Between 1920 and 1959, 9675 women were irradiated in infancy for skin hemangioma at Radiumhemmet, Stockholm. They were exposed to low to moderate doses of ionizing radiation. The mean age at first exposure was 6 months and the mean absorbed dose to the breast anlage was 0.39 Gy (range or = 50 years after exposure the ERR at 1 Gy was 2.25 (95% CI 0.59-5.62). The fitted excess absolute risk (EAR) was 22.9 per 10(4) breast-year gray. The breast absorbed dose and time after exposure were important risk determinants for breast cancer excess risk. Forty to 50 years of follow-up was necessary for the excess risk to be expressed. The study confirms previous findings that the breast anlage of female infants is sensitive to ionizing radiation.
The relation between breast cancer risk and serum levels of cholesterol and beta-lipoprotein (BLP), height, weight, Quetelet's index and blood pressure was studied in a cohort of 46,570 Swedish women less than 75 years of age. The cohort was examined between 1963 and 1965 and followed up in the Swedish Cancer Registry until 1983. During this period 1,182 cases of breast cancer were reported. Of those, 196 were reported among women less than 50 years of age. Statistically significant positive associations were observed between height, weight, and systolic blood pressure and breast cancer risk. No clear trend in cancer risk related to serum cholesterol or BLP was seen in the total material. In a stepwise Cox multiple regression analysis only the associations with height and blood pressure remained significant. Among women, having their cancer diagnosed before the age of 50, higher Quetelet's index was associated with a lower cancer risk, whereas a positive correlation was seen among women greater than or equal to 50 years. In the group of younger women a high BLP level was associated with an increased risk of breast cancer. This relation became even stronger when studied in a multivariate analysis, which also showed a negative correlation between serum cholesterol and cancer risk.
The cancer incidence was studied in 18,030 patients (33% males, 67% females) with skin hemangioma who were admitted to Radiumhemmet, Karolinska Hospital, Stockholm, Sweden, 1920-1959. Radium-226 sources were used in 12,821 patients, x-ray therapy was used in 2,515 patients, and no radiotherapy was given to 2,694 patients. Cancer incidence in the cohort was searched by record linkage with the Swedish Cancer Register for the period 1958-1982. The median age was 6 months for the treated patients and 8 months for the patients not receiving radiotherapy. In the group treated with radium-226 or orthovoltage x rays (greater than or equal to 100-kV peak), 224 cancers were observed [relative risk (RR) = 1.18; 95% confidence interval (CI) = 1.03-1.35]. In patients given contact x rays, 10 cancers were observed (RR = 0.71; 95% CI = 0.34-1.30). In patients not treated with ionizing radiation, 34 cancers were observed (RR = 0.93; 95% CI = 0.64-1.29). In patients treated with radium-226 or orthovoltage x rays, an RR of 1.65 was observed for breast cancer (95% CI = 1.26-2.13) and an RR of 2.73 was found for soft tissue tumors (95% CI = 1.18-5.38). Patients with brain tumors, thyroid cancers, and bone tumors had received radiotherapy close to the tumor site more often than expected. For patients with breast cancer, no such difference was found. For cancers of the breast and thyroid, the RR was higher in patients given more than one treatment.
We studied cancer incidence and mortality from cancer and coronary heart disease in relation to serum cholesterol levels in 92,710 individuals followed-up in the nationwide Swedish Cancer Register and the Swedish Cause of Death Register for 18-20 years. According to Cox's proportional hazard model, total cancer incidence and total cancer mortality were negatively correlated to serum cholesterol level (P less than .001). The negative correlations were most pronounced during the first years of follow-up. Cancer mortality data showed a stronger negative association to cholesterol than did incidence data during the first 10 years of follow-up (P less than .05). Mortality from coronary heart disease was positively correlated to serum cholesterol (P less than .001) during the entire follow-up. In contrast to most studies that were based on mortality data, our results of the comparison of incidence and mortality data of the same cohort are in agreement with those of a cholesterol-lowering effect of a preclinical cancer. Efforts by investigators and clinicians to lower serum cholesterol to prevent cardiovascular disease are, according to the present findings, not likely to increase cancer mortality risks but would extend life, irrespective of cause of death.
Cancer incidence was studied in 10,552 patients (mean age, 57 years) who received 131I therapy (mean dose, 506 MBq) for hyperthyroidism between 1950 and 1975. Follow-up on these patients was continued for an average of 15 years. Record linkage with the Swedish Cancer Register for the period 1958-1985 identified 1543 cancers occurring 1 year or more after 131I treatment, and the standardized incidence ratio (SIR) was 1.06 (95% confidence interval = 1.01-1.11). Significantly increased SIRs were observed for cancers of the lung (SIR = 1.32; n = 105) and kidney (SIR = 1.39; n = 66). Among 10-year survivors, significantly elevated risks were seen for cancers of the stomach (SIR = 1.33; n = 58), kidney (SIR = 1.51; n = 37), and brain (SIR = 1.63; n = 30). Only the risk for stomach cancer, however, increased over time (P less than .05) and with increasing activity administered (P = not significant). The risk for malignant lymphoma was significantly below expectation (SIR = 0.53; n = 11). Overall cancer risk did not increase with administered 131I dose or with time since exposure. The absence of any increase in leukemia adds further support to the view that a radiation dose delivered gradually over time is less carcinogenic than the same total dose received over a short time. Only for stomach cancer was a possible radiogenic excess suggested.
Notes
Comment In: J Natl Cancer Inst. 1994 Jul 6;86(13):1026-78007013
Cancer risks during the period 1961-1984 were studied in a cohort of 2,034 Swedish reindeer-breeding Lapps, a unique group whose culture and life-style differ considerably from those in the rest of the Swedish population. A total of 100 cases of cancer were observed versus 163 expected. Statistically significantly decreased risks were found for cancers of the colon, respiratory organs, female breast, male genital organs, and kidneys, and for malignant lymphomas. The stomach was the only site with a significantly increased risk. Reindeer-breeding Lapps have ingested fallout products via the lichen-reindeer-man food chain since the 1950s. However, no increased risk was found for the cancer sites considered to be most sensitive to radiation.
Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of 131I. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following 131I treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of 131I with highest risk for patients exposed to greater than or equal to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose 131I exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower-dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation.
Cancer survival in Sweden in 1961-1991 is presented as a comprehensive report from the Swedish Cancer Registry. The report shows both successes and failures, confirms some earlier published results and presents some new findings worth further analysis. Survival has increased for female breast cancer, malignant melanoma, cancers of the testis and thyroid gland, acute leukemia, and Hodgkin's disease. No improvements are found for multiple myeloma or cancers of the liver, gall bladder, and pancreas. Small increases are shown for colorectal cancer and cancers of the stomach, oesophagus, and kidney. Increases in postoperative survival are shown for sites dominated by histologically benign tumors, i.e., intracranial neurinoma, meningioma, and cancers of the endocrine glands such as parathyroid tumors. From 1970-1972 to 1980-1982 the 10-year relative survival rate (RSR) increased from 30% to 38% for males and from 44% to 51% for females. Hence, cancer survival for all cases combined has approached the survival of the general population somewhat. Most of the increases took place in the 1970's. Changes in the distribution of incidence towards cancer sites with better prognoses account for some 10-20% of the observed increases in RSR, whereas the aging of the cancer population reduces the upward trend in RSR for all cases combined by some 1-2%. Cancer patients have poorer survival than the population long after 5 years of follow-up. They reach the survival of the population after about 8-12 years for colorectal cancer, 10 years for cervical cancer, 7-10 years for malignant melanoma, 13-18 years for kidney cancer, and more than 19 years for female breast and prostate cancer. For patients diagnosed in 1970-1972 this occurred 16 years after diagnosis at 29% for males and 43% for females when all cancer cases were combined. The extended time until 'statistical cure' for most cancer forms clearly indicates the need to augment the commonly used 5-year RSR with other outcome measures. If cancers on average are discovered earlier today, the 5-year RSR gives an exaggerated impression of the improvement over time. In this case the change in the 10-year RSR is a less biased criterion.
