Cancer risk in the siblings of individuals with major birth defects: a large Nordic population-based case-control study.

BACKGROUND: Individuals with major birth defects are at increased risk of developing cancer, indicating a common aetiology. However, whether the siblings of individuals with birth defects are also at an increased risk of cancer is unclear. METHODS: We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0-46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with odds ratios (OR) and 95% confidence intervals (CIs), using logistic regression models. RESULTS: In the total study population (aged 0-46 years), we observed no overall difference in cancer risk between individuals whose siblings had birth defects and those who had unaffected siblings (OR 1.02; 95% CI 0.97-1.08); however, the risk of lymphoid and haematopoietic malignancies was elevated (1.16; 1.05-1.28). The overall risk of childhood cancer (0-19 years) was increased for siblings of individuals who had birth defects (1.09; 1.00-1.19), which was mainly driven by lymphoma (1.35; 1.09-1.66), neuroblastoma (1.51; 1.11-2.05) and renal carcinoma (5.03; 1.73-14.6). The risk of cancer also increased with the number of siblings with birth defects (Ptrend = 0.008). CONCLUSION: Overall risk of cancer among individuals (aged 0-46 years) whose siblings had birth defects was not elevated, but the risk of childhood cancer (ages 0-19 years) was increased. Our novel findings are consistent with the common aetiologies of birth defects and cancer, such as shared genetic predisposition and environmental factors.

Validation of a full-shift benzene exposure empirical model developed for work on offshore petroleum installations on the Norwegian continental shelf.

Workers on offshore petroleum installations might be exposed to benzene, a carcinogenic agent. Recently, a full-shift benzene exposure model was developed based on personal measurements. This study aimed to validate this exposure model by using datasets not included in the model. The exposure model was validated against an internal dataset of measurements from offshore installations owned by the same company that provided data for the model, and an external dataset from installations owned by another company. We used Tobit regression to estimate GM (geometric mean) benzene exposure overall and for individual job groups. Bias, relative bias, precision, and correlation were estimated to evaluate the agreement between measured exposures and the levels predicted by the model. Overall, the model overestimated exposure when compared to the predicted exposure level to the internal dataset with a factor of 1.7, a relative bias of 73%, a precision of 0.6, a correlation coefficient of 0.72 (p = 0.019), while the Lin's Concordance Correlation Coefficient (CCC) was 0.53. The model underestimated exposure when compared to the external dataset with a factor of about 2, with a relative bias of -45%, a precision of 1.2, a correlation coefficient of 0.31 (p = 0.544), and a Lin's CCC of 0.25. The exposure model overestimated benzene exposure in the internal validation dataset, while the precision and the correlation between the measured and predicted exposure levels were high. Differences in measurement strategies could be one of the reasons for the discrepancy. The exposure model agreed less with the external dataset.

Sex differences in childhood cancer risk among children with major birth defects: a Nordic population-based nested case-control study.

BACKGROUND: Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. METHODS: We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0-19 years) and 218 980 matched population controls, born 1967-2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. RESULTS: Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6-12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8-2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6-3.1) than males (OR = 2.1, 95% CI = 1.9-2.2, Pinteraction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, PNIE <0.001), although more at younger ages (10% below years and 28% below 1 year). CONCLUSIONS: The birth defect-cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.

Benzene Exposure From Selected Work Tasks on Offshore Petroleum Installations on the Norwegian Continental Shelf, 2002-2018.

OBJECTIVES: Work on offshore petroleum installations may cause exposure to benzene. Benzene is a carcinogenic agent, and exposure among workers should be as low as reasonably practicable. We aimed to assess short-term (less than 60 min) benzene exposure from the most frequent work tasks on offshore installations on the Norwegian continental shelf and identify determinants of exposure. In addition, we aimed to assess the time trend in task-based benzene measurements from 2002 to 2018. METHODS: The study included 763 task-based measurements with a sampling duration of less than 60 min, collected on 28 offshore installations from 2002 to 2018. The measurements were categorized into 10 different tasks. Multilevel mixed-effect Tobit regression models were developed for two tasks: sampling and disassembling/assembling equipment. Benzene source, season, indoors or outdoors, design of process area, year of production start, sampling method, and work operation were considered as potential determinants for benzene exposure in the models. RESULTS: The overall geometric mean (GM) benzene exposure was 0.02 ppm (95% confidence intervals 95%(CI: 0.01-0.04). The pipeline inspection gauge (PIG) operation task was associated with the highest exposure, with a GM of 0.33 ppm, followed by work on flotation cells, disassembling/assembling, and sampling, with GMs of 0.16, 0.04, and 0.01 ppm, respectively. Significant determinants for the disassembling/assembling task were work operation (changing or recertifying valves, changing or cleaning filters, and breaking pipes) and benzene source. For sampling, the benzene source was a significant determinant. Overall, the task-based benzene exposure declined annually by 10.2% (CI 95%: -17.4 to -2.4%) from 2002 to 2018. CONCLUSIONS: The PIG operation task was associated with the highest exposure out of the ten tasks, followed by work on flotation cells and when performing disassembling/assembling of equipment. The exposure was associated with the type of benzene source that was worked on. Despite the decline in task-based exposure in 2002-2018, technical measures should still be considered in order to reduce the exposure.

Occupational Benzene Exposure in the Norwegian Offshore Petroleum Industry, 2002-2018.

PURPOSE: Workers on offshore petroleum installations are at risk of being exposed to benzene which is carcinogenic to humans. The present study aimed to assess the time trend of full-shift benzene exposure from 2002 to 2018 in order to characterize benzene exposure among laboratory technicians, mechanics, process operators, and industrial cleaners, and to examine the possible determinants of benzene exposure. METHODS: A total of 924 measurements of benzene exposure from the Norwegian petroleum offshore industry were included. The median sampling duration was 680 min, ranging from 60 to 940 min. The overall geometric mean (GM) and 95% confidence interval, time trends, and determinants of exposure were estimated using multilevel mixed-effects tobit regression analyses. Time trends were estimated for sampling duration below and above 8 h, both overall and for job groups. The variability of exposure between installation and workers was investigated in a subset of data containing worker identification. RESULTS: The overall GM of benzene exposure was 0.004 ppm. When adjusting for job group, design of process area, season, wind speed, and sampling duration, industrial cleaners had the highest exposure (GM = 0.012). Laboratory technicians, mechanics, and process operators had a GM exposure of 0.004, 0.003, and 0.004 ppm, respectively. Overall, the measured benzene exposure increased by 7.6% per year from 2002 to 2018. Mechanics had an annual increase of 8.6% and laboratory technicians had an annual decrease of 12.6% when including all measurements. When including only measurements above 8 h, mechanics had an increase of 16.8%. No statistically significant time trend was found for process operators. Open process area, high wind speed, and wintertime were associated with reduced exposure level. CONCLUSIONS: An overall increase in measured exposure was observed from 2002 to 2018. The increase may reflect changes in measurement strategy from mainly measuring on random days to days with expected exposure. However, the time trend varied between job groups and was different for sampling duration above or below 8 h. Industrial cleaners had the highest exposure of the four job groups while no differences in exposure were observed between laboratory technicians, mechanics, and process operators. The design of the process area, job group, wind speed, and season were all significant determinants of benzene exposure.

Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults.

OBJECTIVE: To examine associations between birth defects and cancer from birth into adulthood. DESIGN: Population based nested case-control study. SETTING: Nationwide health registries in Denmark, Finland, Norway, and Sweden. PARTICIPANTS: 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014. MAIN OUTCOME MEASURES: Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models. RESULTS: Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk. CONCLUSIONS: The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.