B. J. Stone

Bone sarcomas linked to radiotherapy and chemotherapy in children

We estimated the risk of subsequent bone cancer among 9170 patients who had survived two or more years after the diagnosis of a cancer in childhood. As compared with the general population, the patients had a relative risk of 133 (95 percent confidence interval, 98 to 176) and a mean (+/- SE) 20-year cumulative risk of 2.8 +/- 0.7 percent. Detailed data on treatment were obtained on 64 patients in whom bone cancer developed after childhood cancer. As compared with 209 matched controls who had survived cancer in childhood but who did not have bone cancer later, patients who had had radiation therapy had a 2.7-fold risk (95 percent confidence interval, 1.0 to 7.7) and a sharp dose-response gradient reaching a 40-fold risk after doses to the bone of more than 6000 rad. The relative dose-response effect among patients who had been treated for retinoblastoma resembled that among patients with all other types of initial tumors, although the cumulative risk of bone cancer in the retinoblastoma group was higher. Similar numbers of patients were treated with orthovoltage and megavoltage; the patterns of risk among categories of doses did not differ according to the type of voltage. After adjustment for radiation therapy, treatment with alkylating agents was also linked to bone cancer (relative risk, 4.7; 95 percent confidence interval, 1.0 to 22.3), with the risk increasing as cumulative drug exposure rose. We conclude that both radiotherapy and chemotherapy with alkylating agents for childhood cancer increase the subsequent risk of bone cancer.

The Relation between Survival and Age at Diagnosis in Breast Cancer

We analyzed the relation between age at diagnosis and relative survival (ratio of observed to expected survival) in 57,068 women in Sweden in whom breast cancer was diagnosed in 1960 to 1978 (about 98 percent of all cases). Women who were 45 to 49 years old had the best prognosis, with a relative survival exceeding that of the youngest patients (less than 30 years) by 7.6 to 12.9 percent at different periods of observation. Relative survival declined markedly after the age of 49--particularly in women aged 50 to 59--and the oldest women (greater than 75) had the worst rate. The difference in relative survival between those older than 75 and those 45 to 49 increased from 8.6 percent at 2 years to 12.2, 20.3, and 27.5 percent after 5, 10, and 15 years of follow-up, respectively. The long-term annual mortality rate due to breast cancer approached 1 to 2 percent at the premenopausal ages but exceeded 5 percent throughout the period of observation in the oldest age group. An understanding of the biologic basis for the complex relation between age and prognosis might provide a better understanding of the natural history of breast cancer in women.

Occupation and prostate cancer risk in Sweden.

To provide new leads regarding occupational prostate cancer risk factors, we linked 36,269 prostate cancer cases reported to the Swedish National Cancer Registry during 1961 to 1979 with employment information from the 1960 National Census. Standardized incidence ratios for prostate cancer, within major (1-digit), general (2-digit), and specific (3-digit) industries and occupations, were calculated. Significant excess risks were seen for agriculture-related industries, soap and perfume manufacture, and leather processing industries. Significantly elevated standardized incidence ratios were also seen for the following occupations: farmers, leather workers, and white-collar occupations. Our results suggest that farmers; certain occupations and industries with exposures to cadmium, herbicides, and fertilizers; and men with low occupational physical activity levels have elevated prostate cancer risks. Further research is needed to confirm these findings and identify specific exposures related to excess risk in these occupations and industries.

Mortality among dust-exposed Chinese mine and pottery workers.

A cohort study of approximately 68,000 persons employed during 1972 to 1974 at metal mines and pottery factories in south central China was conducted to evaluate mortality from cancer and other diseases among workers exposed to different levels of silica and other dusts. A follow-up of subjects through December 31, 1989 revealed 6,192 deaths, a number close to that expected based on Chinese national mortality rates. There was, however, a nearly 6-fold increase in deaths from pulmonary heart disease (standard mortality ratio, 581; 95% confidence interval 538 to 626), and a 48% excess of mortality from nonmalignant respiratory diseases (standard mortality ratio, 148; 95% confidence interval, 139 to 158), primarily because of a more than 30-fold excess of pneumoconiosis. Pulmonary heart disease and noncancerous respiratory disease rates rose in proportion to dust exposure. Cancer mortality overall was not increased among the miners or pottery workers. There was no increased risk of lung cancer, except among tin miners, and trends in risk of this cancer with increasing level of dust exposure were not significant. Risks of lung cancer were 22% higher among workers with than without silicosis. The findings indicate that respiratory disease continues to be an occupational hazard among Chinese miners and pottery workers, but that cancer risks are not as yet strongly associated with work in these dusty trades.

Incidence of childhood cancer in twins

The incidence of childhood cancer in twins was evaluated by linking a roster of 30,925 twins born in Connecticut (United States) between 1930 and 1969 with the Connecticut Tumor Registry. Cancer, exclusive of nonmelanoma skin cancer, was identified in 19 females and 12 males under 15 years of age. The incidence rate among twins was 7.9 cancers per 100,000 person-years (PY) overall, and 9.7 and 6.1 per 100,000 PYs for females and males, respectively. Four of 13 leukemias occurred in two female twin pairs, representing concordance rates of 18 percent overall and 29 percent for like-sex pairs, which are somewhat higher than values reported previously. The number of cancers expected was computed on the assumption that twins experienced the same sex-, age-, and calendar time-specific cancer rates as recorded for all Connecticut-born children. Because active follow-up of individuals was not conducted, an adjustment to person-years of observation was made to account for childhood mortality, including the high perinatal mortality characteristie of twins. Childhood cancer was 30 percent less frequent than expected (standardized incidence ratio [SIR]=0.7; 95 percent confidence interval [CI]=0.5–0.9), a deficit that is marginally greater than those found in previous studies. Both leukemia (SIR=0.8; CI=0.4–1.4), and all other cancers combined (SIR=0.6; CI=0.3–0.9) occurred less often than expected. The deficit was greater among males (SIR=0.5; CI=0.2–0.8) than among females (SIR=0.9; CI=0.5–1.4) and was especially pronounced among males younger than five years (SIR=0.2; CI=0.0–0.7). The data support the view that twins, particularly male twins, have a lower risk of childhood cancer than single-born children. Any added risk for twins associated with their greater frequency of exposure to prenatal X-rays appears to have been insufficient to offset an ‘effect’ of twinning per se. Possible explanations for this finding include (i) the low birthweight distribution of twins, or (ii) selective early mortality of twin fetuses or neonates who would otherwise have developed a clinical cancer.

Age as a prognostic factor in breast cancer.

Long‐term survival was evaluated in a total of 12,319 women with first breast cancer, comprising 94.9% of virtually all women with first breast cancers diagnosed in Sweden in 1959 through 1963. After correction for the expected mortality, it was found that age at diagnosis was an important predictor of the probability of escaping the risk of dying of breast cancer (relative survival), with a regular trend toward a more favorable course in younger women. This difference between the age groups is apparent as early as 5 years after diagnosis and increases throughout the period of observation. Thus the relative 20‐year survival rates ± 95% confidence limits were 51.3 ± 3.8%, 41.2 ± 3.4%, 34.2 ± 3.8%, and 16.6 ± 6.3% at ages 40 through 44, 50 through 54, 60 through 69, and 70 through 79 years, respectively. Patients younger than 40 years diverged from the general trend, with a survival rate of 44.1 ± 4.6% at 20 years.

Geographic correlates of pancreas cancer in the United States

Age‐adjusted death rates for pancreas cancer during 1950–69 were correlated by sex and race with demographic and industrial data for the 3,056 counties of the contiguous United States. Only a small fraction of the county‐to‐county variation in mortality was explained by these variables, in contrast to their strong correlation with other common neoplasms. The only geographic cluster occurred in an area encompassing parts of Louisiana and Mississippi. Throughout the country, however, the rates for pancreas cancer were higher in urban areas, especially in males, and in counties with many residents of Scandinavian and East European (particularly Russian) descent. No associations were found with socioeconomic, industrial, or alcohol‐consumption indices. The mortality patterns for pancreas and lung cancers were highly correlated in males, suggesting the influence of tobacco consumption on both tumors. In females, pancreas cancer was significantly correlated with diabetes mellitus, consistent with other evidence linking these two diseases.

Respiratory cancer among copper smelter workers: recent mortality statistics.

A survey of mortality among copper smelter workers in the western United States revealed that a respiratory cancer excess previously observed during the period 1938 through 1963 continued from 1964 through 1977. When analyzed in relation to smelter employment prior to 1964, the recent increase in respiratory cancer was linked to work in plant areas where airborne arsenic concentrations were elevated and to a cumulative arsenic exposure index, although some excess risk was also associated with long-term employment in jobs with limited exposures to arsenic. The arsenic-related excess remained after adjustment for work in areas of the plant with elevated concentrations of sulphur dioxide, which was not found to have an independent influence upon cancer risk. Increased rates for nonmalignant respiratory disease were also observed, but were not significantly associated with arsenic exposure.

Cancer risks among iron and steel workers in Anshan, China, Part I: Proportional mortality ratio analysis

A standardized proportional mortality ratio (SPMR) study of 8,887 deaths during 1980-1989 among male workers in a large integrated iron-steel complex in Anshan, China, was conducted to provide clues to occupational risk factors. Accidents and cancer accounted for a higher proportion of deaths among the iron-steel workers than among the general male population (SPMR = 1.21; 95% CI = 1.12-1.31 and 1.14; 95% CI = 1.10-1.18, respectively). Among all workers, SPMRs were significantly elevated for stomach, lung, and colorectal cancers (SPMR = 1.37, 1.37, 1.38, respectively), but not other cancers. Risks of stomach cancer appeared to be highest among workers employed in jobs with exposure to iron and coal dust, whereas significant increases in colorectal cancer were seen for loading and other dusty jobs and for administrative and sedentary jobs without dust exposure. Risks of lung cancer appeared increased for a variety of jobs throughout the complex, especially those with probable high levels of exposure to polycyclic hydrocarbons and asbestos. Risk of esophageal cancer was significantly elevated for fire-resistant brick makers, and risk of nonmalignant respiratory disease was significantly elevated for those employed as furnace workers, foundry workers, and fire-resistant brick makers.

Cancer mortality in U.S. counties with shipyard industries during World War II

Abstract Respiratory cancer mortality, 1950–1969, was consistently high in U.S. counties where shipyards were engaged in the construction and repair of large naval and cargo vessels during World War II. Over three-fourths of the shipyard counties had elevated rates (in comparison to rates in counties of similar population size in the same region of the country) for lung and laryngeal cancer among white males, with the excess particularly evident in the South. Mortality from lung cancer was high also among white females, and the rate of increase in both sexes was greater than recorded nationally. In addition, rates for oropharyngeal, esophageal, and gastric cancers tended to be elevated in the shipyard counties, but mortality from other tumors was roughly comparable to national levels. A causal relation to asbestos exposures in shipyards cannot be inferred from this correlational analysis, but the unusual mortality patterns underscore the need for broadly based analytic studies to evaluate the risk of cancer in persons with wartime shipyard employment.