Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project

Kaposi sarcoma (KS) is a virus-related malignancy which most frequently arises in skin, though visceral sites can also be involved. Infection with Kaposi sarcoma herpes virus (KSHV or HHV-8) is required for development of KS. Nowadays, most cases worldwide occur in persons who are immunosuppressed, usually because of HIV infection or as a result of therapy to combat rejection of a transplanted organ, but classic Kaposi sarcoma is predominantly a disease of the elderly without apparent immunosuppression. We analyzed 2667 KS incident cases diagnosed during 1995–2002 and registered by 75 population-based European cancer registries contributing to the RARECARE project. Total crude and age-standardized incidence rate was 0.3 per 100,000 per year with an estimated 1642 new cases per year in the EU27 countries. Age-standardized incidence rate was 0.8 per 100,000 in Southern Europe but below 0.3 per 100,000 in all other regions. The elevated rate in southern Europe was attributable to a combination of classic Kaposi sarcoma in some Mediterranean countries and the relatively high incidence of AIDS in several countries. Five-year relative survival for 2000–2002 by the period method was 75%. More than 10,000 persons were estimated to be alive in Europe at the beginning of 2008 with a past diagnosis of KS. The aetiological link with suppressed immunity means that many people alive following diagnosis of KS suffer comorbidity from a pre-existing condition. While KS is a rare cancer, it has a relatively good prognosis and so the number of people affected by it is quite large. Thus it provides a notable example of the importance of networking in diagnosis, therapy and research for rare cancers.     

Second malignant neoplasms after cancer in childhood or adolescence. Nordic Society of Paediatric Haematology and Oncology Association of the Nordic Cancer Registries.

OBJECTIVE--To assess the relative risk of developing a second malignant neoplasm in people with a diagnosis of cancer in childhood and adolescence. DESIGN--Register based follow up study. SETTING--Populations of Nordic countries. SUBJECTS--30,880 people under the age of 20 with a first malignant neoplasm diagnosed during the period 1943-87. MAIN OUTCOME MEASURES--Relative and attributable risks of second malignant neoplasms by type of first cancer, age at first diagnosis, calendar period, sex, and country. Expected figures were based on the appropriate national incidence rates for cancer. RESULTS--247 cases of second malignant neoplasms were observed in 238 patients, yielding a relative risk for cancer of 3.6 (95% confidence interval 3.1 to 4.1). The risk changed significantly from 2.6 in people first diagnosed during the 1940s and 1950s to 6.9 among cohort members included in the late 1970s and 1980s. Increases were observed for most types of cancer. Highest levels of the relative risk were seen during the 10 years immediately after first malignant diagnosis. The incidence of second malignant neoplasms attributable to the first cancer and associated treatments, however, showed a consistent rise throughout the 45 years of follow up. CONCLUSION--The estimated risks for a second malignant neoplasm were significantly lower than those found in most large hospital based studies but compatible with the results from a similar population based study in the United Kingdom. Extent of risk and cancer pattern were similar among the Nordic countries and are believed to be representative for a large part of the European population.     

Childhood thyroid cancer, radiation dose from Chernobyl, and dose uncertainties in Bryansk Oblast, Russia: a population-based case-control study

A population-based case-control study was conducted to estimate the radiation-related risk of thyroid cancer in persons who were exposed in childhood to (131)I from the Chernobyl accident of April 26, 1986 and to investigate the impact of uncertainties in individual dose estimates. Included were all 66 confirmed cases of primary thyroid cancer diagnosed from April 26, 1986 through September 1998 in residents of Bryansk Oblast, Russia, who were 0-19 years old at the time of the accident, along with two individually matched controls for each case. Thyroid radiation doses, estimated using a semi-empirical model based on environmental contamination data and individual characteristics, ranged from 0.00014 Gy to 2.73 Gy and had large uncertainties (median geometric standard deviation 2.2). The estimated excess relative risk (ERR) associated with radiation exposure, 48.7/Gy, was significantly greater than 0 (P = 0.00013) but had an extremely wide 95% confidence interval (4.8 to 1151/Gy). Adjusting for dose uncertainty nearly tripled the ERR to 138/Gy, although this was likely an overestimate due to limitations in the modeling of dose uncertainties. The radiation-related excess risk observed in this study is quite large, especially if the uncertainty of dose estimation is taken into account, but is not inconsistent with estimates previously reported for risk after (131)I exposure or acute irradiation from external sources.     

Promoting action of radiation in the atomic bomb survivor carcinogenesis data?

The age-time patterns of risk in the atomic bomb survivor data on incidence of solid cancers suggest an action of low-LET radiation not only on the initiating event but also on promotion in a biologically motivated model that allows for both actions. The favored model indicates a decrease of radiation risks with age at exposure due to the initiating effect and with time since exposure due to the promoting effect. These result in a relative risk that depends mostly on attained age for ages at exposure above 20 years. According to the model, a dose of 100 mGy is inducing about the same number of initiating events that occur spontaneously in 1 year. Assuming that several mutations are needed to obtain intermediate cells with growth advantage does not improve the quality of fit. The estimated promoting effect could be explained if the number of intermediate cells increases by 80% at 1 Gy, e.g. due to stimulated cell repopulation.     

Joint effects of radiation and smoking on lung cancer risk among atomic bomb survivors

Results are given on the joint effect of radiation exposure and cigarette smoking on lung cancer risks among A-bomb survivors, based on 592 cases through 1994. Information on smoking was derived from mail surveys and clinical interviews of 45113 persons in the Radiation Effects Research Foundation cohort. Radiation and smoking effects on lung cancer are found to be significantly sub-multiplicative and quite consistent with additivity. The smoking relative risk, previously very low in studies of this cohort, is now similar to that found in Western populations. This increase is likely to be related to the scarcity of cigarettes during and after the war. The smoking relative risk depends little on sex. After adjusting for smoking, the radiation-related risks relative to background rates for nonsmokers are similar to those for other solid cancers: a sex-averaged ERR/Sv of about 0.9 with a female:male sex ratio of about 1.6. Adjusting for smoking removes a spuriously large female:male ratio in radiation relative risk due to confounding between sex and smoking level. The adjustment also removes an artifactual age-at-exposure effect in the radiation relative risk, opposite in direction to other cancers, which is due to birth cohort variation in lung cancer rates.     

Modelling of carcinogenesis and low-dose hypersensitivity: an application to lung cancer incidence among atomic bomb survivors

Lung cancer incidence among the atomic bomb survivors from Hiroshima and Nagasaki was analysed with the two-step clonal expansion (TSCE) model of carcinogenesis. For the baseline incidence, a new set of model parameters is introduced, which can be determined with a higher precision than the parameter sets previously used. The effect of temporal changes in the smoking behaviour on the lung cancer incidence is modelled by allowing initiation, inactivation and division rates of intermediate cells to depend on the year of birth. The TSCE model is further developed by implementing low-dose hypersensitivity in the survival of lung epithelial cells. According to the model fit to the data, the acute gamma exposure of the atomic bomb survivors does not only result in the conventional initiating effect, but also in a promoting effect for lung cancer. Compared to the model in which radiation acts merely on initiation, the new model is in better agreement with the age-at-exposure dependence in the data, and it does not predict an unexpected increase of the excess relative risk (ERR) at 40 years after exposure. According to the new model, the ERR at low doses increases non-linearly with dose, especially during the first 10 years after exposure to older persons.     

Liver cancers in Mayak workers

Liver cancer mortality risks were evaluated in 11,000 workers who started working at the "Mayak" Production Association in 1948-1958 and who were exposed to both internally deposited plutonium and external gamma radiation. Comparisons with Russian liver cancer incidence rates indicate excess risk, especially among those with detectable plutonium body burdens and among female workers in the plutonium plant. Comparisons within the Mayak worker cohort which evaluate the role of plutonium body burden with adjustment for cumulative external dose indicate excess risk among workers with burdens estimated to exceed 7.4 kBq (relative risk = 17; 95% CI = 8. 0-36) and among workers in the plutonium plant who did not have routine plutonium monitoring data based on urine measurements (relative risk = 2.8; 95% CI = 1.3-6.2). In addition, analyses treating the estimated plutonium body burden as a continuous variable indicate increasing risk with increasing burden (P < 0.001). Relative risks tended to be higher for females than for males, probably because of the lower baseline risk and the higher levels of plutonium measured in females. Because of limitations in current plutonium dosimetry, no attempt was made to quantify liver cancer risks from plutonium in terms of organ dose, and risk from external dose could not be reliably evaluated.     

Radiation-induced skin carcinomas of the head and neck

Radiation exposures to the scalp during childhood for tinea capitis were associated with a fourfold increase in skin cancer, primarily basal cell carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma, however, was not significantly elevated. Overall, 80 neoplasms were identified from an extensive search of the pathology logs of all major hospitals in Israel and computer linkage with the national cancer registry. Radiation dose to the scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy), and incidence rates were contrasted with those observed in 16,000 matched comparison subjects. The relative risk of radiogenic skin cancer did not differ significantly between men or women or by time since exposure; however, risk was greatest following exposures in early childhood. After adjusting for sex, ethnic origin, and attained age, the estimated excess relative risk was 0.7 per Gy and the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk per Gy of radiation-induced skin cancer was intermediate between the high risk found among whites and no risk found among blacks in a similar study conducted in New York City (Shore et al., Radiat. Res. 100, 192-204, 1984). This finding suggests the role that subsequent exposure to uv radiation likely plays in the expression of a potential radiation-induced skin malignancy.     

Sweetened beverage consumption and risk of liver cancer by diabetes status: A pooled analysis

BackgroundConsumption of sweetened beverages has been linked to several risk factors for liver cancer including diabetes. Studies investigating the role of sweetened beverage consumption and liver cancer, however, are limited. As persons with diabetes are advised against consumption of sugar, the objective of this study was to examine the role of sweetened beverage consumption and liver cancer risk by diabetes status.MethodsData from two U.S. cohorts: the NIH-AARP Diet and Health Study, and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were harmonized and pooled. Hazard ratios and 95%CI were estimated using Cox proportional hazard models stratified by median follow-up time.ResultsAmong persons without diabetes, there were no statistical evidence of associations between liver cancer and consumption of sweetened beverages overall, sugar sweetened beverages (SSB), or artificially sweetened beverages (ASB). Sugar sweetened (SS) soda consumption, however, was associated with liver cancer in the first follow-up interval (HR:1.18. 95%CI: 1.03, 1.35). In contrast, among persons with diabetes, there were significant associations between liver cancer and consumption of sweetened beverages overall (HR: 1.12, 95%CI 1.01, 1.24), ASBs (HR: 1.13, 95% CI: 1.02, 1.25), soda overall (HR: 1.13, 95% CI: 1.00, 1.26) and artificially sweetened (AS) soda (HR: 1.13, 95% CI: 1.01, 1.27) in the first follow-up interval.ConclusionsIncreased soda consumption may be associated with risk of liver cancer. The results suggest that decreasing consumption of SS soda by persons without diabetes, and AS soda by persons with diabetes, could be associated with reduced liver cancer risk.     

Estimated life expectancy and risk of death from cancer by quartiles in the older Japanese population: 2010 vital statistics

Data on life expectancies and risk of death from cancer are essential information to have when making informed decisions about cancer screening and treatment options, but has never been presented in a way that is readily available to use for physicians in Japan. We provided estimates of life expectancies and predicted risk of death from seven most common types of cancer (lung, gastric, liver, colon, prostate, breast, and cervical) by quartiles for the older Japanese population above 50 years old, using 2010 life tables and cancer mortality statistics data. We found that there was a large difference in life expectancy between older persons in the upper and lower quartiles. Risk of death from breast cancer was low. By using this data, physicians can more accurately obtain life expectancy estimates by assessing which quartile the patient is most likely to fall under, and help patients make better informed decisions.     

Thyroid neoplasia following low-dose radiation in childhood

The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benign tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY-cGy.     

Cancer mortality risk among workers at the Mayak nuclear complex

At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P < 0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P < 0.001) and 0.08 per gray (P < 0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.     

Studies of the mortality of atomic bomb survivors. report 12, part I. Cancer: 1950-1990

This continues the series of periodic general reports on cancer mortality in the cohort of A-bomb survivors followed by the Radiation Effects Research Foundation. The follow-up is extended by the 5 years 1986-1990, and analysis includes an additional 10,500 survivors with recently estimated radiation doses. Together these extensions add about 550,000 person-years of follow-up. The cohort analyzed consists of 86,572 subjects, of which about 60% have dose estimates of at least 0.005 Sv. During 1950-1990 there have been 3086 and 4741 cancer deaths for the less than and greater than 0.005 Sv groups, respectively. It is estimated that among these there have been approximately 420 excess cancer deaths during 1950-1990, of which about 85 were due to leukemia. For cancers other than leukemia (solid cancers), about 25% of the excess deaths in 1950-1990 occurred during the last 5 years; for those exposed as children this figure is nearly 50%. For leukemia only about 3% of the excess deaths in 1950-1990 occurred in the last 5 years. Whereas most of the excess for leukemia occurred in the first 15 years after exposure, for solid cancers the pattern of excess risk is apparently more like a life-long elevation of the natural age-specific cancer risk. Taking advantage of the lengthening follow-up, increased attention is given to clarifying temporal patterns of the excess cancer risk. Emphasis is placed on describing these patterns in terms of absolute excess risk, as well as relative risk. For example: (a) although it is becoming clearer that the excess relative risk for those exposed as children has declined over the follow-up, the excess absolute risk has increased rapidly with time; and (b) although the excess relative risk at a given age depends substantially on sex and age at exposure, the age-specific excess absolute risk depends little on these factors. The primary estimates of excess risk are now given as specific to sex and age at exposure, and these include projections of dose-specific lifetime risks for this cohort. The excess lifetime risk per sievert for solid cancers for those exposed at age 30 is estimated at 0.10 and 0.14 for males and females, respectively. Those exposed at age 50 have about one-third these risks. Projection of lifetime risks for those exposed at age 10 is more uncertain. Under a reasonable set of assumptions, estimates for this group range from about 1.0-1.8 times the estimates for those exposed at age 30. The excess life-time risk for leukemia at 1 Sv for those exposed at either 10 or 30 years is estimated as about 0.015 and 0.008 for males and females, respectively. Those exposed at age 50 have about two-thirds that risk. Excess risks for solid cancer appear quite linear up to about 3 Sv, but for leukemia apparent nonlinearity in dose results in risks at 0.1 Sv estimated at about 1/20 of those for 1.0 Sv. Site-specific risk estimates are given, but it is urged that great care be taken in interpreting these, because most of their variation can be explained simply by imprecision in the estimates.     

Risk of cancer of the breast after legal abortion during first trimester: a Swedish register study.

An increase in induced abortions in Sweden has been accompanied by an increase in the incidence of breast cancer of about 40% in women aged 20-44. To assess whether the apparent risk is real the risk of breast cancer was investigated in practically all Swedish women with a history of a legal abortion in the first trimester before the age of 30 during 1966-74 (n = 49,000). The cohort was followed up in the Swedish cancer register to identify cases of breast cancer diagnosed more than five years after the abortion until the end of 1984. The number of observed cases of breast cancer was 65 compared with an expected number of 84.5, estimated from the contemporary Swedish population with due consideration to age, giving a relative risk of 0.8 (95% confidence interval 0.58 to 0.99). Contrary to most earlier reports, this study did not indicate any overall increased risk of breast cancer after an induced abortion in the first trimester in young women.     

Radiation and smoking effects on lung cancer incidence by histological types among atomic bomb survivors

While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1-4.6) for small-cell carcinoma, 0.75 (0.3-1.3) for adenocarcinoma, and 0.27 (0-1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses.     

Lung cancer risk in mice: analysis of fractionation effects and neutron RBE with a biologically motivated model

Data from Argonne National Laboratory on lung cancer in 15,975 mice with acute and fractionated exposures to gamma rays and neutrons are analyzed with a biologically motivated model with two rate-limiting steps and clonal expansion. Fractionation effects and effects of radiation quality can be explained well by the estimated kinetic parameters. Both an initiating and a promoting action of neutrons and gamma rays are suggested. While for gamma rays the initiating event is described well with a linear dose-rate dependence, for neutrons a nonlinear term is needed, with less effectiveness at higher dose rates. For the initiating event, the neutron RBE compared to gamma rays is about 10 when the dose rate during each fraction is low. For higher dose rates this RBE decreases strongly. The estimated lifetime relative risk for radiation-induced lung cancers from 1 Gy of acute gamma-ray exposure at an age of 110 days is 1.27 for male mice and 1.53 for female mice. For doses less than 1 Gy, the effectiveness of fractionated exposure to gamma rays compared to acute exposure is between 0.4 and 0.7 in both sexes. For lifetime relative risk, the RBE from acute neutrons at low doses is estimated at about 10 relative to acute gamma-ray exposure. It decreases strongly with dose. For fractionated neutrons, it is lower, down to about 4 for male mice.     

Do Lung Cancer Eligibility Criteria Align with Risk among Blacks and Hispanics?

Background

Black patients have higher lung cancer risk despite lower pack years of smoking. We assessed lung cancer risk by race, ethnicity, and sex among a nationally representative population eligible for lung cancer screening based on Medicare criteria.

Methods

We used data from the National Health and Nutrition Examination Survey, 2007–2012 to assess lung cancer risk by sex, race and ethnicity among persons satisfying Medicare age and pack-year smoking eligibility criteria for lung cancer screening. We assessed Medicare eligibility based on age (55–77 years) and pack-years (≥30). We assessed 6-year lung cancer risk using a risk prediction model from Prostate, Lung, Colorectal and Ovarian Cancer Screening trial that was modified in 2012 (PLCO_m2012). We compared the proportions of eligible persons by sex, race and ethnicity using Medicare criteria with a risk cut-point that was adjusted to achieve comparable total number of persons eligible for screening.

Results

Among the 29.7 million persons aged 55–77 years who ever smoked, we found that 7.3 million (24.5%) were eligible for lung cancer screening under Medicare criteria. Among those eligible, Blacks had statistically significant higher (4.4%) and Hispanics lower lung cancer risk (1.2%) than non-Hispanic Whites (3.2%). At a cut-point of 2.12% risk for lung screening eligibility, the percentage of Blacks and Hispanics showed statistically significant changes. Blacks eligible rose by 48% and Hispanics eligible declined by 63%. Black men and Hispanic women were affected the most. There was little change in eligibility among Whites.

Conclusion

Medicare eligibility criteria for lung cancer screening do not align with estimated risk for lung cancer among Blacks and Hispanics. Data are urgently needed to determine whether use of risk-based eligibility screening improves lung cancer outcomes among minority patients.     

Extrapolation of the relative risk of radiogenic neoplasms across mouse strains and to man

We have examined two interrelated questions: is the susceptibility for radiogenic cancer related to the natural incidence, and are the responses of cancer induction by radiation described better by an absolute or a relative risk model. Also, we have examined whether it is possible to extrapolate relative risk estimates across species, from mice to humans. The answers to these questions were obtained from determinations of risk estimates for nine neoplasms in female and male C3Hf/Bd and C57BL/6 Bd mice and from data obtained from previous experiments with female BALB/c Bd and RFM mice. The mice were exposed to 137Cs gamma rays at 0.4 Gy/min to doses of 0, 0.5, 1.0, or 2.0 Gy. When tumors that were considered the cause of death were examined, both the control and induced mortality rates for the various tumors varied considerably among sexes and strains. The results suggest that in general susceptibility is determined by the control incidence. The relative risk model was significantly superior in five of the tumor types: lung, breast, liver, ovary, and adrenal. Both models appeared to fit myeloid leukemia and Harderian gland tumors, and neither provided good fits for thymic lymphoma and reticulum cell sarcoma. When risk estimates of radiation-induced tumors in humans and mice were compared, it was found that the relative risk estimates for lung, breast, and leukemia were not significantly different between humans and mice. In the case of liver tumors, mice had a higher risk than humans. These results indicate that the relative risk model is the appropriate approach for risk estimation for a number of tumors. The apparent concordance of relative risk estimates between humans and mice for the small number of cancers examined encourages us to undertake further studies.     

Exposure to ionizing radiation and brain cancer incidence: The Life Span Study cohort

BackgroundIonizing radiation is a cause of cancer. This paper examines the effects of radiation dose and age at exposure on the incidence of brain cancer using data from the Life Span Study (LSS) of atomic bomb survivors.MethodsThe Radiation Effects Research Foundation website provides demographic details of the LSS population, estimated radiation doses at time of bomb in 1945, person years of follow-up and incident cancers from 1958 to 1998. We modelled brain cancer incidence using background-stratified Poisson regression, and compared the excess relative risk (ERR) per Gray (Gy) of brain dose with estimates from follow-up studies of children exposed to diagnostic CT scans.ResultsAfter exposure to atomic bomb radiation at 10 years of age the estimated ERR/Gy was 0.91 (90%CI 0.53, 1.40) compared with 0.07 (90%CI −0.27, 0.56) following exposure at age 40. Exposure at 10 years of age led to an estimated excess of 17 brain tumors per 100,000 person year (pyr) Gy by 60 years of age. These LSS estimates are substantially less than estimates based on follow-up of children exposed to CT scans.ConclusionEstimates of ERR/Gy for brain cancers in the LSS and haemangioma cohorts seem much smaller than estimates of risk for young persons in the early years after exposure to CT-scans. This could be due to reverse causation bias in the CT cohorts, diagnostic error, measurement error with radiation doses, loss of early follow-up in the LSS, or non-linearity of the dose-response curve.     

Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13.

The penetrance of the BRCA2 gene on chromosome 13q12-13 has been estimated in two large, systematically ascertained, linked families, by use of a maximum-likelihood method to incorporate both cancer-incidence data and 13q marker typings in the families. The cumulative risk of breast cancer in female gene carriers was estimated to be 59.8% by age 50 years (95% confidence interval [95% CI] 25.9%-78.5%) and 79.5% by age 70 years (95% CI 28.9%-97.5%). The cumulative risk of breast cancer in male carriers was estimated to be 6.3% (95% CI 1.4%-25.6%) by age 70 years. There was no evidence of any risk difference between the two families. These results indicate that the lifetime breast cancer risk in BRCA2 carriers, for at least a subset of mutations, is comparable to that for BRCA1. A significant excess of ovarian cancer in gene carriers was observed (relative risk 17.69, based on three cases), but the absolute risk of ovarian cancer was less than that reported for BRCA1. Significant excesses of laryngeal cancer (relative risk 7.67, based on two possible carriers) and prostate cancer (relative risk 2.89, based on five possible carriers) were also observed. One case of ocular melanoma, as well as a second eye cancer of unspecified histology, occurred in obligate gene carriers.