Selenium Supplementation and Lung Cancer Incidence
7
Citation
48
Reference
20
Related Paper
Citation Trend
Abstract:
Interest in the chemopreventive effects of the trace element selenium has spanned the past three decades. Of >100 studies that have investigated the effects of selenium in carcinogen-exposed animals, two-thirds have observed a reduction in tumor incidence and/or preneoplastic endpoints (G. F. Combs and S. B. Combs, The Role of Selenium in Nutrition Chapter 10, pp. 413–462. San Diego, CA: Academic Press, 1986, and B. H. Patterson and O. A. Levander, Cancer Epidemiol. Biomark. Prev., 6: 63–69, 1997). The Nutritional Prevention of Cancer Trial, a randomized clinical trial reported by Clark et al. (L. C. Clark et al. , JAMA, 276: 1957–1963, 1996), showed as a secondary end point, a statistically significant decrease in lung cancer incidence with selenium supplementation. The adjusted hazard ratio (HR) was 0.56 [95% confidence interval (CI), 0.31–1.01; P = 0.05]. These results were based on active follow-up of 1312 participants.
This reanalysis used an extended Nutritional Prevention of Cancer Trial participant follow-up through the end of the blinded clinical trial on February 1, 1996. The additional 3 years added 8 cases to the selenium-treated group and 4 cases to the placebo group, and increased follow-up to 7.9 years. The relative risk of 0.70 (95% CI, 0.40–1.21; P = 0.18) is not statistically significant. Whereas the overall adjusted HR is not significant (HR = 0.74; 95% CI, 0.44–1.24; P = 0.26), and the HR for current and former smokers was not significant, the trend is toward a reduction in risk of incident lung cancer with selenium supplementation. In a subgroup analysis there was a nominally significant HR among subjects with baseline plasma selenium in the lowest tertile (HR = 0.42; 95% CI, 0.18–0.96; P = 0.04). The analysis for the middle and highest tertiles of baseline showed HRs of 0.91 and 1.25. The current reanalysis indicates that selenium supplementation did not significantly decrease lung cancer incidence in the full population, but a significant decrease among individuals with low baseline selenium concentrations was observed.Keywords:
Cancer Prevention
Clinical endpoint
Cite
Abstract Background: Although interventional trials demonstrated that moderate-dose β-carotene supplementation increases lung cancer mortality in smokers and asbestos-exposed workers, differences in serum concentrations in absence of supplementation have not been studied in asbestos-exposed workers. Methods: A mortality analysis was performed to assess the relationship of nonsupplemented serum β-carotene to all-cause and cancer mortalities using 1981 to 1983 serum β-carotene concentration measurements from 2,646 U.S. white male insulators (mean age, 57.7 years). Multivariable-adjusted Cox proportional hazard models that included terms for age, duration of asbestos exposure, smoking, season, and region were fitted to estimate mortality HRs and 95% confidence intervals (CI) according to serum β-carotene concentrations. Results: Median follow-up was 12.8 years and 984 (33.8%) subjects died during the follow-up period, including 415 deaths from overall cancer and 219 deaths from lung cancer. The overall mortality HR for a serum β-carotene increase of 10 μg/dL was 0.97 (95% CI, 0.96–0.99). Compared with the lowest quartile, HRs were 0.90 (95% CI, 0.76–1.07) for the second (38–65 μg/dL), 0.80 (95% CI, 0.67–0.96) for the third (66–104 μg/dL), and 0.63 (95% CI, 0.51–0.77) for the highest serum β-carotene quartile (≥105 μg/dL). There was no association between serum β-carotene and overall cancer mortality (HR, 1.00; 95% CI, 0.97–1.02) or lung cancer mortality (HR, 0.99; 95% CI, 0.96–1.02). Conclusions: Higher nonsupplemented serum β-carotene concentrations were negatively associated with all-cause mortality among asbestos-exposed individuals. Impact: Serum β-carotene can be a marker of one or more determinants of reduced mortality in asbestos-exposed workers. Cancer Epidemiol Biomarkers Prev; 24(3); 555–60. ©2014 AACR.
Baseline (sea)
Cite
Citations (16)
Vitamin E and selenium play a role in antioxidant defenses and may decrease oxidant damage to tissues and thereby reduce the Rationale: risk of COPD. Prior observational epidemiologic studies support this hypothesis, but no large randomized trials have assessed supplementation with selenium, and one trial (Heart Protection Study) found no effect of combined vitamins E, C and beta-carotene on COPD hospitalizations. The effect of selenium, vitamin E or both on COPD risk was assessed in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). SELECT was a double-blind, randomized, placebo-controlled trial of 35,533 men (median age 62.4 yrs) at 427 sites in the US, Methods: Canada, and Puerto Rico testing the single or joint effects of vitamin E (400 IU/day -α-tocopherol acetate) and selenium (200 μg/d all rac selenomethionine) in a 2x2 factorial design. As of 10/23/08, the end of supplementation in SELECT, the median length of follow-up was 5.46 years (range 4.17-7.33 years). The endpoint for the current study was assessed by participant report on bi-annual medical history questionnaires of incident physician-diagnosed emphysema, COPD and/or chronic bronchitis in 32,371 eligible men [excluding men with inadequate data (2,094) or with prevalent lung disease at baseline (1,068)]. Hazard ratios [95% confidence intervals (CIs)] for COPD were 1.08 (95% CI 0.91, 1.28) for vitamin E, 1.01 (95% CI 0.85, 1.20) for Results: selenium, and 0.94 (95% CI 0.79, 1.12) for combined vitamin E and selenium, all versus placebo/placebo. Findings were unchanged in models that included participants with a baseline report of prevalent lung disease, and Kaplan-Meier curves show no separation over time in probability of event by treatment group. The cumulative incidence of COPD was 3.27% over the follow-up period, and current smokers were at increased risk compared to never smokers (HR 7.22; 95% CI 5.99, 8.72). : Selenium or vitamin E, alone or in combination, did not prevent COPD in a population of relatively healthy men. Although it is Conclusion possible that effects may have been missed due to the short duration of treatment and suboptimal endpoint ascertainment, this study is a strong test of the hypothesis that antioxidants decrease the risk of physician-diagnosed COPD. Statistical power to test for subgroup effects in smokers is limited, although such a test follows directly from the study hypothesis. A spirometry endpoint, currently being evaluated, may give further insight into these questions in a subgroup enriched with smokers.
Cancer Prevention
Cite
Citations (1)
Cite
Citations (300)
Background: It has been suggested that a low dietary intakeofantioxidantvitaminsandmineralsincreasesthe incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficialeffect.Wetestedtheefficacyofnutritionaldoses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population. Methods: The Supplementation en Vitamines et MinerauxAntioxydants(SU.VI.MAX)studyisarandomized, double-blind, placebo-controlled primary prevention trial. A total of 13017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 µg of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years. Results: Nomajordifferencesweredetectedbetweenthe groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovasculardiseaseincidence(134[2.1%]vs137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancerincidencewasfound(P=.004).Sex-stratifiedanalysisshowedaprotectiveeffectofantioxidantsinmen(relative risk, 0.69 [95% confidence interval {CI}, 0.53-0.91]) but not in women (relative risk,1.04 [95% CI, 0.851.29]). A similar trend was observed for all-cause mortality (relative risk,0.63 [95% CI, 0.42-0.93] in men vs1.03 [95% CI, 0.64-1.63] in women; P=.11 for interaction). Conclusions: After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and allcause mortality in men but not in women. Supplementationmaybeeffectiveinmenonlybecauseoftheirlower baseline status of certain antioxidants, especially of beta carotene.
Multivitamin
Cite
Citations (15)
B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk.To investigate if 1-carbon metabolism factors are associated with onset of lung cancer.The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine.Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B(2), B(6), folate [B(9)], and B(12)), methionine, and homocysteine.Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100,000 person-years among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B(6) (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. When participants were classified by median levels of serum methionine and B(6), having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR, 0.42; 95% CI, 0.27-0.65).Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer.
Cotinine
Quartile
Cite
Citations (165)
Abstract Background: Tocopherols, as the major source of vitamin E in diet in China and US, include four isoforms (α, β, γ, and δ) differentiated by the number and position of methyl groups on the chromanol ring. Tocopherols may inhibit carcinogenesis through inhibition of cell proliferation, induction of apoptosis, inhibition of angiogenesis, and enhancement of immune function. Results of past prospective studies and randomized controlled trials that evaluated the association between tocopherols intake and female lung cancer risk have been inconsistent and did not take into consideration lung cancer histology. Methods: We prospectively evaluated the association between tocopherol isoforms from diet, vitamin E supplement use, and lung cancer risk in 72,829 Chinese female nonsmokers aged 40-70 years and participating in the Shanghai Women's Health Study (SWHS). Tocopherol exposure from dietary and supplements sources were assessed through a validated food-frequency questionnaire at baseline and reassessed during follow-up. Cox proportional hazards models with time-dependent analysis were used to calculate multivariate-adjusted Hazard ratios (HRs) and 95% confidence interval (CIs) for lung cancer. All statistical tests were two sided. Results: Between January 1997 and December 2010, 481 study participants were diagnosed with lung cancer after study enrollment. Total dietary tocopherol was inversely associated with lung cancer risk among women complying with suggested dietary guidelines for adequate intake (AI) of tocopherol (14 mg/day or more: HR: 0.73; 95% CI = 0.54-0.99; compared to the lowest category) with a significant dose-response trend (P trend=0.045). Furthermore, borderline significant inverse associations were observed for combined dietary combined β and γ tocopherol (HR: 0.79; 95% CI = 0.59-1.06), and δ-tocopherols intake (HR: 0.78; 95% CI = 0.59-1.04). Additionally, there was a significant interaction effect between vitamin E or multivitamin supplements use and total dietary tocopherol intake in analysis using AI of tocopherol (P interaction = 0.018). In contrast, vitamin E supplement use was associated with a significant increase in lung cancer risk (HR: 1.39; 95% CI = 1.07-1.82). Analyses of lung cancer histology found that vitamin E supplement use was associated with increased risk of adenocarcinoma (HR: 1.79; 95% CI = 1.23-2.60). Exclusion of 45 cases diagnosed within two years of follow-up did not change the HR estimations appreciably. Conclusion: Total dietary tocopherol may be associated with lower lung cancer risk among female non-smokers, while tocopherol from vitamin supplements use was significantly associated with increased lung adenocarcinoma risk. Our results require confirmation in other prospective studies. Citation Format: Qi-Jun Wu, Yong-Bing Xiang, Gong Yang, Hong-Lan Li, Qing Lan, Yu-Tang Gao, Wei Zheng, Xiao-Ou Shu, Jay Fowke. Vitamin E intake and the lung cancer risk among female nonsmokers: A report from the Shanghai Women's Health Study. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A46.
Cancer Prevention
Cite
Citations (0)
Nested case-control study
Cite
Citations (6)
Interest in the chemopreventive effects of the trace element selenium has spanned the past three decades. Of >100 studies that have investigated the effects of selenium in carcinogen-exposed animals, two-thirds have observed a reduction in tumor incidence and/or preneoplastic endpoints (G. F. Combs and S. B. Combs, The Role of Selenium in Nutrition Chapter 10, pp. 413-462. San Diego, CA: Academic Press, 1986, and B. H. Patterson and O. A. Levander, Cancer Epidemiol. Biomark. Prev., 6: 63-69, 1997). The Nutritional Prevention of Cancer Trial, a randomized clinical trial reported by Clark et al. (L. C. Clark et al., JAMA, 276: 1957-1963, 1996), showed as a secondary end point, a statistically significant decrease in lung cancer incidence with selenium supplementation. The adjusted hazard ratio (HR) was 0.56 [95% confidence interval (CI), 0.31-1.01; P = 0.05]. These results were based on active follow-up of 1312 participants. This reanalysis used an extended Nutritional Prevention of Cancer Trial participant follow-up through the end of the blinded clinical trial on February 1, 1996. The additional 3 years added 8 cases to the selenium-treated group and 4 cases to the placebo group, and increased follow-up to 7.9 years. The relative risk of 0.70 (95% CI, 0.40-1.21; P = 0.18) is not statistically significant. Whereas the overall adjusted HR is not significant (HR = 0.74; 95% CI, 0.44-1.24; P = 0.26), and the HR for current and former smokers was not significant, the trend is toward a reduction in risk of incident lung cancer with selenium supplementation. In a subgroup analysis there was a nominally significant HR among subjects with baseline plasma selenium in the lowest tertile (HR = 0.42; 95% CI, 0.18-0.96; P = 0.04). The analysis for the middle and highest tertiles of baseline showed HRs of 0.91 and 1.25. The current reanalysis indicates that selenium supplementation did not significantly decrease lung cancer incidence in the full population, but a significant decrease among individuals with low baseline selenium concentrations was observed.
Cancer Prevention
Clinical endpoint
Cite
Citations (219)
Abstract In vitro and animal experimental studies have reported beneficial effects of selenium on colorectal cancer (CRC), yet results from epidemiological studies are inconsistent. Few of these studies have examined CRC risk among women, and none have been sufficiently large to examine risk in subgroups. This study investigated whether baseline serum selenium concentration was associated with subsequent CRC risk among postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. We included 804 CRC cases diagnosed between October 1993 and September 2005 and 804 controls matched to cases on age, enrollment date, clinical center, race/ethnicity, hysterectomy status, and prevalent condition at baseline. Baseline serum selenium concentration was measured by atomic absorption spectrometry. Multivariate logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) associated with increasing serum selenium concentrations. The corresponding median selenium concentrations in the 1st to 5th quintiles were 110.5, 123.2, 133.5, 144.8, and 162.2 µg/l (range: 81.03 - 398.70 µg/l). The selenium concentration was weakly and positively associated with the risk of CRC (ptrend = 0.08); the adjusted ORs (95% CIs) for the risk of CRC comparing the 2nd, 3rd, 4th, and 5th quintile of serum selenium concentrations with the 1st quintile were 1.14 (0.83-1.58), 1.16 (0.84-1.60), 1.36 (0.99-1.87) and 1.27 (0.92-1.76). The trend was somewhat stronger for past and current smokers [OR (95% CI) for the 5th vs. 1st quintile = 1.38 (0.89-2.13), ptrend = 0.13] than never smokers [OR (95% CI) for the 5th vs. 1st quintile = 1.16 (0.72-1.87), ptrend = 0.48]. However, the difference was not statistically significant (pinteraction = 0.53). Findings from this large study with relatively high serum selenium concentrations suggest no beneficial effect of selenium on colorectal cancer among women, which is consistent with results of previous smaller observational studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4825.
Women's Health Initiative
Cite
Citations (0)