Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial.

BACKGROUND: The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29,584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with "factor D," a combination of 50 microg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention. METHODS: Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models. RESULTS: Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .047) [corrected]. Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality. CONCLUSION: The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.

Chemoprevention of primary liver cancer: a randomized, double-blind trial in Linxian, China.

BACKGROUND: Primary liver cancer is a common malignancy with a dismal prognosis. New primary prevention strategies are needed to reduce mortality from this disease. We examined the effects of supplementation with four different combinations of vitamins and minerals on primary liver cancer mortality among 29450 initially healthy adults from Linxian, China. METHODS: Participants were randomly assigned to take either a vitamin-mineral combination ("factor") or a placebo daily for 5.25 years (March 1986-May 1991). Four factors (at doses one to two times the US Recommended Daily Allowance)-retinol and zinc (factor A); riboflavin and niacin (factor B); ascorbic acid and molybdenum (factor C); and beta-carotene, alpha-tocopherol, and selenium (factor D)-were tested in a partial factorial design. The study outcome was primary liver cancer death occurring from 1986 through 2001. Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of liver cancer death with and without each factor. All P values are two-sided. RESULTS: A total of 151 liver cancer deaths occurred during the analysis period. No statistically significant differences in liver cancer mortality were found comparing the presence and absence of any of the four intervention factors. However, both factor A and factor B reduced liver cancer mortality in individuals younger than 55 years at randomization (HR = 0.59, 95% CI = 0.34 to 1.00, and HR = 0.54, 95% CI = 0.31 to 0.93, respectively) but not in older individuals (HR = 1.06, 95% CI = 0.71 to 1.59, and HR = 1.12, 95% CI = 0.75 to 1.68, respectively). Factor C reduced liver cancer death, albeit with only borderline statistical significance in males (HR = 0.70, 95% CI = 0.47 to 1.02) but not in females (HR = 1.30, 95% CI = 0.72 to 2.37). Cumulative risks of liver cancer death were 6.0 per 1000 in the placebo arm, 5.4 per 1000 in the arms with two factors, and 2.4 per 1000 in the arm with all four factors. CONCLUSION: None of the factors tested reduced overall liver cancer mortality. However, three factors reduced liver cancer mortality in certain subgroups.

[A prospective study on the relationship between nutrition intervention and incidence of malignant tumors in Lin County, China].

OBJECTIVE: To analyze the tendency in the incidence of malignant tumors in nutrition-intervened population of Lin County. METHODS: Subjects who had been enrolled in the General Population Trial, Lin County Nutrition Intervention Trial were followed up and the data of malignant tumors were collected with collaboration of National Cancer Institute/National Institute of Health. Incidences of malignant tumors during and after nutrition intervention were calculated and compared. RESULTS: Esophageal cancer, cardiac cancer, and stomach cancer were constantly the three leading cancers, accounting for 84.06% and 83.74% of the malignant tumors in men and women, respectively. The incidences of lung cancer and liver cancer in men showed increasing tendencies, while similar tendencies were found in those of stomach cancer, colorectal cancer, and liver cancer in women. With the prolonging of the follow-up, the incidences of upper digestive tract cancers declined (except stomach cancer in women). CONCLUSIONS: The upper digestive tract cancers remain the leading malignant tumors, although their incidences may decline with longer-term follow-up. Prevention and control of tumors in Lin County should still be focused on the esophageal cancer, cardiac cancer, and stomach cancer, as well as lung cancer and liver cancer.

Lung cancer chemoprevention: a randomized, double-blind trial in Linxian, China.

We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years. The combinations tested in this trial were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin; factor C, ascorbic acid and molybdenum; factor D, beta-carotene, alpha-tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the study outcome. No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P values are >0.20) or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. No significant interactions were seen for age, sex, or smoking status. Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China.

Serum concentrations of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and risk of primary liver cancer.

BACKGROUND: 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) exposure has been demonstrated to cause liver tumors in laboratory rodents. DDT's persistent metabolite and environmental degradation product, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has also been associated with liver tumors in laboratory animals. Whether DDT and DDE are associated with hepatocarcinogenesis in humans is not clear. METHODS: We carried out a nested case-control study among the participants of the Nutritional Intervention Trials in Linxian, China. The case group included 168 individuals who developed liver cancer during the trials, and the control group included 385 individuals frequency-matched on age and sex who were alive and well at the end of the study. Serum concentrations of DDT and DDE were measured by gas chromatography-mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable analysis. RESULTS: In multivariable-adjusted models, the risk of developing liver cancer increased with increased serum DDT concentration (OR for quintile 1 versus quintile 5 = 3.8, 95% CI = 1.7 to 8.6, P(trend) = .0024). In contrast, there was no statistically significant association between liver cancer and serum DDE concentration. The association between high serum DDT concentration and liver cancer was stronger among individuals with DDE concentrations below the median value (odds ratio for tertile 3 versus tertile 1 = 3.55, 95% CI = 1.45 to 8.74) than those with concentrations above the median (OR = 1.70, 95% CI = 0.97 to 2.98). A calculation of crude liver cancer risk found that there would be 26 liver cancers per 100 000 persons per year in the lowest quintile of DDT exposure versus 46 liver cancers per 100 000 persons per year in the highest quintile of DDT exposure. CONCLUSIONS: DDT may be a risk factor for liver cancer, particularly among persons with lower DDE concentrations. Risk may be particularly increased among persons exposed directly to DDT (resulting in a higher ratio of DDT to DDE) or, alternatively, risk may be associated with individual ability to metabolize DDT to DDE.

Self-reported goiter is associated with a significantly increased risk of gastric noncardia adenocarcinoma in a large population-based Chinese cohort.

Iodine is concentrated by the gastric mucosa, where it may act as an antioxidant. Therefore, iodine deficiency, and its sequelae goiter, may be associated with an increased risk of gastric cancer. We examined the association between self-reported goiter and upper gastrointestinal cancer in a Chinese cohort of 29,584 adults. Using multivariate adjusted Cox models, we found goiter associated with a significantly increased risk of gastric noncardia adenocarcinoma, HR (95% CI) 2.04 (1.01, 4.11) and nonsignificantly with gastric cardia adenocarcinoma, HR (95% CI) 1.45 (0.91, 2.30). We also found a borderline, insignificant increased risk of esophageal squamous cell carcinoma, HR (95% CI) 1.37 (0.97, 1.94). Our findings are consistent with the hypothesis that iodine deficiency is associated with an increased risk of gastric cancer.

Hepatitis C virus infection, Linxian, China.

Bloodborne viruses may have spread in rural China during the past 25 years, but population-based prevalence estimates are lacking. We examined the frequency of hepatitis C virus (HCV) and HIV type 1 (HIV-1) among residents of Linxian, a rural community in Henan Province. In 2000, blood was collected from participants (> or = 55 years of age) who had enrolled in a population-based nutritional intervention trial in 1985. We randomly selected 500 participants for HCV testing and 200 participants for HIV-1 testing. For HCV, 48 (9.6%) of 500 participants were positive by enzyme immunoassay and recombinant immunoblot assay (95% confidence interval, 7.0%-12.2%), and prevalence was lowest in the most geographically isolated participants. Among the HCV-infected participants, 42 had a specimen available from 1985, of which 16 (38.1%) were positive for HCV. For HIV-1, 0/200 participants were positive. We conclude that HCV is now a common infection among older adults in Linxian, China.

Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China.

Esophageal cancer incidence and mortality rates in Linxian, China are among the highest in the world. We examined risk factors for esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), and gastric noncardia cancer (GNCC) in a population-based, prospective study of 29,584 adults who participated in the Linxian General Population Trial. All study participants completed a baseline questionnaire that included questions on demographic characteristics, personal and family history of disease, and lifestyle factors. After 15 years of follow-up, a total of 3,410 incident upper gastrointestinal cancers were identified, including 1,958 ESCC, 1,089 GCC and 363 GNCC. Cox proportional hazard models were used to estimate risks. Increased age and a positive family history of esophageal cancer (including ESCC or GCC) were significantly associated with risk at all 3 cancer sites. Additional risk factors for ESCC included being born in Linxian, increased height, cigarette smoking and pipe smoking; for GCC, male gender, consumption of moldy breads and pipe smoking; and for GNCC, male gender and cigarette smoking. Protective factors for ESCC included formal education, water piped into the home, increased consumption of meat, eggs and fresh fruits and increased BMI; for GCC, formal education, water piped into the home, increased consumption of eggs and fresh fruits and alcohol consumption; and for GNCC, increased weight and BMI. General socioeconomic status (SES) is a common denominator in many of these factors and improving SES is a promising approach for reducing the tremendous burden of upper gastrointestinal cancers in Linxian.

[Analysis of mortality rate of stomach cancer and its trend in twenty years in China].

OBJECTIVE: To analyze and predict the trend in mortality rate of stomach cancer in twenty years in China. METHODS: Stomach cancer mortality data collected from the China national survey over the period 1970s - 1990s for the cause of death were analyzed. RESULTS: The adjusted mortality rate of stomach cancer in 1990s increased by 11.0% and 6.3% for males and females, respectively. The urban mortality in 1970s was slightly higher than the rural mortality, while in 1990s the rural mortality rate was about 60% higher than the urban mortality. In 1990s, the adjusted urban mortality rate decreased by 22.2% and 26.7% for males and females, respectively. In contrast, the rural mortality rate increased by 26.4% and 22.1% for males and females, respectively. The sex ratio of stomach cancer deaths in 1990s, both in cities and rural areas, was slightly greater than that in 1970s, being more marked in the latter areas. In 1990s, the mortality rate decreased in 12 provinces, accounting for 44% in both sexes (12/27), but the decrease was more marked for females than for males except in Kiangs province. In provinces where the increased rates ranked top six positions, the magnitude of increase in rates was higher in males than in females. CONCLUSION: The overall mortality rates of stomach cancer in the past 20 years in China presented an increasing trend, despite there were upward and downward changes in 27 provinces and decrease in cities while increase in rural areas. Compared with other countries, the world-adjusted mortality rate of stomach cancer for both sexes in China ranks first. The increasing trend in stomach cancer mortality was seen in the older age groups (> 60 years) while a decreasing trend was seen in the younger age groups (30 - 59 years). Aging of the population could be an important factor responsible for the increase in mortality rates of stomach cancer in China.

Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death.

BACKGROUND: We previously reported an inverse association between prediagnostic serum selenium concentrations and the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia cancer (GCC) but not gastric noncardia cancer (GNCC) in a nested study from the Nutrition Intervention Trial in Linxian, China. OBJECTIVE: We examined the relation between baseline serum selenium and the subsequent risk of death from ESCC, GCC, GNCC, heart disease (HD), stroke, and total death over 15 y of follow-up (1986-2001). DESIGN: We measured baseline serum selenium concentrations in 1103 subjects randomly selected from a larger trial cohort. We identified 516 deaths during the 15-y follow up, including 75 from ESCC, 36 from GCC, 116 from HD, and 167 from stroke. Relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards regression models. Reported RRs estimated the change in risk conferred by a 25% increase in serum selenium relative to the population distribution. All estimates were adjusted for sex, age, smoking, drinking, and serum cholesterol. RESULTS: We found significant inverse associations between baseline serum selenium and death from ESCC (RR: 0.83; 95% CI: 0.71, 0.98) and GCC (0.75; 0.59, 0.95). Trends toward inverse associations were noted for death from HD (0.89; 0.78, 1.01; P = 0.07), but no association was noted for total death (0.96; 0.90, 1.02) or stroke (0.99; 0.88, 1.11). CONCLUSION: Population-wide selenium supplementation in the region of China with low serum selenium and high incidences of ESCC and GCC merits serious consideration.

[Changes of mortality rate for cervical cancer during 1970's and 1990's periods in China].

OBJECTIVE: To describe the distribution changes of the mortality rate for cervical cancer in China between the 1970's and 1990's and provide the scientific evidence for the prevention and control strategies for cervical cancer campaign in China between next century. METHODS: Data from two National Surveys for the Causes of Death in 1970's and 1990's in China. The crude and adjusted mortality rates for the cervical cancer and the distributions based on age and area were calculated and described. The comparison of the differences of changes between two mortality rates periods and together with its trends were shown based on the age-standardized. RESULTS: During two decades, the mortality rate for cervical cancer was 10.7 per 100,000 in 1970's which declined to 3.89 per 100,000 in 1990's, and from the 3rd ranking among all female malignant tumors to the 6th in 1990's (decreased about 63.64%). But the declination was not evenly. There have still been some high-risk areas, most located in rural countries in the mid-west of China, with rates remain unchanged and even at the highest level in the world, such as Wudu in Gansu and Yangcheng in Shanxi. A big difference was showed between rural country and city, but in both of them, the mortality rates in 1990's were significantly much lower than in 1970's (P = 0.001) at each five-year age group. And in the city, there was a much sharper increased trend in young women in 1990's. CONCLUSIONS: The mortality rate for cervical cancer campaign in China has been substantially declined during past twenty years, but it's still a major health problem for women, especially in rural China. The focus of the prevention and control for the cervical cancer in the next century should put on rural areas, especially in mid-west of China and young women in the city.