Selenium Supplementation in CHEK2 Cancer Patients
Selenium supplementation is not recommended for patients with CHEK2-related cancers, as there is no evidence of benefit and potential evidence of harm, particularly at doses exceeding 140 mcg/day. 1
Key Evidence Against Selenium Supplementation in Cancer Patients
Safety Concerns in Cancer Populations
A prospective observational trial in 4,459 men with early prostate cancer found mortality was significantly increased by a factor of 2.6 in men supplementing selenium at doses exceeding 140 mcg/day. 1
The ESPEN Guidelines on Nutrition in Cancer Patients (2017) explicitly state that single high-dose micronutrients should be avoided in cancer patients. 1
Large randomized controlled trials, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) with 35,533 participants, found no beneficial effect of selenium supplementation (200 mcg from selenomethionine) on cancer incidence or mortality. 1
Lack of Efficacy Evidence
The American College of Chest Physicians guidelines specifically recommend against selenium supplementation for cancer prevention, stating it "should not be used as a general strategy for lung cancer prevention." 1
A Cochrane systematic review of randomized controlled trials found no clear evidence that selenium supplementation reduced the risk of any cancer (RR 0.90,95% CI 0.70 to 1.17) or cancer-related mortality (RR 0.81,95% CI 0.49 to 1.32). 2
When analysis was restricted to studies with low risk of bias, selenium showed no effect on prostate cancer risk (RR 1.02,95% CI 0.90 to 1.14). 2
Specific Risks Identified
Selenium supplementation increased the risk of non-melanoma skin cancer (RR 1.44,95% CI 0.95 to 1.17) in three trials with 1,900 participants. 2
Multiple trials raised concerns about increased risk of type 2 diabetes, alopecia, and dermatitis from selenium supplements. 2
The narrow margin between safe and toxic doses of selenium makes supplementation particularly hazardous, with toxicity symptoms occurring at plasma levels ranging from 6-12 μmol/L. 1
CHEK2-Specific Considerations
No Therapeutic Benefit Established
The American College of Medical Genetics and Genomics (ACMG) 2023 guidelines explicitly state there is insufficient evidence for CHEK2 status to guide any specific targeted treatment, including nutritional interventions. 1
CHEK2-associated cancers do not display genomic features of homologous recombination repair deficiency, suggesting they may not respond to interventions targeting oxidative stress pathways. 1
Theoretical Concerns Without Clinical Support
While one research hypothesis suggested selenium might modify cancer risk in CHEK2 mutation carriers through selenoprotein pathways, this remains purely theoretical without clinical trial evidence. 3
The variability in cancer penetrance among CHEK2 carriers may be influenced by environmental factors, but selenium supplementation has not been validated as a beneficial modifier. 3
Clinical Recommendations
What to Avoid
Do not recommend selenium supplements exceeding 200 mcg/day under any circumstances. 1
Avoid high-dose selenium supplementation (>140 mcg/day) entirely in cancer patients, given the mortality risk demonstrated in prostate cancer populations. 1
Do not use selenium as a cancer prevention or treatment strategy in CHEK2 carriers. 1
Appropriate Selenium Management
If selenium deficiency is documented (plasma selenium <0.4 μmol/L or <32 mcg/L), correction may be appropriate for general health, but this should be distinguished from cancer-specific supplementation. 1
Selenium requirements for general health can be met through dietary sources including seafood, meats, and grain products. 1
In patients receiving parenteral nutrition for extended periods, selenium monitoring and supplementation may be necessary to prevent deficiency, but doses should remain conservative (60-100 mcg/day). 1
Common Pitfalls to Avoid
Do not extrapolate from observational studies showing inverse associations between selenium exposure and cancer risk—these associations do not establish causation and are subject to confounding, heterogeneity, and assessment biases. 2
Do not assume that correcting selenium deficiency will reduce cancer risk in CHEK2 carriers—the hypothesis that individuals with low baseline selenium benefit from supplementation has not been confirmed by subsequent trials. 2
Avoid recommending selenium based on its antioxidant properties, as large meta-analyses found no protective effects of antioxidants and slightly raised mortality with certain supplements. 1