There have been a number of epidemiological studies in the U.S. and throughout the world on the relationship between selenium and cancer. Shamberger and Frost15 reported that the selenium status of humans might be inversely related to the risk of some kinds of cancer. Two years later,16 more extensive studies indicated that the mortality due to lymphomas and cancers of the gastrointestinal tract, peritoneum, lung, and breast were lower for men and women residing in areas of the U.S. that have high concentrations of selenium in forage crops than those residing in areas with low selenium content in the forages. Those studies were supported by a later analysis of colorectal cancer mortality using the same forage data.17 A 27-country comparison revealed that total cancer mortality rate and age-corrected mortality due to leukemia and cancers of the colon, rectum, breast, ovary, and lung varied inversely with estimated per capita selenium intake.18 Similar results were also reported in China, a country where selenium intakes range from deficient to toxic levels.19
Lower selenium levels were found in serum collected from American subjects 1 to 5 years prior to diagnosis of cancer as compared to those who remained cancer free during this time.20 This association was strongest for gastrointestinal and prostatic cancers. Evidence that low serum selenium is a prediagnostic indicator of higher cancer risk was subsequently shown in studies conducted in Finland21 and Japan.22 In further case-control studies, low serum or plasma selenium were found to be associated with increased risk of thyroid cancer,23 malignant oral cavity lesions,24 prostate cancer,25 esophageal and gastric cancers,26 cervical cancer mortality rates,27 and colorectal adenomas.28 A decade-long prospective study of selenium status and cancer incidences indicated that initial plasma selenium concentration was inversely related to subsequent risks of both nonmelanoma skin cancer and colonic adenomatous polyps.29 Patients with plasma selenium levels less than 128 ng/ml (the average normal value) were four times more likely to have one or more adenomatous polyps.
An 8-year retrospective case control study in Maryland revealed no significant association of serum selenium level and cancer risk at sites other than the bladder,30 but those with low plasma selenium levels had a twofold greater risk of bladder cancer than those with high plasma selenium. In a study with Dutch patients the mean selenium levels were significantly less than that of controls in men, but no differences were found in plasma selenium levels between healthy control women and those with cancer.31 No significant associations in three other studies were found between serum selenium concentration and risk of total cancers32 or cancers of the lungs, stomach, or rectum.33 34 In other work, significant increases of urinary selenium excretion were found in Mexican women with cervical uterine cancer as compared to controls.35 Selenium was beneficial as a supportive element in chemotherapy in women with ovarian cancer.36 In other research there appeared to be a relationship between the loss of hMLHl and improved survival in advanced ovarian cancer.37 Additional work needs to be conducted on the relationship of DNA mismatch repair and ovarian cancer.
Toenail selenium appears to be a useful biomarker of long-term exposure to this element.38 Five studies indicated that low toenail selenium values were associated with higher risks of developing cancers of the lung,39 stomach,40 breast,41 and prostate.42 43 In contrast, five other studies showed no significant difference between cancer cases and controls.44-48 It has been suggested that the reason for those not showing a relationship is because the selenium intakes of most of the subjects tested were below that necessary for protection.49 Obviously, these results indicate that many factors must be taken into consideration when evaluating plasma and toenail selenium concentrations in relation to cancer incidence.
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