Response to Tsuda et al. "demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the toolkit for detecting misused epidemiological methods".

BACKGROUND: The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) European project was conducted in 2015-2017 to review the lessons learned from the experience of past nuclear accidents and develop recommendations for preparedness and health surveillance of populations affected by a nuclear accident. Using a toolkit approach, Tsuda et al. recently published a critical review of the article by Cléro et al. derived from the SHAMISEN project on thyroid cancer screening after nuclear accident. MAIN BODY: We address the main points of criticism of our publication on the SHAMISEN European project. CONCLUSION: We disagree with some of the arguments and criticisms mentioned by Tsuda et al. We continue to support the conclusions and recommendations of the SHAMISEN consortium, including the recommendation not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it.

Coverage rate of opportunistic and organised breast cancer screening in France: Department-level estimation.

OBJECTIVE: In France, the national breast cancer screening programme (NBCSP), targeting women aged 50-74 years was rolled out nationwide in 2004. It aims at reducing breast cancer mortality. In addition to the NBCSP, the use of opportunistic screening is permitted in France. The objective of this study is to estimate both opportunistic use and overall coverage rates of breast cancer screening, among women 40-84 years of age, in France. METHODS: The French medico-administrative health data system (SNDS) was used to identify women performing an opportunistic or organised mammography screening in France in 2016-2017. RESULTS: The two-yearly opportunistic mammography screening is 18 % among women aged 40-84; it is 11 % among women aged 50-74, i.e., the target age range for organised screening, 36 % among women aged 40-49 and 13 % among women aged 75-84. The overall two-yearly screening coverage is 48 % for all women aged 40-84; it is 60 % among women aged 50-74, 36 % among women 40-49 and 16 % for those aged 75-84. Geographical variations in screening are lessened when the two screening strategies are considered, as they balance each other. CONCLUSION: Although coverage in the NBCSP is around 50 % in France, more than one third of the women make use of opportunistic screening within and outside the target age range. Organized screening appears to improve equity of access to mammography screening service. The lack of data on opportunistic screening practices hinders the evaluation of French screening practices as a whole.

Care pathway of women with interval breast cancer in 2016, based on medico-administrative data.

BACKGROUND: Since 2004, an organised screening programme (OS) for breast cancer has been in place for 50-74 years women who are not at an increased risk. Despite this, 17% of cancers diagnosed within 24 months following an OS mammogram are interval cancers (IC), diagnosed even though the OS had not reported cancer. After identifying IC from the French administrative healthcare database (SNDS), our objective was to describe the care pathways of women with IC in 2016. MATERIALS AND METHODS: The IC identification algorithm is based on breast imaging tests conducted in the 24 months prior to diagnosis and on the compatibility of their timeline with ACR3 lesion follow-up (BIRADS guidelines). The care pathways of 3 groups were compared: women with IC, diagnosed through the OS, and diagnosed outside the OS programme (personalised screening or based on clinical signs, PSCS group). RESULTS: Respectively, 12,965 (46%), 3433 (12%), and 11,761 women (42%) were classified in the OS, IC and PSCS groups, i.e. 20.9% IC cases among the women taking part in the OS programme. The women from the IC group presented with more forms with lymph node or metastatic involvement than those of the OS group. Their pathways were more complex than in the OS group: at an equivalent stage, more total mastectomies and more adjuvant or neoadjuvant chemotherapy regimens. CONCLUSION: The care pathways of women with IC are intermediate with respect to those of the OS or PSCS group.Cases of IC probably include several cancer prognosis profiles.

Lessons learned from Chernobyl and Fukushima on thyroid cancer screening and recommendations in case of a future nuclear accident.

Exposure of the thyroid gland to ionizing radiation at a young age is the main recognized risk factor for differentiated thyroid cancer. After the Chernobyl and Fukushima nuclear accidents, thyroid cancer screening was implemented mainly for children, leading to case over-diagnosis as seen in South Korea after the implementation of opportunistic screening (where subjects are recruited at healthcare sites). The aim of cancer screening is to reduce morbidity and mortality, but screening can also cause negative effects on health (with unnecessary treatment if over-diagnosis) and on quality of life. This paper from the SHAMISEN special issue (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) presents the principles of cancer screening, the lessons learned from thyroid cancer screening, as well as the knowledge on thyroid cancer incidence after exposure to iodine-131. The SHAMISEN Consortium recommends to envisage systematic health screening after a nuclear accident, only when appropriately justified, i.e. ensuring that screening will do more good than harm. Based on the experience of the Fukushima screening, the consortium does not recommend mass or population-based thyroid cancer screening, as the negative psychological and physical effects are likely to outweigh any possible benefit in affected populations; thyroid health monitoring should however be made available to persons who request it (regardless of whether they are at increased risk or not), accompanied with appropriate information and support.

The risk of cancer attributable to diagnostic medical radiation: Estimation for France in 2015.

Although medical ionizing radiation (IR) has clear clinical benefits, it is an established carcinogen. Our study estimates the number of new cancer cases in France in 2015 attributable to IR exposure from medical procedures. Exposures from external (X-rays, CT scans, interventional radiology) and internal (nuclear medicine) sources were considered. We used 2007 national frequencies of diagnostic examinations by sex and age to estimate the lifetime organ dose exposure adjusted for changes in the use of such procedures over time. The Biological Effects of Ionizing Radiation VII risk models were used to estimate the corresponding excess cancer risk, assuming an average latency period of 10 years. Additionally, we used cancer incidence data from the French Cancer Registries Network. Of the 346,000 estimated new cancer cases in adults in France in 2015, 2300 cases (940 among men and 1360 among women) were attributable to diagnostic IR, representing 0.7% of all new cancer cases (0.5% for men and 0.9% for women). The leading cancers attributable to medical IR were female breast (n = 560 cases), lung (n = 500 cases) and colon (n = 290 cases) cancers. Compared to other risk factors, the contribution of medical IR to the cancer burden is small, and the benefits largely outweigh its harms. However, some of these IR-associated cancer cases may be preventable through dose optimization of and enhanced justification for diagnostic examinations.

Cancers related to lifestyle and environmental factors in France in 2015.

BACKGROUND: Cancer is a major cause of premature illness and death in France. To quantify how cancer prevention could reduce the burden, we present estimates of the contribution of lifestyle and environmental risk factors to cancer incidence in France in 2015, comparing these with other high-income countries. METHOD: Prevalences of, and relative risks for tobacco smoking, alcohol consumption, inadequate diet, overweight and obesity, physical inactivity, exogenous hormones, suboptimal breastfeeding, infectious agents, ionising radiation, air pollution, ultraviolet exposure, occupational exposures, arsenic in drinking water and indoor benzene were obtained to estimate the population attributable fraction (PAF) and the number of attributable cancers by the cancer site and sex. RESULTS: In 2015, 41% (or 142,000 of 346,000) of all new cancers diagnosed in France could be attributed to the aforementioned risk factors. The numbers and PAF were slightly higher in men than in women (84,000 versus 58,000 cases and 44% versus 37%, respectively). Smoking (PAF: 20%), alcohol consumption (PAF: 8%), dietary factors (PAF: 5%) and excess weight (PAF: 5%) were the most important factors. Infections and occupational exposures each contributed to an additional 4% of the cancer cases in 2015. CONCLUSION: Today, two-fifths of cancers in France are attributable to preventable risk factors. The variations in the key amenable factors responsible in France relative to other economically similar countries highlight the need for tailored approaches to cancer education and prevention. Reducing smoking and alcohol consumption and the adoption of healthier diet and body weight remain important targets to reduce the increasing number of new cancer patients in France in the decades to follow.

Breast cancer screening programme participation and socioeconomic deprivation in France.

The objective was to quantify the relationship between deprivation and national breast cancer screening programme (NBCSP) participation at an ecological level in mainland France. Data from 4,805,390 women-living in 36,209 municipalities within 95 departments-participating in the 2013-2014 NBCSP were analysed using the French Deprivation Index (FDep). FDep population quintiles by municipality were computed to describe NBCSP participation according to deprivation. To better examine the relationship between continuous value of deprivation index and participation rates at the municipality level, we built a generalized linear mixed model. Geographical variations in participation rates were marked. The national standardized participation rate was higher in the intermediate quintiles (55%), 45% for the least deprived one and 52% for the most deprived one. Using our model, we also obtained an inverted U-curve for the relationship between NBCSP participation and municipality deprivation: participation was lower for both the least and most deprived municipalities. This relationship was also observed for each of the two subpopulations-urban municipalities and rural ones-considered separately. Introducing the FDep in the model reduced slightly the unexplained variations in participation rates between departments and between municipalities (with a proportional change in variance of 14% and 12% respectively). We highlight major disparities in departmental participation rates and FDep/participation profiles. However, deprivation appears to have only little influence on geographical variation in participation rates. There is a need to further understand the factors affecting geographical variation in participation rates, in particular the use of opportunistic screening.

The impact of historical breastfeeding practices on the incidence of cancer in France in 2015.

PURPOSE: The purpose of the study was to estimate the number of new breast cancer cases in France in 2015 attributable to breastfeeding for durations below recommendations (at least 6 months per child), and cases prevented through historical breastfeeding. As a secondary analysis, the corresponding numbers for ovarian cancer were estimated. METHODS: Historical breastfeeding data were obtained from population surveys. Duration of breastfeeding data were obtained from the French Épifane cohort study. Relative risks were obtained from meta-analyses, cohort, and case-control studies. Cancer incidence data were obtained from the French Network of Cancer Registries. A 10-year latency period was assumed. RESULTS: Among parous women 25 years of age and older, 14.1% breastfed for at least 6 months per child born before 2006. As a result, 1,712 new breast cancer cases (3.2% of all new breast cancer cases) were attributable to breastfeeding for < 6 months per child, while actual breastfeeding practices prevented 765 breast cancer cases. Furthermore, 411 new ovarian cancer cases (8.6% of all new ovarian cancer cases) may be attributable to breastfeeding for < 6 months per child, with breastfeeding preventing 163 ovarian cancer cases. CONCLUSIONS: The historically low breastfeeding prevalence and duration in France led to numerous avoidable cancer cases.

Incidence of major smoking-related cancers: trends among adults aged 20-44 in France from 1982 to 2012.

BACKGROUND: Tobacco is currently the largest risk factor for cancers of the lung, lip/oral cavity/pharynx (LOCP) and esophagus. Variations in tobacco consumption over time have led to changes in cancer incidence in the general population. Data on the incidence of cancers at these sites in adults aged 20-44 years old are scarce. Our objective was to provide estimates of incidence trends for these cancers in France among this age group over the last 30 years. METHODS: Observed incidence data over the period 1982-2010 for the 20-44 age group were provided from six cancer registries (eight for esophagus) covering approximately 6% of the French population. Age-period-cohort models were used on the observed period, and estimates of cancer incidence for France in 2012 were provided on the basis of short-term predictions. RESULTS: In men, a sharp decline was observed over time for LOCP and esophageal cancers, while lung cancer saw only a slight decline. In women, a large increase was seen in lung cancer incidence, while LOCP cancer incidence did not vary significantly. CONCLUSION: Smoking behaviors among adults aged 20-44 impact incidence trends in cancers of the lung, LOCP and esophagus, although other factors are involved, particularly in LOCP and esophageal cancers. Our results highlight the importance of preventative efforts which particularly target women aged 20-44. Efforts to curb tobacco smoking in men should also be pursued.

Cancer incidence estimation at a district level without a national registry: a validation study for 24 cancer sites using French health insurance and registry data.

BACKGROUND: District-level cancer incidence estimation is an important issue in countries without a national cancer registry. This study aims to both evaluate the validity of district-level estimations in France for 24 cancer sites, using health insurance data (ALD demands--Affection de Longue Durée) and to provide estimations when considered valid. Incidence is estimated at a district-level by applying the ratio between the number of first ALD demands and incident cases (ALD/I ratio), observed in those districts with cancer registries, to the number of first ALD demands available in all districts. These district-level estimations are valid if the ratio does not vary greatly across the districts or if variations remain moderate compared with variations in incidence rates. METHODS: Validation was performed in the districts covered by cancer registries over the period 2000-2005. The district variability of the ALD/I ratio was studied, adjusted for age (mixed-effects Poisson model), and compared with the district variability in incidence rate. The epidemiological context is also considered in addition to statistical analyses. RESULTS: District-level estimation using the ALD/I ratio was considered valid for eight cancer sites out of the 24 studied (lip-oral cavity-pharynx, oesophagus, stomach, colon-rectum, lung, breast, ovary and testis) and incidence maps were provided for these cancer sites. CONCLUSION: Estimating cancer incidence at a sub-national level remains a difficult task without a national registry and there are few studies on this topic. Our validation approach may be applied in other countries, using health insurance or hospital discharge data as correlate of incidence.

Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri.

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.

Relationship between occupational exposure to ionizing radiation and mortality at the French electricity company, period 1961-2003.

PURPOSE: Epidemiological studies in nuclear industry workers can produce relevant information to better appreciate the health risks related to chronic external exposure to low doses of ionizing radiation (IR). This work examined the relations between exposure to IR and mortality in workers at the French Electricity Company (EDF), followed up to year 2003. METHODS: Permanent staff who had worked for at least 1 year at EDF during period 1961-1994 and who had been monitored for exposure to IR were included (n = 22,393). One-sided trend tests for mortality according to cumulative dose and relative risks at 100 mSv were estimated using Poisson regression. Main analyses were stratified on age, sex, calendar time and education. RESULTS: A total of 874 deaths occurred, and 66 workers were lost to follow-up. Median age at end of follow-up was 48. None of the causes of death investigated increased significantly according to dose, except cerebrovascular diseases (p = 0.01), but this last observation was based on only 22 cases. CONCLUSIONS: These results do not allow dismissing a possible influence of IR on cancer risk in this population. The cohort is still relatively young and therefore confidence intervals for estimated relative risks remain wide, although they have considerably narrowed since a previous analysis. Chance is a possible explanation for the association between IR and cerebrovascular mortality, due to the low number of cases on which it is based. These results thus need to be stabilized by conducting joint analyses with similar cohorts.

Radon-associated lung cancer risk among French uranium miners: modifying factors of the exposure-risk relationship.

Radon is classified as a known pulmonary carcinogen in humans. A better understanding of the effects of low exposure and time-dependent factors, modifying the lung cancer risk is of continued interest. We present analyses of the exposure-risk relationship in the French cohort of uranium miners updated until 1999 and including five additional years of follow-up. These new analyses provide a better opportunity to look at low radon exposures with longer follow-up intervals, and allow consideration of new modifying factors, such as physical activity, mine location and job type. The cohort includes 5,086 miners, and 159 lung cancer deaths have been observed among these over a follow-up of more than 30 years. The exposure-risk relationship was estimated using excess relative risk models, which allow investigation of several modifying factors such as period of exposure, time since exposure, age at exposure, duration of exposure, exposure rate, job type, mine type and physical activity. The analysis confirms the association between radon exposure and lung cancer risk (ERR per 100 WLM = 0.58, P < 0.01). Period of exposure and physical activity appear as major modifying factors. Higher risks are observed for hard physical activity works. The effect of hard physical activity persists when the period of exposure is taken into account (ERR per 100 WLM = 2.95, P < 0.01).

Ionizing radiation and risk of chronic lymphocytic leukemia in the 15-country study of nuclear industry workers.

In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external ionizing radiation dose within the 15-country nuclear workers cohort study. The analyses included, in seven countries with CLL deaths, a total of 295,963 workers with more than 4.5 million person-years of follow-up and an average cumulative bone marrow dose of 15 mSv; there were 65 CLL deaths in this cohort. The relative risk (RR) at an occupational dose of 100 mSv compared to 0 mSv was 0.84 (95% CI 0.39, 1.48) under the assumption of a 10-year exposure lag. Analyses of longer lag periods showed little variation in the RR, but they included very small numbers of cases with relatively high doses. In conclusion, the largest nuclear workers cohort study to date finds little evidence for an association between low doses of external ionizing radiation and CLL mortality. This study had little power due to low doses, short follow-up periods, and uncertainties in CLL ascertainment from death certificates; an extended follow-up of the cohorts is merited and would ideally include incident cancer cases.

Lung cancer in French and Czech uranium miners: Radon-associated risk at low exposure rates and modifying effects of time since exposure and age at exposure.

Radon is recognized as a public health concern for indoor exposure. Precise quantification derived from occupational exposure in miners is still needed for estimating the risk and the factors that modify the dependence on cumulated exposure. The present paper reports on relationship between radon exposure and lung cancer risk in French and Czech cohorts of uranium miners (n = 10,100). Miners from these two cohorts are characterized by low levels of exposure (average cumulated exposure of less than 60 WLM) protracted over a long period (mean duration of exposure of 10 years) and by a good quality of individual exposure estimates (95% of annual exposures based on radon measurements). The modifying effect of the quality of exposure on the risk is analyzed. A total of 574 lung cancer deaths were observed, which is 187% higher than expected from the national statistics. This significantly elevated risk is strongly associated with cumulated radon exposure. The estimated overall excess relative risk per WLM is 0.027 (95% CI: 0.017-0.043, related to measured exposures). For age at exposure of 30 and 20 years since exposure, the ERR/WLM is 0.042, and this value decreases by approximately 50% for each 10-year increase in age at exposure and time since exposure. The present study emphasizes that the quality of exposure estimates is an important factor that may substantially influence results. Time since exposure and simultaneously age at exposure were the most important effect modifiers. No inverse exposure-rate effect below 4 WL was observed. The results are consistent with estimates of the BEIR VI report using the concentration model at an exposure rate below 0.5 WL.

Cancer mortality risk among biology research workers in France: first results of two retrospective cohorts studies.

OBJECTIVE: To investigate all-cause and cancer mortality of biological research laboratories workers of the French Atomic Energy Commission (CEA) and the National Institute of Health and Medical Research (INSERM). METHODS: Two cohorts, bioCEA (N = 3,509) and bioINSERM (N = 4,966) were followed from 1968 to 1994 and 1980 to 1993, respectively. The mortality of each cohort was compared with that of the French population by computation of the standardized mortality ratio (SMR) with their 90% confidence interval (90% CI). Trend and heterogeneity tests were computed in order to study SMRs variation by job characteristics. In the bioCEA cohort individual dosimetry data being available, a trend test was also computed according to ionizing radiation cumulative dose. RESULTS: The SMRs were significantly below one in both cohorts for all-cause mortality (bioCEA: SMR = 0.52 [0.46-0.59], bioINSERM: SMR = 0.56 [0.46-0.67]) and for all-cancer mortality (bioCEA: SMR = 0.66 [0.54-0.80], bioINSERM: SMR = 0.55 [0.39-0.75]). There were some specific cancer sites for which the SMR was higher than 1, but not significantly. In the bioCEA cohort a positive trend was observed between ionizing radiation cumulative doses and all-cause as well as all-cancer SMRs. CONCLUSION: This study on two French cohorts of biological research workers found a favorable mortality pattern. These findings are consistent with recent publications. The positive trend of cancer mortality according to ionizing radiation exposure among bioCEA cohort needs to be confirmed with more precise assessment of exposures and information on individual risk factors.

Lung cancer attributable to indoor radon exposure in france: impact of the risk models and uncertainty analysis.

OBJECTIVE: The inhalation of radon, a well-established human carcinogen, is the principal-and omnipresent-source of radioactivity exposure for the general population of most countries. Scientists have thus sought to assess the lung cancer risk associated with indoor radon. Our aim here is to assess this risk in France, using all available epidemiologic results and performing an uncertainty analysis. METHODS: We examined the exposure-response relations derived from cohorts of miners and from joint analyses of residential case-control studies and considered the interaction between radon and tobacco. The exposure data come from measurement campaigns conducted since the beginning of the 1980s by the Institute for Radiation Protection and Nuclear Safety and the Directorate-General of Health in France. We quantified the uncertainties associated with risk coefficients and exposures and calculated their impact on risk estimates. RESULTS: The estimated number of lung cancer deaths attributable to indoor radon exposure ranges from 543 [90% uncertainty interval (UI) , 75-1,097] to 3,108 (90% UI, 2,996-3,221) , depending on the model considered. This calculation suggests that from 2.2% (90% UI, 0.3-4.4) to 12.4% (90% UI, 11.9-12.8) of these deaths in France may be attributable to indoor radon. DISCUSSION: In this original work we used different exposure-response relations from several epidemiologic studies and found that regardless of the relation chosen, the number of lung cancer deaths attributable to indoor radon appears relatively stable. Smokers can reduce their risk not only by reducing their indoor radon concentration but also by giving up smoking.