Selenium for preventing cancer.

BACKGROUND: This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS: We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA: We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS: For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS: We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. AUTHORS' CONCLUSIONS: Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Selenium for preventing cancer

BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVE: Two research questions were addressed in this review: What is the evidence for: 1. an aetiological relationship between selenium exposure and cancer risk in women and men?; 2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched electronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio, OR, 0.69; 95 percent confidence interval, CI, 0.53 to 0.91) and mortality (OR 0.55, 95 percent CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95 percent CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95 percent CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics. The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification. The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.

Selenium for preventing cancer.

BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for1. an aetiological relationship between selenium exposure and cancer risk in women and men?2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched electronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio (OR) 0.69 (95% confidence interval (CI) 0.53 to 0.91) and mortality (OR 0.55, 95% CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics.The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification.The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.

Founder mutations among the Dutch.

Many genetic disorders demonstrate mutations that can be traced to a founder, sometimes a person who can be identified. These founder mutations have generated considerable interest, because they facilitate studies of prevalence and penetrance and can be used to quantify the degree of homogeneity within a population. This paper reports on founder mutations among the Dutch and relates their occurrence to the history and demography of the Netherlands. International migration, regional and religious endogamy, and rapid population growth played key roles in shaping the Dutch population. In the first millenniums BC and AD, the Netherlands were invaded by Celts, Romans, Huns, and Germans. In more recent times, large numbers of Huguenots and Germans migrated into the Netherlands. Population growth within the Netherlands was slow until the 19th century, when a period of rapid population growth started. Today, the Dutch population numbers 16 million inhabitants. Several different classes of founder mutations have been identified among the Dutch. Some mutations occur among people who represent genetic isolates within this country. These include mutations for benign familial cholestasis, diabetes mellitus, type I, infantile neuronal ceroid lipofuscinosis, L-DOPA responsive dystonia, and triphalangeal thumb. Although not related to a specific isolate, other founder mutations were identified only within the Netherlands, including those predisposing for hereditary breast-ovarian cancer, familial hypercholesterolemia, frontotemporal dementia, hereditary paragangliomas, juvenile neuronal ceroid lipofuscinosis, malignant melanoma, protein C deficiency, and San Filippo disease. Many of these show a regional distribution, suggesting dissemination from a founder. Some mutations that occur among the Dutch are shared with other European populations and others have been transmitted by Dutch émigrés to their descendents in North America and South Africa. The occurrence of short chromosomal regions that have remained identical by descent has resulted in relatively limited genetic heterogeneity for many genetic conditions among the Dutch. These observations demonstrate the opportunity for gene discovery for other diseases and traits in the Netherlands.

The association between smoking, beverage consumption, diet and bladder cancer: a systematic literature review.

In this paper the association between smoking history, beverage consumption, diet and bladder cancer incidence is systematically reviewed. A rating system has been used to summarise the level of scientific evidence (i.e. convincing, probable, possible, and no evidence) and the level of association (i.e. substantially increased, (RR> or =2.5), moderately increased (1.5< or =RR<2.5), slightly increased (1.2< or =RR<1.5), no association (0.8< or =RR<1.2), slightly decreased (0.7< or =RR<0.8), moderately decreased (0.4< or =RR<0.7), and substantially decreased (RR<0.4)). There is convincing evidence that cigarette smoking status, frequency and duration substantially increase the risk of bladder cancer. However, the evidence is not clear for other forms of smoking. A small increased risk for cigar, pipe, and environmental smoking is only possible. There is possible evidence that total fluid intake is not associated with bladder cancer. Although there is convincing evidence for a positive association between alcohol consumption and bladder cancer risk in men, the risk is small and not clinically relevant. Coffee and tea consumption are probably not associated with bladder cancer. The authors conclude that total fruit consumption is probably associated with a small decrease in risk. There is probably no association between total vegetable intake, vitamin A intake, vitamin C intake and bladder cancer and a possibly moderate inverse association with vitamin E intake. Folate is possibly not associated with bladder cancer. There probably is a moderate inverse association between selenium intake and bladder cancer risk.

Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study.

Results of a randomized controlled trial have suggested a protective effect of selenium against prostate cancer. Few other prospective studies have been conducted to confirm or refute this. The association between prostate cancer and baseline toenail selenium level was evaluated in the Netherlands Cohort Study, conducted among 58,279 men, aged 55-69 years at entry. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 6.3 years of follow-up, 540 incident prostate carcinoma cases and 1,211 subcohort members with complete toenail selenium data were available for case-cohort analyses. In multivariate survival analysis, an inverse association between toenail selenium level and prostate cancer risk was observed. Incidence rate ratios in increasing selenium quintiles were 1.00 (ref), 1.05, 0.69, 0.75, and 0.69 (95% confidence interval, 0.48-0.99), respectively (P-trend=0.008). This association persisted after exclusion of cases diagnosed during early follow-up. The inverse association was more pronounced in ex-smokers than current smokers, and unclear in never-smokers. Analysis of effect modification by intake of antioxidant vitamins C, E, and the carotenoids alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin showed a strong, significant interaction with beta-cryptoxanthin, and to a lesser extent with vitamin C. These results confirm the hypothesis that higher selenium intake may reduce prostate cancer risk. Future research on optimum dose level is needed.

Benefits and risks of pharmacological smoking cessation therapies in chronic obstructive pulmonary disease.

Smoking cessation is the most effective way to reduce the risk of developing chronic obstructive pulmonary disease (COPD) or to reduce its progression. However, little is known about the efficacy and safety of different pharmacological smoking cessation therapies used for the treatment of patients with COPD who smoke. The aim of this review was to evaluate the benefits and risks of pharmacological smoking cessation therapies in COPD. We conducted an extensive computer-aided literature search which resulted in the identification of four papers that met the inclusion criteria and contributed to this review. In two studies the efficacy of nicotine polacrilex (nicotine gum) was assessed. In one study, which did not have a control group, the efficacy of nicotine nasal spray was evaluated. The fourth study, a placebo-controlled trial, evaluated the efficacy of bupropion sustained release. The results of these studies indicated that nicotine gum, nicotine nasal spray and bupropion have a good safety profile and seem to increase abstinence rates in smokers with COPD. The incidence and nature of specific adverse effects occurring in patients with COPD seem to be comparable with the adverse effects reported by healthy smokers. However, the efficacy seems to depend on the follow-up period used to define success (i.e. abstinence rates decline with longer follow-up), as well as the intensity and duration of the concomitant psychosocial intervention. This review indicates that for a continuation of the effect of pharmacological smoking cessation therapies, the combination of pharmacotherapy (to reduce craving and withdrawal) and a relapse-prevention programme, in which attention is focused on the behavioural aspects of smoking and smoking cessation, seems to increase abstinence, especially when the psychosocial intervention is prolonged for a longer period. Also, the characteristics of the smokers who are motivated to quit must be taken into account in order to increase the number of successful attempts to quit smoking and prevent relapses. We therefore recommend using a holistic approach in which the possible coexistence of multiple problems (which are known to affect the success of smoking cessation strategies) is integrated.

Prediagnostic toenail selenium and risk of bladder cancer.

The association between several cancers and selenium status has been investigated in epidemiological studies. However, few results concerning bladder cancer have been reported thus far. The association between toenail selenium status and subsequent bladder cancer incidence was investigated in a prospective cohort study among 120,852 men and women aged 55-69 years at baseline (September 1986). The cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. Follow-up for incident cancer was established by record linkage to cancer registries until December 1992. The multivariable case-cohort analysis was based on 431 bladder cancer cases and 2,459 subcohort members, for whom toenail selenium levels were available. The age-, sex- and smoking-adjusted rate ratios (95% confidence intervals) for increasing quintiles of toenail selenium were 1.00 (reference), 1.09 (0.80-1.48), 0.55 (0.38-0.79), 0.63 (0.43-0.91), and 0.67 (0.46-0.97), respectively (P-trend < 0.01). Analyses with selenium as a continuous variable supported these findings. An inverse association between toenail selenium and bladder cancer risk was most pronounced among ex-smokers (P-trend < 0.01); was similar for subjects with high versus low intakes of beta-carotene, vitamin C, and vitamin E; and was mainly confined to invasive transitional cell carcinomas of the urinary bladder, irrespective of tumor morphology. We conclude that the evidence is in favor of an inverse association between selenium and bladder cancer risk.