A case-control study involving interviews with 1,200 patients with esophageal cancer and 1,200 population-based controls has been initiated in Linxian, a county in North Central China with perhaps the world's highest mortality rates for this tumor. Here we describe the rationale, study methods, and results of a pilot study that established the feasibility of the investigation.
The incidence of second primary cancers was investigated among 19,886 patients with prostate cancer. The analysis disclosed 594 new cancers, which was significantly less than the expected 1,176 cases (relative risk = 0.51). Deficits were observed for most sites but were only significant for cancers of the lip, lung, and gastrointestinal organs. The average age at diagnosis of prostate cancer was 72 years. It is likely that the apparent deficit in the incidence of second neoplasms resulted from less diagnostic aggressiveness in elderly patients with cancer compared with younger patients. The risk of developing a second primary cancer was also investigated in 4,290 men with testis cancer reported to the Danish Cancer Registry between 1943 and 1980. A significant 29% excess of second cancers was found (174 observed vs. 135 expected). A bimodal distribution of risk over time was found with a 67% excess seen among patients followed for 1-4 years that was mainly due to increased incidence of acute nonlymphocytic leukemia and malignant lymphomas. Among patients surviving 10 or more years, the overall excess of 32% observed was mainly due to cancers of the gastrointestinal tract and the urinary bladder. As part of the initial treatment for testis cancer, 82% of the patients received radiotherapy. Chemotherapy was rarely given before 1975 and then mostly to patients with a poor prognosis. Late effects of radiotherapy conceivably could account for some of the excess of second hematologic as well as solid neoplasms.
A 24-week pilot study of daily or weekly multiple vitamin supplementation among 852 adults in Linxian, where the rate of esophageal cancer is exceptionally high, demonstrated the feasibility of an intervention trial in this population. Compliance, when judged by pill count, was high for both frequencies of pill use. Only 2% of the subjects refused to take any pills, and, among pill takers, over 95% were reported to be taking most of their pills at the end of the study. Biochemical confirmation of high compliance was demonstrated in urine and blood tests, which showed markedly improved vitamin levels after supplementation. Results of the pilot study indicated that a system in which barefoot doctors were used in pill distribution was effective and that established field operating procedures for a full-scale intervention trial in this area were acceptable.
The risk of second primary cancer was evaluated in 29,128 patients who developed tumors of the urinary tract, including benign and malignant tumors of the renal pelvis and ureter and bladder papillomas in Denmark between 1943 and 1980. Among 9,162 persons with kidney cancer, 416 developed a second primary tumor [relative risk (RR) = 1.4]. Among 19,966 persons with bladder cancer, 1,423 developed a second primary tumor against 1,239 expected (RR = 1.1). The risk of bladder cancer was increased following kidney cancer in both men (RR = 6.3) and women (RR = 10.1), and kidney cancer was increased in both men (RR = 2.9) and women (RR = 4.5) following bladder cancer. These risks were particularly pronounced for cancers occurring in the ureter and renal pelvis. Etiologic similarities are likely explanations for these observations, which also emphasize the role of host factors and the multifocal nature of urothelial tumors. A decrease in relative risks since diagnosis of the first primary cancer was seen that may partly be attributed to a lessening of the intensity of medical surveillance with time. Among long-term survivors with kidney cancer, increased risks were observed for colon and pancreatic cancers, which may be related to treatment; approximately 25% received radiotherapy. Among bladder cancer patients, increased risks of cancers of the lung and larynx occurred, probably due to tobacco smoking. A slight elevation of prostate cancer (RR = 1.3) may be attributable to medical surveillance. Unexpected findings were the significant deficits of cancers of the stomach and rectum among patients with bladder cancer and stomach cancer among those with kidney cancer.
Fusui County in the Guangxi Autonomous Region of China is a high-risk area for hepatocellular carcinoma (HCC). In 1971-73, the average annual standardized (world population) mortality rate of HCC in Fusui was 20.09 and 111.75/100,000 person-years for females and males, respectively. Epidemiologic and pathologic studies of HCC have been conducted in Fusui since 1959. This paper describes some of the studies relating to the hepatitis B virus infection and aflatoxin contamination of foodstuffs.
Plasma levels of nutrients in 196 individuals were assayed as part of a study of the feasibility of a nutrition intervention trial in Linxian, a county in North Central China with exceptionally high rates of esophageal cancer. High-performance liquid chromatography analyses of samples collected in April 1983 showed low (relative to United States standards) base-line levels for retinol, alpha-tocopherol, and beta- and alpha-carotene. Repeat sampling in August 1983 revealed significantly increased plasma levels of retinol and alpha-tocopherol among those who had in the interim received daily supplementation with multivitamin pills containing the Recommended Dietary Allowance levels of those nutrients but not among those without supplementation. Levels of carotenes, which were not included in the pills, tended to increase regardless of supplementation, consistent with seasonal variations in availability of carotenoid-containing foods. Atomic absorption spectrophotometry analyses showed essentially normal levels of copper and zinc in plasma. Neither was affected by vitamin supplementation (the pills did not contain minerals) nor seasonal variation. The data are generally consistent with prior biochemical surveys in indicating marginal or low status of several nutrients in Linxian and in showing that supplementation with vitamins can effectively raise blood nutrient levels.
A correlation study linking age-adjusted lung cancer mortality rates with indices of air pollution was conducted as a first step in the investigation of the high rate of lung cancer in Liaoning Province. Mortality rates for this cancer during 1976-78 for males and females were elevated in the large industrial cities with metallurgical processing and machinery manufacturing industries, after smoking was taken into account. However, there was little correlation between measures of total suspended particulates and lung cancer rates across the 10 major cities of the Province. Neighborhood air pollution indices correlated significantly with local commune mortality rates within the largest city, and lung cancer rates were higher near certain point sources of industrial pollution (including a copper-zinc smelter). These findings indicate that the atmospheric pollution in this northern Chinese province may contribute to lung cancer risk and that further analytic epidemiologic study in this high-risk area is warranted for evaluation of the role of outdoor and indoor air pollutants.
A case-control study is currently under way in Beijing, People's Republic of China, involving approximately 165 patients with invasive moles or choriocarcinoma, 165 with hydatidiform moles, and 330 population controls, who were matched to the patients with invasive moles or choriocarcinoma on age and interval since last pregnancy. The interviews are focused on a number of suspected risk factors, including previous pregnancy outcomes, history of hydatidiform mole, medical factors, drug usage, family history, and diet. A brief background of the study and methods as established through a previous pilot study are given.
The risk of developing a second primary cancer was evaluated in approximately 19,000 persons with initial cancers of the lymphatic and hematopoietic system in Connecticut between 1935 and 1982. Significant excesses for all second cancers were observed among patients with leukemia (34%), Hodgkin's disease (70%), non-Hodgkin's lymphoma (25%), and multiple myeloma (24%). In general, the risk of second cancers was greater in males than in females, even for cohorts not showing an excess of surveillance-related prostate cancer. Among patients with leukemia, significant excesses of cancers of the lung, kidney/ureter, and prostate were noted; cutaneous melanoma was elevated only in males. These excesses did not persist in the small number of long-term survivors. Possible etiologic factors included tobacco smoking for lung and kidney cancers, medical surveillance artifact for prostate cancer, and immunosuppression for malignant melanoma and lung cancer. The large number and good prognoses of patients with chronic lymphocytic leukemia strongly influenced the pattern of second cancers when all leukemias were analyzed together; no evidence was found for an increased risk of second cancer in patients with acute lymphocytic leukemia. A disproportionate number of subsequent cancers, particularly those of the kidney and ureter, were diagnosed incidentally at autopsy. Patients with Hodgkin's disease displayed significant excesses of cancers of the buccal cavity and pharynx, lung, female breast, and thyroid. The latter 3 sites remained significantly elevated in long-term survivors (10 yr or more postdiagnosis), so that radiation therapy may have contributed to their development. Among persons with non-Hodgkin's lymphoma, cancers of the stomach, lung, brain, and connective tissue occurred excessively. The first 3 sites, plus cancers of the urinary bladder, remained elevated among long-term survivors. The brain cancer excess, not previously reported, may represent misclassification of central nervous system lymphoma. The risk of gastric cancer is reminiscent of similar findings in patients with both acquired and genetically determined immunodeficiency disorders. The alkylating agent, cyclophosphamide, used extensively in the treatment of non-Hodgkin's lymphoma, is known to cause bladder cancer in man.(ABSTRACT TRUNCATED AT 400 WORDS)
Variations in cancer incidence among whites in 1973-77 in 8 geographic areas of the Pacific Basin were compared. Substantial differences were found for the occurrences of lung cancer, cancer of the corpus uteri, and malignant melanoma. White women living in New Zealand and Australia had the lowest risk of developing lung cancer, whereas white men living in the western United States had the highest risk. Cancer of the corpus uteri occurred more commonly in the western United States than elsewhere in the Pacific Basin. Geographic areas located closest to the equator experienced the highest incidence of malignant melanoma. In all areas, the incidence rates of cancers of the lung and corpus uteri and malignant melanoma increased significantly between 1960-66 and 1973-77; after the mid-1970s, rates of cancer of the corpus uteri declined. The incidence of stomach cancer decreased in all areas. Although cervical cancer decreased in incidence over time for most women, it increased noticeably in young women. The incidence of breast cancer also rose during the 17-year period. In at least 1 geographic area, the observed increases in breast cancer incidence were confined to women under age 40.
Through the use of molecular methods and mathematical models, epidemiologists are contributing to the improved understanding of the mechanisms of cancer. Multistage models with their mechanistic basis have been useful in descriptions of initiator-promoter type behavior of some carcinogens as well as genetic predisposition to rare tumors and reproductive risk factors in breast cancer. The use of biochemical and molecular laboratory techniques on tissue and fluid samples should provide important information in the near future concerning the basic mechanisms of human cancer. The potential of these methods is not only to describe exposure to carcinogens but also to indicate various host factors and their relevance to the risk of cancer.
Cohort studies play an important role in the quantitation of cancer risk among occupationally exposed individuals. Properly conducted cohort studies can develop important data on the age, time, and exposure dependence of cancer risk. Such information allows identification of possible selection effects which may be present and allows generalization of risk estimates to other exposure circumstances.
The South Pacific Commission Cancer Registry has been operational since 1977, and reasonably complete cancer incidence rates are available for New Caledonia, Fiji, Micronesia, the Cook Islands, and Niue. In addition, less complete reporting is available from American Samoa, Papua New Guinea, and French Polynesia. Cancers of the lung, oral cavity, esophagus, liver, and cervix are potentially preventable but prevalent in many Pacific island countries. Unusually low rates of many cancers were observed in Fiji, the most notable being lung and colon-rectum. Thyroid cancer rates are elevated in some but not all female populations. These and other variations in cancer by site are important areas for further research.
Second primary cancers were studied in persons with rare tumors between 1943 and 1980. The risk of developing a new cancer was evaluated in 7,211 persons with cutaneous melanoma, 1,784 persons with eye cancer, 10,273 persons with tumors of the brain and nervous system, 1,935 persons with thyroid cancer, 1,542 persons with bone tumors, and 2,318 persons with malignant neoplasms of the connective tissue. All cancer patients were diagnosed in Denmark between 1943 and 1980 and survived for 2 or more months. Nonmelanoma skin cancers were excluded from the analysis, whereas tumors of the brain and nervous system included both benign and malignant neoplasms. Overall, patients with these cancers showed no greater incidence of new tumors than expected from comparisons with the general population. An excess of chronic lymphocytic leukemia was observed subsequent to all cancers derived from the neural tube, i.e., melanoma and tumors of the eye, brain, and nervous system. Bone cancer occurred excessively, although the possibility of misclassified metastases could not be eliminated. Patients with tumors of the brain and nervous system who survived for 10 or more years developed significantly more cancers of the kidney and connective tissue and melanoma than anticipated. A deficit of second cancers of the digestive system was noted after primary bone and connective tissue cancers, in contrast to an excess of second cancers of the lung and kidney. Although based on few cases, patients with bone cancer showed a large excess of eye cancer as a second primary. The association between cancers of the breast and connective tissue was found to be bidirectional. Persons with connective tissue cancer were at increased risk of developing non-Hodgkin's lymphoma. Thyroid cancer patients were at high risk of subsequent tumors of the brain and nervous tissue and non-Hodgkin's lymphoma. However, contrary to previous reports, the risk of breast cancer was not elevated following thyroid cancer.
The risk of developing a second primary cancer was evaluated in over 250,000 persons reported to the Connecticut Tumor Registry (CTR) during 1935-82. The CTR has collected data on cancer incidence longer than any other population-based tumor registry and thus provided researchers with a unique opportunity to investigate the occurrence of second cancers among persons followed for long periods, in some cases for more than 40 years. When compared with the general Connecticut population, cancer patients had a 31% increased risk of developing a subsequent cancer overall and a 23% elevated risk of second cancer at a different site from the first. Little variation in risk was seen for the first 20 years of follow-up, although the risk for females averaged twice that for males (41% vs. 18%). Persons who survived more than 20 years after the diagnosis of their first cancer were at highest risk: 51% for females and 45% for males. Over 1 million person-years of observation were recorded, and the excess risk of developing a new cancer was 3.5 per 1,000 persons per year. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to developing new cancers in the same or contiguous tissue throughout their lifetimes. A notable finding was the high risk of cancers of the lung, larynx, buccal cavity, and pharynx observed among cervical cancer patients, which suggested a common etiology involving cigarette smoking. The intriguing association previously reported among cancers of the colon, uterine corpus, breast, and ovary was confirmed in our data, which indicated the possible influence of hormonal or dietary factors. Incidental autopsy findings were largely responsible for the observed excesses of second cancers of the prostate and kidney, and heightened medical surveillance of cancer patients likely resulted in ascertainment bias and elevated risks for some tumors during the early period of follow-up, most notably cancers of the thyroid. Interestingly, patients with prostate cancer were the only ones found to be at significantly low risk for second cancer development. However, this might be an artifact of case-finding because advanced age at initial diagnosis of prostate cancer was associated with an underascertainment of second cancers.(ABSTRACT TRUNCATED AT 400 WORDS)
The current standard for exposure to coke oven emissions sets a permissible exposure of 150 micrograms benzene-soluble fraction of total particulate matter/m3. The major epidemiologic study that formed the basis for this standard including a review of the evidence of a dose-response relationship between exposure to coal tar pitch volatiles and lung cancer is reviewed. Particular attention was given to the selection of the cohort, follow-up procedures, and the evolution of the analysis.
The patterns of cancer risk by religion in the large multidenominational population of Los Angeles County were examined with the method of proportional incidence. Risk estimates for individual cancers by religion were screened and those extreme but stable estimates found were reexamined in light of relative socioeconomic class, nativity, and ethnicity. Within Protestant denominations, gradients which can still best be attributed to religious preference were observed for leukemia, stomach, and cervix cancer. Roman Catholics tend to have high risks of stomach and gallbladder and a low risk of prostate cancer, whereas Eastern Orthodox women trade high risk of stomach cancer for low risk of endometrial and lung cancer. The most extreme pattern of risk, that for Jews, is comprised of lowered risk for cervical cancer and for most sites usually associated with smoking, plus consistently higher risk for lymphomas, thyroid cancer, and bladder cancer among males. Like Jews, Seventh-Day Adventists experience high risk for lymphoma and low risk for cervical and respiratory cancers. Risk to Mormons in Los Angeles differs from that of the standard Protestant population in only minor and inconsistent ways. Neither Mormons nor Adventists showed the previously reported deficits of colorectal or breast cancer. Although the method of proportional incidence may be partly responsible for our failure to confirm previous findings, nonreligious cultural or methodologic factors in the original investigations also provide plausible explanations. More generally, associations of the modest magnitude observed between cancer risk and religion in American populations should probably not be attributed to religious life-style, unless extraordinary circumstances permit the exclusion of other determinants.
Critical decisions made 20 years ago by those who planned the randomized trial at the Health Insurance Plan (HIP) of Greater New York to determine the efficacy of periodic screening for breast cancer are detailed. These decisions affected the age group to be screened, screening modalities, frequency of screening, sample size, primary measures for testing efficacy, and period of follow-up (long term). Results of follow-up, 16 years after entry, indicate that mortality due to breast cancer continues to be lower among study women than controls. Numerically, the differential has been stable; relatively, it has decreased. It is estimated that the study group would have experienced about a 30% reduction in breast cancer mortality if screening had been maintained. Relative case survival rates over a 14-year period after diagnosis show changes in contours of trend lines that result from screening. The study group's trend is slightly concave in contrast to the usual convex curve for the controls. The contour of the curve is more decidedly concave among subjects detected through mammography alone than for other subgroups detected through screening, although the relative survival rate remains highest in the mammography only group. Uncertainty persists about effects of screening in the HIP study on breast cancer mortality among women aged 40-49 years at entry.
