Selenium and cancer risk: Wide-angled Mendelian randomization analysis.

Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site-specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2 < .3) were used as instrumental variables. Genetic associations of selenium-associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P < .1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse-variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site-specific cancers or any cancer (all 22 site-specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one-unit increase in log-transformed levels: 0.83; 95% confidence interval [CI]: 0.67-1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02-1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69-1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well-powered studies.

Statin use and risk of multiple myeloma: An analysis from the cancer research network.

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N = 2,532). For each case, five controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (≥6 cumulative months) and risk of multiple myeloma, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.

Increased risk of acute myelogenous leukemia and multiple myeloma in a historical cohort of upstream petroleum workers exposed to crude oil.

Benzene exposure has been shown to be related to acute myelogenous leukemia, while the association with multiple myeloma and non-Hodgkin lymphoma has been a much-debated issue. We performed a historical cohort study to investigate whether workers employed in Norway's upstream petroleum industry exposed to crude oil and other products containing benzene have an increased risk of developing various subtypes of hematologic neoplasms. Using the Norwegian Registry of Employers and Employees we included all 27,919 offshore workers registered from 1981 to 2003 and 366,114 referents from the general working population matched by gender, age, and community of residence. The cohort was linked to the Cancer Registry of Norway. Workers in the job category "upstream operator offshore", having the most extensive contact with crude oil, had an excess risk of hematologic neoplasms (blood and bone marrow) (rate ratio (RR) 1.90, 95% confidence interval (95% CI): 1.19-3.02). This was ascribed to an increased risk of acute myelogenous leukemia (RR 2.89, 95% CI: 1.25-6.67) and multiple myeloma (RR 2.49, 95% CI: 1.21-5.13). There were no statistical differences between the groups in respect to non-Hodgkin lymphoma. The results suggest that benzene exposure, which most probably caused the increased risk of acute myelogenous leukemia, also resulted in an increased risk of multiple myeloma.

An analysis of the risk of B-lymphocyte malignancies in industrial cohorts.

Among numerous studies of occupational groups with varied chemical exposures (e.g., farmers, petroleum workers, and rubber workers), some have reported excess risk for non-Hodgkin's lymphoma (NHL), multiple myeloma, and other cancers of the B-lymphocyte cell line. While not conclusive, these studies raise questions about the effects of chemical exposures on the lymphocytic versus myeloid cell lines. Almost 70 occupational cohort studies were identified that addressed B-cell cancer risks in 9 major industrial categories, in order to look for common patterns across industries. This effort was substantially limited by the inconsistent nature of lymphohematopoietic (LH) classification schemes across studies and over time, and the relative paucity of B-cell-specific results in studies for any given industry. Taking these limitations into consideration, a descriptive, graphical analysis suggested a pattern of B-cell cancer elevations in the rubber and "general chemical" industries, but no consistent patterns in petroleum production/distribution or petrochemical production. The limited data sources, which lack detail about differences in hazard and exposure for different types of products/chemicals, did not allow a comprehensive look at possible common exposures associated with B-cell cancer elevations across industries. This study suggests that evaluation of possible associations between specific chemical exposures and B-cell malignancies would require additional studies with clear and common definitions of B-cell outcomes. The article concludes by giving an example of a possible common framework for categorizing NHL, the diseases for which most classification issues arise.

Multiple myeloma and benzene exposure in a multinational cohort of more than 250,000 petroleum workers.

Case reports have suggested an association between benzene exposure and multiple myeloma. Because petroleum workers are exposed to benzene or benzene-containing liquids, studies of these workers provide an opportunity for investigating the relationship between benzene and multiple myeloma. A large number of cohort studies of petroleum workers have been conducted. However, few of them have reported results of multiple myeloma separately. One reason is that multiple myeloma is usually grouped with other lymphopoietic cancers in the analysis. Another reason is that multiple myeloma is relatively rare, and few individual studies are large enough to provide reliable risk estimates. To determine the risk of multiple myeloma in petroleum (refinery, distribution, production, and pipeline) workers, we have identified 22 cohort mortality studies of petroleum workers in the United States, the United Kingdom, Canada, and Australia. Authors of these studies were contacted, and data on the number of observed deaths and age-specific person-years of observation were requested. Data from individual studies were combined in a pooled analysis (meta-analysis). In addition to the pooled analyses, results for individual cohorts, most of which have never been reported before, are also presented. The combined multinational cohort consisted of more than 250,000 petroleum workers, and the observation period covered an interval of 55 years from 1937 to 1991. A total of 205 deaths from multiple myeloma were observed, compared to 220.93 expected, a total derived from respective national mortality rates. The corresponding standardized mortality ratio (SMR) was 0.93 and the 95% confidence interval (95% CI) was 0.81-1.07. Additional analyses were performed by type of facility and industrial process. Stratum-specific SMRs (95% CIs) were 0.92 (0.77-1.09) for refinery workers and 0.93 (0.69-1.23) for distribution workers. When individual cohorts were stratified by length of observation, no pattern was detected. The pooled analysis indicates that petroleum workers are not at an increased risk of multiple myeloma as a result of their exposure to benzene, benzene-containing liquids, or other petroleum products in their work environment. This conclusion is supported by cohort studies of workers in other industries who were exposed to benzene as well as by population-based case-control studies of multiple myeloma and occupational exposures.

Does benzene cause multiple myeloma? An analysis of the published case-control literature.

Two case series and two epidemiological studies in the 1970s and 1980s suggested that benzene exposure might be a risk factor for multiple myeloma. An analysis has now been conducted of the published population-based and hospital-based case-control studies published through mid-1995 that permit examination of the relationship between multiple myeloma and benzene exposure or surrogates for benzene exposure. No increased association was found between multiple myeloma and benzene exposure or exposure to chemical groups that included benzene. The odds ratios from these analyses approximated 1.0. Exposures to petroleum products and employment in petroleum-related occupations did not appear to be risk factors for multiple myeloma. Cigarette smoking, as a surrogate of benzene exposure, was not found to be associated with myeloma, while some studies of products of combustion described as "engine exhaust" did show a significant association with multiple myeloma. In toto, the population-based and hospital-based case-control literature indicated that benzene exposure was not a likely causal factor for multiple myeloma.

Lymphohaematopoietic malignancies and quantitative estimates of exposure to benzene in Canadian petroleum distribution workers.

OBJECTIVE: To evaluate the relation between mortality from lymphohaematopoietic cancer and long term, low level exposures to benzene among male petroleum distribution workers. METHODS: This nested case control study identified all fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkin's lymphoma. A four to one matching ratio was used to select a stratified sample of controls from the same cohort, controlling for year of birth and time at risk. Industrial hygienists estimated workplace exposures for benzene and total hydrocarbons, without knowledge of case or control status, for combinations of job, location, and era represented in all work histories. Average daily benzene concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs. Company medical records were used to abstract information on other potential confounders such as cigarette smoking, although the data were incomplete. Odds ratios (ORs) were calculated with conditional logistic regression techniques for several exposure variables. RESULTS: Risks of leukaemia, non-Hodgkin's lymphoma, and multiple myeloma were not associated with increasing cumulative exposure to benzene or total hydrocarbons. For leukaemia, the logistic regression model predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene. Duration of exposure to benzene was more closely associated with risk of leukaemia than other exposure variables. It was not possible to completely control for other risk factors, although there was suggestive evidence that smoking and a family history of cancer may have played a part in the risk of leukaemia. CONCLUSION: This study did not show a relation between lymphohaematopoietic cancer and long term, low level exposures to benzene. The power of the study to detect low-such as twofold-risks was limited. Thus, further study on exposures to benzene in this concentration range are warranted.

Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up.

Using computerized pharmacy records from 1969 to 1973 for a cohort of 143,574 members of the Kaiser Permanente Medical Care Program, we have been testing associations of 215 drugs or drug groups with subsequent incidence of cancer at 56 sites. This paper presents findings with follow-up through 1984. There were 227 statistically significant (P less than 0.05, two-tailed) associations: 170 positive, 57 negative. Some were undoubtedly chance findings; others were likely due to confounding by unmeasured covariables. However, several associations suggested hypotheses for further studies and/or the need for continued observation. Most notable among findings not previously reported were associations of several antibiotics, both oral and topical, with lung cancer. These associations could not be explained by indications for drug use or by differences in smoking habits between users and nonusers, and suggest a possible link between the occurrence of bacterial infections and risk for cancer. In general, our results continue to suggest that most medications used during that period did not affect cancer incidence substantially. However, for less frequently prescribed medications, our power to detect moderate increases in cancer risk was quite low.