Marie Sanchez

Estimates of the cancer burden in Europe from radioactive fallout from the Chernobyl accident

The Chernobyl accident, which occurred April 26, 1986, resulted in a large release of radionuclides, which were deposited over a very wide area, particularly in Europe. Although an increased risk of thyroid cancer in exposed children has been clearly demonstrated in the most contaminated regions, the impact of the accident on the risk of other cancers as well as elsewhere in Europe is less clear. The objective of the present study was to evaluate the human cancer burden in Europe as a whole from radioactive fallout from the accident. Average country‐ and region‐specific whole‐body and thyroid doses from Chernobyl were estimated using new dosimetric models and radiological data. Numbers of cancer cases and deaths possibly attributable to radiation from Chernobyl were estimated, applying state‐of‐the‐art risk models derived from studies of other irradiated populations. Simultaneously, trends in cancer incidence and mortality were examined over time and by dose level. The risk projections suggest that by now Chernobyl may have caused about 1,000 cases of thyroid cancer and 4,000 cases of other cancers in Europe, representing about 0.01% of all incident cancers since the accident. Models predict that by 2065 about 16,000 (95% UI 3,400–72,000) cases of thyroid cancer and 25,000 (95% UI 11,000–59,000) cases of other cancers may be expected due to radiation from the accident, whereas several hundred million cancer cases are expected from other causes. Although these estimates are subject to considerable uncertainty, they provide an indication of the order of magnitude of the possible impact of the Chernobyl accident. It is unlikely that the cancer burden from the largest radiological accident to date could be detected by monitoring national cancer statistics. Indeed, results of analyses of time trends in cancer incidence and mortality in Europe do not, at present, indicate any increase in cancer rates—other than of thyroid cancer in the most contaminated regions—that can be clearly attributed to radiation from the Chernobyl accident.

The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk

This paper examines the effects of systematic and random errors in recall and of selection bias in case–control studies of mobile phone use and cancer. These sensitivity analyses are based on Monte–Carlo computer simulations and were carried out within the INTERPHONE Study, an international collaborative case–control study in 13 countries. Recall error scenarios simulated plausible values of random and systematic, non-differential and differential recall errors in amount of mobile phone use reported by study subjects. Plausible values for the recall error were obtained from validation studies. Selection bias scenarios assumed varying selection probabilities for cases and controls, mobile phone users, and non-users. Where possible these selection probabilities were based on existing information from non-respondents in INTERPHONE. Simulations used exposure distributions based on existing INTERPHONE data and assumed varying levels of the true risk of brain cancer related to mobile phone use. Results suggest that random recall errors of plausible levels can lead to a large underestimation in the risk of brain cancer associated with mobile phone use. Random errors were found to have larger impact than plausible systematic errors. Differential errors in recall had very little additional impact in the presence of large random errors. Selection bias resulting from underselection of unexposed controls led to J-shaped exposure–response patterns, with risk apparently decreasing at low to moderate exposure levels. The present results, in conjunction with those of the validation studies conducted within the INTERPHONE study, will play an important role in the interpretation of existing and future case–control studies of mobile phone use and cancer risk, including the INTERPHONE study.

Quantifying the Impact of Selection Bias Caused by Nonparticipation in a Case–Control Study of Mobile Phone Use

PURPOSE To quantitatively assess the impact of selection bias caused by nonparticipation in a multinational case-control study of mobile phone use and brain tumor. METHODS Non-response questionnaires (NRQ) were completed by a sub-set of nonparticipants. Selection bias factors were calculated based on the prevalence of mobile phone use reported by nonparticipants with NRQ data, and on scenarios of hypothetical exposure prevalence for other nonparticipants. RESULTS Regular mobile phone use was reported less frequently by controls and cases who completed the NRQ (controls, 56%; cases, 50%) than by those who completed the full interview (controls, 69%; cases, 66%). This relationship was consistent across study centers, sex, and age groups. Lower education and more recent start of mobile phone use were associated with refusal to participate. Bias factors varied between 0.87 and 0.92 in the most plausible scenarios. CONCLUSIONS Refusal to participate in brain tumor case-control studies seems to be related to less prevalent use of mobile phones, and this could result in a downward bias of around 10% in odds ratios for regular mobile phone use. The use of simple selection bias estimation methods in case-control studies can give important insights into the extent of any bias, even when nonparticipant information is incomplete.

Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France.

Background There is extensive epidemiological evidence that menopausal hormone therapy (MHT) increases breast cancer risk, particularly combinations of estrogen and progestagen (EP). We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen), and time interval between onset of menopause and start of MHT were examined. Methods We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls). Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated. Results We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49) for progesterone-derived and 3.35 (1.07-10.4) for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment. Conclusion This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.

Breast cancer risk, nightwork, and circadian clock gene polymorphisms.

Night shift work has been associated with an increased risk of breast cancer pointing to a role of circadian disruption. We investigated the role of circadian clock gene polymorphisms and their interaction with nightwork in breast cancer risk in a population-based case-control study in France including 1126 breast cancer cases and 1174 controls. We estimated breast cancer risk associated with each of the 577 single nucleotide polymorphisms (SNPs) in 23 circadian clock genes. We also used a gene- and pathway-based approach to investigate the overall effect on breast cancer of circadian clock gene variants that might not be detected in analyses based on individual SNPs. Interactions with nightwork were tested at the SNP, gene, and pathway levels. We found that two SNPs in RORA (rs1482057 and rs12914272) were associated with breast cancer in the whole sample and among postmenopausal women. In this subpopulation, we also reported an association with rs11932595 in CLOCK, and with CLOCK, RORA, and NPAS2 in the analyses at the gene level. Breast cancer risk in postmenopausal women was also associated with overall genetic variation in the circadian gene pathway (P=0.04), but this association was not detected in premenopausal women. There was some evidence of an interaction between PER1 and nightwork in breast cancer in the whole sample (P=0.024), although the effect was not statistically significant after correcting for multiple testing (P=0.452). Our results support the hypothesis that circadian clock gene variants modulate breast cancer risk.

Tea and coffee consumption and risk of oral cavity cancer: results of a large population-based case-control study, the ICARE study.

BACKGROUND Results on the relationship between coffee and tea drinking and the risk of oral cavity cancer are contrasted. The aim of this study was to evaluate the relation between coffee and tea drinking and the risk of oral cavity cancer in France, a high incidence area. MATERIAL AND METHODS We conducted a population based case-control study with face-to-face interviews and standardized questionnaires (the ICARE study, Investigation of occupational and environmental causes of respiratory cancers). We used data from 689 cases of oral cavity squamous cell carcinoma and 3481 controls. Odds-ratios (ORs) and 95% confidence intervals (95% CI) associated with tea and coffee consumption (quantity, duration, cumulative consumption) were estimated by unconditional logistic regression with adjustment for age, gender, area of residence, education, body mass index, tobacco smoking and alcohol drinking. RESULTS We observed inverse associations between oral cavity cancer and tea or coffee consumption (odds ratio, 0.39; 95% CI 0.21-0.70, for the highest quartile of tea consumption, and 0.60, 95% CI 0.34-1.05, for the highest quartile of coffee consumption). Exclusive tea or coffee consumption was associated with a reduced risk of oral cavity cancer and their joint effect was multiplicative. No differences in risk between men and women or between consumers of tobacco and alcohol and non-consumers were observed. The odds ratios related to the subsites usually included in the oropharynx (soft palate and base of the tongue) did not differ significantly from that observed for the other subsites of the oral cavity. CONCLUSIONS Tea and coffee drinking may decrease the risk of oral cavity cancer through antioxidant components which play a role in the repair of cellular damages. These findings need further investigation in prospective studies and the underlying mechanisms in humans remain to be clarified.

Exposure to chlorinated solvents and lung cancer: results of the ICARE study

Objective To investigate the role of occupational exposure to chlorinated solvents in lung cancer aetiology. Methods ICARE (Investigation of occupational and environmental CAuses of REspiratory cancers) is a French, multicentre, population-based, case–control study. Information on the lifelong work history of 2926 cases and 3555 controls was collected using standardised questionnaires. Occupational exposures were assessed using job-exposure matrices for five chlorinated solvents. Solvents were studied separately and in combinations. ORs were computed using unconditional logistic regression models adjusted for classic risk factors, including a history of cigarette smoking and exposure to asbestos. Adjustment for socioeconomic status (SES) was also made. Results After adjustment for exposure to asbestos, we observed a positive, statistically significant association with lung cancer for men and women exposed to a combination of perchloroethylene (PCE), trichloroethylene and dichloromethane (DCM). Further adjustment for SES slightly decreased this association. In contrast, no statistically significant associations were found for other solvent combinations. Conclusions These results suggest that exposure to PCE may constitute a risk factor for lung cancer, especially among women, who seem to have a higher prevalence of exposure than men.

Family history of cancer, personal history of medical conditions and risk of oral cavity cancer in France: the ICARE study.

BackgroundThe aim of this study was to evaluate the role of family history of cancer and personal history of other medical conditions in the aetiology of the oral cavity cancer in France.MethodsWe used data from 689 cases of oral cavity squamous cell carcinoma and 3481 controls included in a population-based case–control study, the ICARE study. Odds-ratios (ORs) associated with family history of cancer and personal medical conditions and their 95% confidence intervals (95% CI) were estimated by unconditional logistic regression and were adjusted for age, gender, area of residence, education, body mass index, tobacco smoking and alcohol drinking.ResultsPersonal history of oral candidiasis was related to a significantly increased risk of oral cavity cancer (OR 5.0, 95% CI 2.1-12.1). History of head and neck cancers among the first-degree relatives was associated with an OR of 1.9 (95% CI 1.2-2.8). The risk increased with the number of first-degree relatives with head and neck cancer.ConclusionA family history of head and neck cancer is a marker of an increased risk of oral cavity cancer and should be taken into account to target prevention efforts and screening. Further studies are needed to clarify the association between oral cavity cancer and personal history of candidiasis.

Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals

Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.Meta-analysis of data from 58,265 cattle shows that the genetic architecture underlying stature is similar to that in humans, where many genomic regions individually explain only a small amount of phenotypic variance.

Welding, a risk factor of lung cancer: the ICARE study

Objectives We investigated the relationship between lung cancer and occupational exposure to welding activity in ICARE, a population-based case–control study. Methods Analyses were restricted to men (2276 cases, 2780 controls). Welding exposure was assessed through detailed questionnaires, including lifelong occupational history. ORs were computed using unconditional logistic regression, adjusted for lifelong cigarette smoking and occupational exposure to asbestos. Results Among the regular welders, welding was associated with a risk of lung cancer (OR=1.7, 95% CI 1.1 to 2.5), which increased with the duration (OR=2.0, 95% CI 1.0 to 3.9 when duration >10 years), and was maximum 10–20 years since last welding. The risk was more pronounced in case of gas welding (OR=2.0, 95% CI 1.2 to 3.3), when the workpiece was covered by paint, grease, or other substances (OR=2.0, 95% CI 1.2 to 3.4) and when it was cleaned with chemical substances before welding. No statistically significant increase in lung cancer risk was observed among occasional welders. Conclusions Although these results should be confirmed, we showed that type of welding and mode of workpiece preparation are important determinants of the lung cancer risk in regular welders.