicative of persistent sleep disruption over time 12 that may underlie a longer-term disease process. Nevertheless, the short observation time in our study may raise concerns of reverse association bias; for example, that men with undiagnosed prostate cancer may have symptoms such as nocturia before diagnosis that consequently lead to sleep disturbances.

Men with urinary symptoms hence sleep disruption related to prostate cancer, especially advanced cancer, often suffer from nocturia waking up during the night. To address this concern, we conducted sensitivity analyses in which we exluded men with symptoms of sleep disturbance that might be indicative of nocturia. Notably, the point estimates remained essentially unchanged, to some extent alleviating these concerns, although the number of cases were few.

These data lend support to the hypothesis that sleep disruption may affect prostate carcinogenesis. Sleep disruption and light-induced melatonin suppression represent plausible biological explanations underlying cancer risk, although prospective studies are needed to substantiate their respective roles. Large cohort studies entailing longer observation times, allowing for closer investigatons of the temporality of the association between sleep disruption and prostate cancer, will be needed to address this hypothesis further.

The authors thank Orn Olafsson and Johanna E. Torfadottir for 4 stadіya Prostatakrebs with statistical analyses and David Havelick for his work. Disclosure of Potential Conflicts of Interest. National Center for Biotechnology InformationU. Cancer Epidemiol Biomarkers Prev.