Selenium for preventing cancer.

BACKGROUND: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. OBJECTIVES: To gather and present evidence needed to address two research questions:1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. SEARCH METHODS: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. DATA COLLECTION AND ANALYSIS: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. MAIN RESULTS: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk.Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed.In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individuals with low blood selenium levels could reduce their risk of cancer (particularly prostate cancer) by increasing selenium intake - has not been confirmed. As RCT participants have been overwhelmingly male (88%), we could not assess the potential influence of sex or gender.We included 15 additional observational cohort studies (70 in total; over 2,360,000 participants). We found that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7 studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to 0.97; 7 studies, 183,863 participants) were associated with the highest category of selenium exposure compared with the lowest. Cancer incidence was lower in men (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95% CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site-specific cancers for stomach, colorectal, lung, breast, bladder, and prostate cancers. However, these studies have major weaknesses due to study design, exposure misclassification, and potential unmeasured confounding due to lifestyle or nutritional factors covarying with selenium exposure beyond those taken into account in multi-variable analyses. In addition, no evidence of a dose-response relation between selenium status and cancer risk emerged. Certainty of evidence was very low for each outcome. Some studies suggested that genetic factors might modify the relation between selenium and cancer risk - an issue that merits further investigation. AUTHORS' CONCLUSIONS: Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies.Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding.Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.

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.

Online information on complementary and alternative medicine for cancer patients: evidence-based recommendations.

BACKGROUND: Many cancer patients use complementary and alternative medicine (CAM). Most websites offering online information on CAM are not helpful for them. METHODS: We extracted decisive elements for online information on CAM by analyzing the literature on the information needs of cancer patients and on counseling cancer patients on CAM. RESULTS: Key issues for online information on CAM are the qualification of the authors, transparency and accountability of the information, description of the aims, a scientific approach, description of treatment alternatives, support for the patient-physician relationship, individualized information, a summary of the information, disclosure of funding, and the privacy policy. CONCLUSIONS: The communicative challenge will be to convey information without destroying hope and motivation. We suggest that CAM topics should be integrated into broader information provided on cancer (etiology, conventional treatment). By also providing information for physicians, such a website could promote shared decision-making. Online information will gain the status of independent expert knowledge if provided by a well-known scientific organization as, e.g., a national cancer society.

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.

The health of lesbian, gay, bisexual, transgender and intersex people.

Sex, gender and sexual orientation are diverse, as are the ways of living associated with them. The extent to which people can live a free and self-determined life according to their own body, gender, sexuality and way of life influences their social resources, opportunities for participation and discrimination and has an influence on their life situation and health. A narrative review of lesbian, gay, bisexual, transgender and intersex (LGBTI) health was conducted including international and German reviews, meta-analyses and population-based studies. The focus of this article is the legal, social and medical recognition as well as health status of LGBTI people in Germany. While the legal framework in Germany for homosexual and bisexual people has gradually improved, many civil society stakeholders have pointed to major deficits in the medical and legal recognition of transgender and intersex people. In addition, scientific findings frequently have not yet found its way into medical practice to an adequate extent. Available data on LGBTI health indicate a need for action in the areas of mental health and health care provision. However, due to a lack of comprehensive data, conclusions cannot be drawn on the general health situation and health resources of LGBTI people. For the concrete planning and implementation of measures as well as the differentiated portrayal of the situation in Germany, the databases must be expanded, not least via population-representative surveys.

Online survey of cancer patients on complementary and alternative medicine.

INTRODUCTION: Complementary and alternative medicine (CAM) is often used by cancer patients, yet, communication with the oncologist is poor. The objective of our study was to gather information on patients' usage of CAM, source of information, and aims, in order to derive strategies to improve the communication between physicians and patients on this topic. MATERIALS AND METHODS: An online survey was conducted by linking a standardized questionnaire to the largest internet portal for cancer patients in Germany. The questionnaire addresses CAM usage, disclosure to physicians, source of information, objectives for using CAM, and perceived reasons for cancer. RESULTS: Of 170 participants, 77% were currently using CAM. Disclosure to a physician was rather high with 63% having informed their oncologist. Asked whether the oncologist took time to discuss CAM, 74% answered 'no'. Most frequently used are biologically based therapies, relaxation techniques, prayer, and meditation. Most patients want to reduce side effects, boost their immune system, and get active. Almost half the participants had positive experiences with some type of CAM before they fell ill. CONCLUSION: Understanding patients' concepts of the etiology of cancer and accepting their goals for using CAM may help oncologists communicate with their patients and guide them to a safe use of CAM.

Survey of German non-medical practitioners regarding complementary and alternative medicine in oncology.

BACKGROUND: In total, 40-70% of cancer patients use complementary or alternative medicine (CAM). Many of them ask for advice from non-medical practitioners (NMPs). Our aim was to investigate the attitude of NMPs regarding their treatments for cancer patients. METHODS: A survey was performed on members of NMP associations, using an online questionnaire on diagnosis and treatment, goals for using CAM, communication with the oncologist, and sources of information. RESULTS: Of the 1,500 members of the NMP associations, 299 took part. The treatments were found to be heterogeneous. Homeopathy is used by 45% of the NMPs; 10% believe it to be a treatment directly against cancer. Herbal therapy, vitamins, orthomolecular medicine, ordinal therapy, mistletoe preparations, acupuncture, and cancer diets are used by more than 10% of the NMPs. None of the treatments is discussed with the respective physician on a regular basis. CONCLUSIONS: Many therapies provided by NMPs are biologically based and therefore may interfere with conventional cancer therapy. Thus, patients are at risk of interactions, especially as most NMPs do not adjust their therapies to those of the oncologist. Moreover, risks may arise from these CAM methods as NMPs partly believe them to be useful anticancer treatments. This may lead to the delay or even omission of effective therapies.

How many cancer patients use complementary and alternative medicine: a systematic review and metaanalysis.

BACKGROUND: No comprehensive systematic review has been published since 1998 about the frequency with which cancer patients use complementary and alternative medicine (CAM). METHODS: MEDLINE, AMED, and Embase databases were searched for surveys published until January 2009. Surveys conducted in Australia, Canada, Europe, New Zealand, and the United States with at least 100 adult cancer patients were included. Detailed information on methods and results was independently extracted by 2 reviewers. Methodological quality was assessed using a criteria list developed according to the STROBE guideline. Exploratory random effects metaanalysis and metaregression were applied. RESULTS: Studies from 18 countries (152; >65 000 cancer patients) were included. Heterogeneity of CAM use was high and to some extent explained by differences in survey methods. The combined prevalence for "current use" of CAM across all studies was 40%. The highest was in the United States and the lowest in Italy and the Netherlands. Metaanalysis suggested an increase in CAM use from an estimated 25% in the 1970s and 1980s to more than 32% in the 1990s and to 49% after 2000. CONCLUSIONS: The overall prevalence of CAM use found was lower than often claimed. However, there was some evidence that the use has increased considerably over the past years. Therefore, the health care systems ought to implement clear strategies of how to deal with this. To improve the validity and reporting of future surveys, the authors suggest criteria for methodological quality that should be fulfilled and reporting standards that should be required.

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.