Nutrition Intervention Trials in Linxian, China: Supplementation With Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population

Blot, William J.; Li, Jun Yao; Taylor, Philip R.; Guo, Wenyu; Dawsey, Sanford M.; Wang, Guoqing; Yang, Chung S.; Zheng, Su Fang; Gail, Mitchell H.; Li, Guangyi; Yu, Yu; Liu, Buo qi; Tangrea, Joseph A.; Sun, Yu hai; Liu, Fusheng; Fraumeni, Joseph F.; Zhang, You Hui; Li, Bing

doi:10.1093/jnci/85.18.1483

Cited by 1,576 publications

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“…We found that prediagnostic EBV seropositivity was not positively associated with gastric cancer in this population and rather may be associated with decreased risk, especially for gastric cardia cancer which, unusually, is more common than non-cardia gastric cancer in Linxian (Blot et al, 1993). High baseline EBNA titres were also associated with decreased risk of death after diagnosis among gastric cardia cancer cases.…”

Section: Discussionmentioning

confidence: 61%

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Epstein–Barr virus serology and gastric cancer incidence and survival

Koshiol

Qiao

et al. 2007

Br J Cancer

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Among 185 cases of gastric cancer and 200 controls in Linxian, China, Epstein -Barr virus (EBV) seropositivity was not associated with increased risk of gastric cancer. High EBV nuclear antigen titres were associated with longer survival in cardia cancer cases, possibly due to chance. (Young and Rickinson, 2004), leading to speculation that it may also cause gastric cancer.Previous studies relating EBV to gastric cancer have primarily been tumour-based. The only previous study of prediagnostic EBV serology and gastric cancer incidence (Levine et al, 1995) found generally elevated odds ratios (ORs) for EBV seropositivity and gastric cancer, but included only 46 cases. No previous study has evaluated prediagnostic EBV serology and gastric cancer survival.We prospectively evaluated the associations between baseline EBV serology in relation to (1) subsequent gastric cancer and (2) survival among gastric cancer patients in the Linxian General Population Nutrition Intervention Trial (NIT) cohort in China. MATERIALS AND METHODSThe NIT was a cancer chemoprevention trial in Linxian, China, conducted from March 1986 through May 1991, that enrolled 29 584 participants (Blot et al, 1993). Follow-up for additional survival is available through May 2001 (Tran et al, 2005). We analysed the relation of baseline EBV seropositivity to gastric cancer incidence in a nested case -control study of cardia cancer cases (N ¼ 102, a random sample of the 435 cases that arose during the trial period), non-cardia cancer cases (N ¼ 83), and randomly selected controls (N ¼ 200). Case and control selection methods have been described elsewhere (Mark et al, 2000). We also analysed the association between EBV seropositivity and survival among gastric cancer cases.We tested for IgA antibodies against the EBV viral capsid antigen (VCA IgA) and the diffuse early antigen (EA-D IgA), and for IgG antibodies against the EBV viral capsid antigen (VCA IgG), diffuse early antigen (EA-D IgG), restricted early antigen (EA-R IgG), and EBV nuclear antigen complex (EBNA) using immunofluorescence assays, as previously described (Levine et al, 1995). EA-D IgA was not detectable. EBV VCA IgA, EA-D IgG, and EA-R IgG antibodies were detected in o15% of cases and controls and so were categorised as positive or negative. EBV VCA IgG and EBNA antibodies, which were detectable in all subjects, were classified as high if above the median category of antibody titres in controls and low otherwise. VCA IgG antibody titres were also analysed ordinally.Unconditional logistic regression was used to calculate ORs and 95% confidence intervals (CIs) for prediagnostic EBV serostatus and gastric cancer, controlling for age and gender. Other potential confounders (e.g., smoking, alcohol, Helicobacter pylori) were considered but did not affect the estimate for VCA IgG. KaplanMeier curves and age-and gender-adjusted Cox models were used to evaluate gastric cancer survival by baseline VCA IgG and EBNA. RESULTSCases tended to be older than controls and were more likely to be males, sm...

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Section: Discussionmentioning

confidence: 61%

“…The NIT was a cancer chemoprevention trial in Linxian, China, conducted from March 1986 through May 1991, that enrolled 29 584 participants (Blot et al, 1993). Follow-up for additional survival is available through May 2001 (Tran et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

Epstein–Barr virus serology and gastric cancer incidence and survival

Koshiol

Qiao

et al. 2007

Br J Cancer

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“…However, most of published randomized placebo-controlled primary prevention trials have not been able to demonstrate these potential beneficial effects (Blot et al, 1993; The AlphaTocopherol, Beta Carotene Cancer Prevention Study Group, 1994;Hennekens et al, 1996;Omenn et al, 1996;Lee et al, 1999;Hercberg et al, 2004), and two of the larger ones (The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group, 1994;Omenn et al, 1996) even suggested harmful effects. Only two primary prevention trials performed in China and in France (Blot et al, 1993;Hercberg et al, 2004) observed a reduction of the incidence of cancers, but no effect on cardiovascular events. The seemingly contradictory results between the observational studies and the randomized trials could be explained by the fact that the doses used in clinical trials were much higher than the highest levels achieved by usual dietary intake, which have been found to be associated with the lowest risk of cancer and CVD in observational studies.…”

Section: Introductionmentioning

confidence: 99%

“…The seemingly contradictory results between the observational studies and the randomized trials could be explained by the fact that the doses used in clinical trials were much higher than the highest levels achieved by usual dietary intake, which have been found to be associated with the lowest risk of cancer and CVD in observational studies. In fact, the two trials that observed a beneficial effect on total mortality and cancer incidence used nonpharmacological doses of a combination of several vitamins and minerals and found an effect on a population with very low baseline micronutrient status (such as the Chinese trial (Blot et al, 1993)) or, in the French SU.VI.MAX study (Hercberg et al, 2004), only in men who had a lower preradomization antioxidant status (for bcarotene and vitamin C) than women. In the SU.VI.MAX study, the risk of cancer was higher in men, and the effect of the combined antioxidant supplementation was greater among those with low baseline concentrations of serum vitamin C or vitamin E. This raises a special interest to identify factors able to modulate the level of blood antioxidant markers.…”

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confidence: 99%

Serum concentrations of β-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population

Fe²,

et al. 2005

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Objective: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of b-carotene, a-tocopherol, vitamin C, selenium and zinc. Methods: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. Results: Women had higher baseline serum b-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum b-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum b-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum b-carotene and higher selenium concentrations. Serum b-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary b-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum b-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. Conclusion: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients. IntroductionCigarette smoking, obesity and some dietary patterns are well-known risk factors for both cardiovascular disease and cancer (WCRF/AIC; Kromhout, 2001). Yet, in the past several years, an increasing number of basic and clinical studies have pointed to the role of the reactive metabolites of oxygen, the free radicals, in these pathological processes, and the potential protective effect of antioxidant nutrients such as bcarotene, vitamin C, vitamin E, selenium and zinc (Ames, Halliwell & Gutteridge, 1989;Diplock, 1991;Byers & Perry, 1992;Frei, 1994;Hercberg et al, 1998a).Epidemiological data from cross-sectional, case-control, and prospective studies have shown a strong relationship between the intake of foods rich in antioxidant vitamins and minerals, or the actual intake of these nutrients, and the risk of cancer and ischaemic cardiovascular diseases (CVD) (Block et al, 1992;Stampfer & Rimm, 1993;Byers & Guerrero, 1995;Kohlmeier & Hastings, 1995;Stampfer & Rimm, 1995;Hercberg et al, 1998a). However, most of published randomized placebo-controlled primary prevention trials have not been able to demonstrate these potential beneficial effects (Blot et al, 1993; The AlphaTocopherol, Beta Carotene Cancer Preventi...

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“…The Linxian study was one of the first nutritional intervention trials and revealed a decreased mortality in subjects receiving b-carotene, vitamin E and selenium, especially mortality due to cancer [9]. Supplementation for patients in nursing homes with a-tocopherol led to a significant lower incidence of respiratory tract infections, whereas no difference in all-cause mortality was observed [54].…”

Section: Intervention Studies In Apparently Healthy Personsmentioning

confidence: 99%

Adverse effects of vitamin E by induction of drug metabolism

Brigelius‐Flohé

2007

Genes Nutr

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Observational studies with healthy persons demonstrated an inverse association of vitamin E with the risk of coronary heart disease or cancer, the outcome of large-scale clinical trials conducted to prove a benefit of vitamin E in the recurrence and/or progression of such disease, however, was disappointing. Vitamin E did not provide benefits to patients with cardiovascular diseases, cancer, diabetes or hypertension. Even harmful events and worsening of pre-existing diseases were reported, which are hard to explain. Since vitamin E is metabolized along the same routes as xenobiotics and induces drug-metabolizing enzymes in rodents, it is hypothesized that a supplementation with high dosages of vitamin E may also lead to an induction of the drug-metabolizing system in patients that depend on drug therapy. Compromising essential therapy might therefore outweigh any benefit of vitamin E in patients. It is recommended to work out at which threshold the drug-metabolizing system can be induced in humans before new trials with high dosages of vitamin E are started.

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Nutrition Intervention Trials in Linxian, China: Supplementation With Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population

Abstract: The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements.

Cited by 1,576 publications

References 0 publications

Epstein–Barr virus serology and gastric cancer incidence and survival

Epstein–Barr virus serology and gastric cancer incidence and survival

Serum concentrations of β-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population

Adverse effects of vitamin E by induction of drug metabolism

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