In 1993, van den Brandt et al. reported a 50% decreased risk of lung cancer associated with toenail selenium concentrations (p = 0.0006). (80)
In 1994, a study of Japanese med by Kabuto et al. added to the evidence that low blood levels of selenium increase the risk for lung cancer. (81) Japanese normally have significantly higher blood selenium levels across the board, so it is not surprising that the lung cancer protecting effect of selenium was observed primarily in the lowest levels of selenium in their blood. The researchers concluded that “these exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population.”
In 1996, the data from the first ten years of the previously discussed NPC Intervention Trail (1983–1993) revealed a 44% (p=0.04) decrease in lung cancer risk (95% CI = 0.31–0.76) in association with the intervention. (46) The follow-up study, a re-analysis conducted after three years of additional follow-up revealed attenuation of the hazard ratio to 0.74. (95% CI = 0.44–1.24) (also reported as (HR 0.70, 95% CI 0.40-1.21) (51) This may suggest that there was a delay in lung cancer onset that waned with time, not a total preventive effect. Even so, the extra years of quality of life from the absence of cancer would of great value to each person.
The relationship between selenium levels and risk of lung cancer may be especially complicated due to Single Nucleotide polymorphisms of the gene for selenoprotein15 (Sep15). it has been shown that the genetic polymorphism of Sep15, resulting in different response of the protein to Se, is associated with the risk of breast and head and neck cancers The analysis of the joint effect of Sep15 polymorphism and selenium status for lung cancer development revealed that lung cancer risk differed between the Se15 genotype groups. An increasing selenium concentration was associated with a decreased risk in all individuals. (82)
Also in 1998, Knekt et al. published their “nested” case-control study of 9,000 Finns. They found that there was a significantly higher relative risk of lung cancer between the lowest and highest tertiles of serum selenium. Persons with blood selenium levels in the highest third had 60% less risk of lung cancers (42)
In 2004, a meta analysis by Zhuo et al. of 16 studies found a significantly decreased risk (RR=0.74) of lung cancer with increased selenium intake or status. (83)
In the 2004 SU.VI.MAX Intervention Trial report, lung cancer was not delineated per se, but was included in the broader category of “respiratory tract cancers.” (55) In men, the incidence of respiratory cancers was reduced from the 88 per 100,000 person years for the control group to only 37 per 100,000 person years for the supplemented group. In women, who had better diets and may have a higher expression of selenoproteins due to estrogenic effects, the incidence of respiratory tract cancers was reduced from 21 per 100,000 person years in the control group to only 12 per 100,000 person years in the supplemented group.
In 2007, Mahabir et al. reported that dietary selenium intake was inversely associated with risk for lung cancer in men (p = 0.04). (84)
Plasmatic selenium levels in the same patients were assayed in order to highlight the role played by free radicals in lung cancer. The role of selenium on the genesis of lung cancer is well known. Thirty-seven male patients with lung adenocarcinoma or squamous carcinoma were tested. The control group included thirty-nine healthy male subjects. A significant decrease in selenium plasma levels in the cancer patients (p=0.005) was also observed. The data suggest that histamine and selenium are two factors involved in the pathogenesis of lung cancer, which could be used in protective and therapeutic strategies. (85)
The National Cancer Institute is also sponsoring the Chemoprevention Study of Selenium for Non-Small Cell Lung Cancer. In this study, researchers are investigating the ability of selenium to prevent the development of secondary lung tumors in patients with surgically removed, early-stage NSCLC.
"Selenium may help prevent cancer through a number of different mechanisms," said Dr. Karp. "It is an essential component of the antioxidant enzyme glutathione peroxidase, which protects tissue from oxidative damage and may help stimulate apoptosis (cell death). Selenium may also play an anti-inflammatory role by blocking the 5-lipoxygenase pathway." (86)
This extensive credible evidence establishes the basis for the qualified claim that selenium is protective against lung cancer.