Mortalità per cause cardiovascolari e respiratorie attribuibile all'esposizione alle emissioni di una centrale a carbone: una proposta per stimare l'accorciamento individuale di vita.

BACKGROUND: the exposure to a coal-fired power plant has been shown to increase mortality both for cardiovascular and respiratory causes among an exposed cohort in comparison with a cohort of unexposed. Hazard ratios between 1.30 and 1.90 were found for cardiovascular and respiratory mortality. OBJECTIVES: to estimate the individual life shortening among the exposed due to power plant emissions. DESIGN: survival for cardiovascular and respiratory disease in the exposed vs unexposed groups was estimated by the Kaplan-Meier method. For each gender and exposure, a fictitious cohort with a cumulative 30-year follow up was built combining three subcohorts of age at entry of 55-64, 65-74, and 75-84 years, with 10 years of follow up each. Survivals at 10 years in the 55-64-year subcohort were used as initial risks for 65-74-year subcohort; then, survivals at 10 years of the 65-74-year subcohort were used as initial risk in the 75-84-year subcohort. Eventually, 30-years cumulative follow up cohorts were obtained by gender and exposure. Individual life-shortening in people exposed was estimated as time from death of an exposed subject to the subsequent time when the unexposed cohort reached the same risk of the exposed subject at that time of the death. Here, it is proposed a method to take into account causes other than those considered. SETTING AND PARTICIPANTS: 144,018 subjects aged 55-74 years at entry of both genders belonging to the open cohort of residents of 12 municipalities (including Savona) from 2001 to 2013 in the area where the coal-fired power plant of Vado-Quiliano (Liguria Region, Northern Italy) is located. MAIN OUTCOME MEASURES: individual life shortening. RESULTS: after 5 years of follow up, the individual life shortening due to cardiorespiratory causes varied between 972 and 1,822 days for males and from 612 and 1,578 days among females. Taking into account other causes of death, reduces slightly (3% for males of 75 years at death) the estimate of life shortening found in this study. The comparison between the cohorts requires that the exposed and unexposed groups are comparable, except for the exposure, and that causes other than those considered are taken into account. Socioeconomic status had been found to have little effect on cause-specific death risk indicating that, at least in terms of socioeconomic status, the exposed and unexposed groups were similar. Taking into account causes other than those considered slightly reduced the found estimates (3% at age 75 in males). According to the proposal, the life-shortening for the considered causes is easy to calculate and provides an individual indicator of damage. Inferring from group statistics individual estimates could be the most controversial point of this approach. The proposed estimates are the most credible estimate of individual damage for each occurred death among the exposed people. CONCLUSIONS: an increased hazard ratio for a wide series of causes is equivalent to a life shortening among the exposed. A method to produce reasonable estimates of life-shortening is proposed as the effect of exposure at individual level. This approach is simple and do not require sophisticated statistical tools. It appears a promising approach for other settings.

Childhood infectious diseases and risk of non-Hodgkin's lymphoma according to the WHO classification: A reanalysis of the Italian multicenter case-control study.

Since 1960, incidence of non-Hodgkin's lymphoma (NHL) has been increasing in most industrialized countries, but causes of this trend remain unclear. A role of the decreased exposure to infectious agents during childhood has been proposed. Our study evaluates the association between common childhood infectious diseases and the risk of NHL and its major subtypes by a reanalysis of the Italian multicenter case-control study. After exclusion of next-of-kin interviews, 1,193 cases, diagnosed between 1990 and 1993, and 1,708 population-based controls were included in the analyses. OR estimates were obtained by logistic regression, adjusting for gender, age, residence area, education, smoking habit and exposure to radiations, pesticides and aromatic hydrocarbons. Among B-cell lymphomas (n = 1,102) an inverse association was observed for rubella (OR = 0.80, 95% CI: 0.65-0.99), pertussis (OR = 0.74, 95% CI: 0.62-0.88) and any infection (OR = 0.75, 95% CI: 0.61-0.93). A negative trend by number of infections was observed, which was more evident among mature B-cell lymphoma (OR = 0.66 for three infections or more, 95% CI: 0.48-0.90). Our results indicate a potential protective role of common childhood infections in the etiology of B-cell NHL.

Drinking water contamination from perfluoroalkyl substances (PFAS): an ecological mortality study in the Veneto Region, Italy.

Background: Perfluoroalkyl substances (PFAS), a heterogeneous group of highly stable man-made chemicals, have been widely used since 1960s and can be detected almost ubiquitously in all environmental matrices. In Italy, on January 2014, drinking water contamination in an area of the Veneto Region was detected mainly due to the drain of fluorinated chemicals by a manufacturing company operating since 1964. Methods: The present ecological mortality study was aimed at comparing mortality for some causes of death selected on the basis of previous reported associations, during the period 1980-2013, in municipalities with PFAS contaminated and uncontaminated drinking water on the basis of the levels indicated by the Italian National Health Institute (ISS). Sex-specific number, standardized mortality rates and rate ratios (RR) for PFAS contaminated and uncontaminated areas were computed for each cause of death through the ENEA epidemiological database. Results: In both sexes, statistically significant RRs were detected for all causes mortality, diabetes, cerebrovascular diseases, myocardial infarction and Alzheimer's disease. In females, RRs significantly higher than 1.0 were also observed for kidney and breast cancer, and Parkinson's disease. Increased risk, although not statistically significant, was observed for bladder cancer in both sexes, and for testicular cancer, pancreatic cancer and leukemia in males only. Conclusions: Higher mortality levels for some causes of death, possibly associated with PFAS exposure, were detected in contaminated municipalities in comparison with uncontaminated ones with similar socioeconomic status and smoking habits. These results warrant further individual level analytic studies to delineate casual associations.

[Rate advancement assessment: a case study]. / Valutare l'anticipazione dell'evento: un caso di studio.

OBJECTIVE: to re-evaluate the meaning of attributable risk assessing the event advancement as an individual effect indicator. DESIGN: mortality descriptive study of cardiovascular and respiratory causes in two populations exposed to different emission levels from a coal-fired power plant. SETTING AND PARTICIPANTS: people residing in 23 Italian municipalities (100,725 subjects) aged 35-84 years observed from 2000 to 2007. MAIN OUTCOME MEASURES: age-specific death rates and death anticipation by age. RESULTS: a higher mortality among the exposed corresponds to a median death anticipation from 25 to 20 months among people aged 65-74 and of 6 months for people aged 75-84. CONCLUSION: for the set of the considered causes of death, a higher mortality among the exposed corresponds to a median anticipation of all deaths occurred among exposed people.

[Female breast cancer and occupational sectors: a preliminary study in the provinces of Lombardy, Italy]. / Cancro della mammella e settori occupazionali: studio esplorativo nelle province lombarde.

BACKGROUND: The role of occupational exposures in breast cancer development is still uncertain. A recent paper showed increased risks in some occupational sectors in Lombardy, Italy. We deepened this analysis at the level of single provinces of the same Italian region. METHODS: Based on administrative data, a case-control study was carried out recruiting all incident cases of female breast cancer in the period 2002-2009, aged between 35 and 69 years, residing in Lombardy, Italy. Controls were randomly sampled from all women residing in Lombardy as of December 31, 2005. Occupational histories, including blue collar status, were available from 1974 through record linkage with a social security pension database, and were obtained for 11188 cases and 25329 controls. Adjusted odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were calculated using multiple unconditional logistic regression models. Analyses were performed also by single provinces of Lombardy, Italy. Multiple comparisons were accounted for according to the Benjamini-Hochberg method. RESULTS: The ORs for female breast cancer were modestly but significantly increased for employment in electrical manufacturing (OR 1.12, 90% CI 1.04-121), textile (OR 1.08, 90% CI 1.02-1.15), paper (OR 1.25, 90% CI 1.06-1.46) and rubber (OR 1.26, 90% CI 1.03-1.54) industries. Analysis by province showed significantly increased ORs for electrical manufacturing in the Milano province. After adjustment for multiple comparisons no estimates remained statistically significant, except OR for electrical manufacturing in the Milano province. CONCLUSIONS: Although with several limitations, our results point to a possible role of exposures in electrical manufacturing, textile, paper and rubber industries in the process leading to breast cancer. An in-dept study for the electrical manufacturing industry has been already planned in Milano province.

Occupational brain cancer risks in Umbria (Italy), with a particular focus on steel foundry workers.

OBJECTIVES: As a part of the Occupational Cancer Monitoring (OCCAM) project, a routine analysis based on Umbria region cancer registry (RTUP) database in 2002-2008 was performed. Among other results, the incidental finding of brain cancer increased risk in steel foundry workers in Terni province (Italy), lead us to deepen the analysis, focusing on this specific industrial sector. METHODS: A monitoring study, based on Umbria Regional Cancer Registry data, was recently carried out. Brain cancer cases and controls identified within this preliminary study were selected. Therefore, we considered all incident cases (in Umbria region 2002-2008) of brain cancer occurred among workers occupied for at least one year in private companies since 1974 and controls randomly sampled from the same population. Afterwards, taking in to account results from steel foundry in Terni province, we further deepened our analysis, focusing on this productive sector. Odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were calculated using multiple logistic regression models, adjusted by age at diagnosis or sampling, sex and province of residence, when appropriate. RESULTS: Statistical analyses were carried out on 14913 subjects, 56 cases and 14857 controls. Significantly increased ORs were observed for garment, mechanical manufacturing and chemical industries. Moreover, the risk estimates were strongly correlated with exposures in iron and steel foundries and a cluster of 14 cases in the same foundry in Terni was observed (OR 9.59, 90% CI 2.76-33.34). CONCLUSIONS: Results of this explorative study showed increased ORs of brain cancer in some productive branches, involving possible exposures to chemical compounds and/or solvents. Moreover, our results pointed out a significantly increased risk in Terni foundry workers, determining an interesting brain cancer cluster (14 cases). Further studies on this industrial sector are needed with improved definitions of tasks and exposures.

Childhood infectious diseases and risk of leukaemia in an adult population.

Our study is aimed at investigating the association between common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing leukaemia in an adult population. A reanalysis of a large population-based case-control study was carried out. Original data included 1,771 controls and 649 leukaemia cases from 11 Italian areas. To contain recall bias, the analysis was restricted to subjects directly interviewed and with a good quality interview (1,165 controls and 312 cases). Odds ratios (ORs) and their related 95% confidence intervals (95% CIs) were estimated by unconditional polychotomous logistic regression model adjusting for age, gender and occupational and lifestyle exposures. A protective effect of at least one infection (OR = 0.66, 95% CI: 0.45-0.97), measles (OR = 0.57, 95% CI: 0.39-0.82) and pertussis (OR = 0.66, 95% CI: 0.45-0.98) was observed for chronic lymphoid leukaemia (CLL). The number of infections was strongly inversely associated with the risk of CLL (p = 0.002, test for trend). With regard to the other types of leukaemia, only a protective effect of pertussis was observed for AML (OR = 0.52, 95% CI: 0.32-0.87). Our results pointed out a protective role of childhood infectious diseases on the risk of CLL in adults. Although a specific antioncogenic effect of some infectious disease, especially measles, cannot be ruled out, the observed decrease of risk with increasing number of infections suggests that a more general "hygiene hypothesis" could be the most likely explanation of the detected association. The protective role of pertussis remains to be elucidated.

Intake of coffee, decaffeinated coffee, or tea does not affect risk for pancreatic cancer: results from the European Prospective Investigation into Nutrition and Cancer Study.

BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer. METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression. RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers. CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.

Female breast cancer in Lombardy, Italy (2002-2009): a case-control study on occupational risks.

BACKGROUND: The role of occupational exposures in breast cancer development is still uncertain and, to our knowledge, no studies have been recently carried out in Italy to provide a comprehensive estimation of this possible risk. METHODS: Based on administrative data, a case-control study was carried out recruiting all incident cases of female breast cancer in the period 2002-2009, aged between 35 and 69 years, residing in Lombardy, Italy. Controls were randomly sampled from all women residing in Lombardy as of December 31, 2005. Occupational histories, including blue-collar status, were available from 1974 through record linkage with a social security pension database, and were obtained for 11,188 cases and 25,329 controls. Adjusted odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were calculated using multiple unconditional logistic regression models, including terms for sectors of longest employment and for duration of employment. Multiple comparisons were accounted for according to the Benjamini-Hochberg method. RESULTS: The ORs for female breast cancer were modestly but significantly increased for employment in electrical manufacturing (OR 1.12, 90%CI 1.04-1.21), textile (OR 1.08, 90%CI 1.02-1.15), paper (OR 1.25, 90%CI 1.06-1.46) and rubber (OR 1.26, 90%CI 1.03-1.54) industries. Analysis by duration of employment within sectors showed significantly increased ORs for electrical manufacturing and rubber industries. After adjustment for multiple comparisons no estimates remained statistically significant. CONCLUSIONS: Although with several limitations, our results point to a possible role of exposures in electrical manufacturing, textile, paper and rubber industries in the process leading to breast cancer. An in-dept study for the electrical manufacturing industry has been already planned.

[Multiple sclerosis and occupational exposures: results of an explorative study]. / Sclerosi multipla e esposizioni occupazionali: risultati di uno studio preliminare.

OBJECTIVES: The aim of the study is to explore possible relationships between occupational exposures and Multiple Sclerosis (MS), whose etiology is not well defined yet. To date, only few literature data are available on this subject. METHODS: We carried out a case-control study, where cases were MS patients included in the MS Register of the Province of Pavia, Northern Italy, and controls, 1:4 matched by sex and age (5 years classes), were randomly selected from the National Health Service population files. The occupational histories were obtained from Italian Institute for Social Security (INPS) archives by automatic linkage using Italian Occupational Cancer Monitoring (OCCAM) method that estimates the risk of specific occupational cancers, by geographic area and industrial sector. OR adjusted for sex and age and corresponding 90% confidence intervals were used to estimate the association between exposure and disease. RESULTS: We included in the study 227 MS patients (130 (57.3%) female, 97 (42.7%) male) and 907 controls (514 (56.7%) female, 393 (43.3%) male). Our results suggest an increased risk for men in mechanical manufacturing industry (OR 1.71, 90% CI 1.03-2.85) and agriculture (OR 2.47, 90% CI 1.03-5.91). Women show an increased risk in mechanical manufacturing industry (OR 2.05, 90% CI 1.22-3.45), agriculture (OR 2.57, 90% CI 1.09-6.09) and leather/shoe industry (OR 2.34, 90% CI 1.06-5.20). CONCLUSIONS: Our preliminary findings indicate that solvent exposures could be related to the risk of MS, as both shoe/leather workers and mechanical manufacturing industry workers are exposed to organic solvents. Interestingly, a major risk of MS was also found among workers engaged in agriculture, suggesting a role of pesticides, whose neurotoxic effect is well known.

Fatty liver index and mortality: the Cremona study in the 15th year of follow-up.

UNLABELLED: A fatty liver, which is a common feature in insulin-resistant states, can lead to chronic liver disease. It has been hypothesized that a fatty liver can also increase the rates of non-hepatic-related morbidity and mortality. Therefore, we wanted to determine whether the fatty liver index (FLI), a surrogate marker and a validated algorithm derived from the serum triglyceride level, body mass index, waist circumference, and γ-glutamyltransferase level, was associated with the prognosis in a population study. The 15-year all-cause, hepatic-related, cardiovascular disease (CVD), and cancer mortality rates were obtained through the Regional Health Registry in 2011 for 2074 Caucasian middle-aged individuals in the Cremona study, a population study examining the prevalence of diabetes mellitus in Italy. During the 15-year observation period, 495 deaths were registered: 34 were hepatic-related, 221 were CVD-related, 180 were cancer-related, and 60 were attributed to other causes. FLI was independently associated with the hepatic-related deaths (hazard ratio = 1.04, 95% confidence interval = 1.02-1.05, P < 0.0001). Age, sex, FLI, cigarette smoking, and diabetes were independently associated with all-cause mortality. Age, sex, FLI, systolic blood pressure, and fibrinogen were independently associated with CVD mortality; meanwhile, age, sex, FLI, and smoking were independently associated with cancer mortality. FLI correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), a surrogate marker of insulin resistance (Spearman's ρ = 0.57, P < 0.0001), and when HOMA-IR was included in the multivariate analyses, FLI retained its association with hepatic-related mortality but not with all-cause, CVD, and cancer-related mortality. CONCLUSION: FLI is independently associated with hepatic-related mortality. It is also associated with all-cause, CVD, and cancer mortality rates, but these associations appear to be tightly interconnected with the risk conferred by the correlated insulin-resistant state.

Lung cancer risk in the electroplating industry in Lombardy, Italy, using the Italian occupational cancer monitoring (OCCAM) information system.

BACKGROUND: Occupational Cancer Monitoring (OCCAM) is an Italian organization that monitors occupational cancers, by area and industrial sector, by retrieving cases and employment history from official databases. OCCAM previously estimated a relative risk (RR) of lung cancer of about 1.32 among "metal treatment" workers in Lombardy, northern Italy, potentially exposed to chrome and nickel. In the present study, lung cancer risk was estimated among electroplating workers only. METHODS: Lombardy electroplating companies were identified from descriptions in Social Security files. Lung cancer risk was evaluated from 2001 to 2008 incident cases identified from hospital discharge records. RESULTS: The RR for lung cancer among electroplating workers was 2.03 (90% CI 1.33-3.10, 18 cases) for men; 3.00 (90% CI 1.38-9.03, 4 cases) for women. CONCLUSIONS: Electroplaters had higher risks than "metal treatment" workers. Although the risks were due to past exposure, case histories and recent acute effects indicate a present carcinogenic hazard in some Lombardy electroplating factories.

Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC).

OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.

Human health risk in relation to air quality in two municipalities in an industrialized area of Northern Italy.

Air quality is one of the major environmental issues related to human health, and people and authorities are increasingly aware and concerned about it, asking to be involved in decisions whose fallout can have consequences on their health. The objectives of the present study were to provide quantitative data on the impact of air pollution on the health of people living in two small municipalities in a highly industrialized, densely populated area of Northern Italy. We applied the approach proposed by the World Health Organization (WHO) using the AirQ 2.2.3 software developed by the WHO European Centre for Environment and Health, Bilthoven Division. Daily concentrations of ozone, nitrogen dioxide, and particulate matter of aerodynamic diameter≤10 µm (PM10) and ≤2.5 µm (PM2.5) were used to assess human exposure and health effects in terms of attributable proportion of the health outcome, annual number of excess cases of mortality for all causes, and cardiovascular and respiratory diseases. Long-term effects were estimated for PM2.5 as years of life lost. Considering short-term effects, PM2.5 had the highest health impact on the 24,000 inhabitants of the two small towns, causing an excess of total mortality of 8 out of 177 in a year. Ozone and nitrogen dioxide each caused about three excess cases of total mortality. Results on long-term effects showed, respectively, 433, 180, and 72 years of life lost for mortality for all causes, cardiopulmonary diseases and lung cancer, in a year. These results are consistent with other reports of the impact of air quality on human health and the AirQ software seems an effective and easy tool, helpful in decision-making.

What is Artificial about Life?

The announcement of "Artificial Life" by the Craig Venter group, and the media stir that arose from the news, provoked thoughts about the current technologies in contemporary science and the cultural tension of such projections on the media. The increasingly blurred boundaries between specialist and generalist media, while promising a wider appreciation of scientific discovery, potentially allow unrealistic, ideological claims to dictate scientific research. This is particularly evident in biology, where the pervading paradigm is still dominated by a physically naïve reductionism in which the only relevant causative layer is the molecular one. The reductionist hypothesis is that everything one observes is the result of an underlying molecular mechanism almost independent of the context in which it operates. Molecular mechanisms are often necessarily studied in isolation and therefore operate in unnatural conditions. The mechanistic view of biological regulation implies that we think of genes as intelligent agents. Here we try to critically analyze the motivations behind the spread of such unrealistic simplifications.

[From research on occupational tumors to interventional prevention: use of the OCCAM method at the ASL in Como]. / Dalla ricerca dei casi di tumore professionale agli interventi di prevenzione: l'utilizzo del metodo OCCAM nell'ASL di Como.

In the framework of "Occupational Cancers" project of the Lombardy Region, estimates of cancer risk by site and by economic activity for the incidence period 2001-2004 have been produced in the Local Health Unit of Como. Using these estimates a set of cancer cases with possible occupational origin has been determined. This has been carried out using the OCCAM approach, a case control study where incident cases are identified by hospital discharge records, controls are sampled from health population files and occupational histories are obtained by automatic link with social security archives. This has been integrated with the knowledge of firms and the workers' awareness of other cancer cases in the workforce of the same firms. Among 45 cases with potential occupational origin, 24 were established as due to occupation. These cases were referred for compensation. Moreover, carcinogenic risks still present in some firms were identified and appropriate interventions were carried out.

Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers.

We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality.

Confounders and confusion: Dealing with cancer cases of occupational origin.

BACKGROUND: The recognition of occupational cancers is often hampered by confusion between the individual determinants of the disease and effects at the group level. METHODS: Here we propose an approach, based on the evaluation of the attributable risk at the group level, that provides quantitative estimates of the roles of multiple causes in individuals affected of cancer within a population exposed to occupational risk. RESULTS: The estimate of individual probability can be easily obtained computing the attributable risk. This can be often achieved by using the existing information available in the literature. CONCLUSIONS: Dismissing the occupation as a cause of a cancer in an exposed subject on the sole basis of potential confounding is erroneous and should be withdrawn from medical practice.