A cohort study of workers employed in a refractory brick plant

A mortality study was carried out on a cohort of workers who were exposed to silica dust in a refractory brick plant. The cohort was divided into two groups: workers with and without silicosis, and their mortality was contrasted with the death rate of Genova from 1960 to 1979. Results show an increased risk for laryngeal tumors (3 obs., 0.44 exp., SMR = 682), nonmalignant respiratory disease (16 obs., 3.2 exp., SMR = 500), and cardiovascular diseases (19 obs., 11 exp., SMR = 173) among silicotics. The mortality rate for lung cancer showed an increase for the cohort of workers as a whole (11 obs., 6 exp., SMR = 183). The almost double overall mortality observed in silicotic subjects raises some doubts about the validity of other proportional mortality studies that showed no excesses for workers in these industries.     

Lung cancer mortality among silicotic workers in Hong Kong--no evidence for a link.

BACKGROUND: The link between silica dust/silicosis and lung cancer is still very controversial. We examined the relationship between silica dust exposure and/or silicosis and lung cancer in a large cohort of silicotic workers in Hong Kong. PATIENTS AND METHODS: All workers with silicosis in Hong Kong diagnosed during the period 1981-1998 were followed up till the end of 1999 to ascertain their vital status and causes of death. Standardized mortality ratio (SMR) for lung cancer and other major causes of death were calculated. Axelson's indirect method was used to adjust for smoking effect. Multiple Cox regression models were carried out to examine the exposure-response relationship between silica dust and lung cancer. RESULTS: About 10% (86) of all 853 deaths were from lung cancer, giving a SMR of 1.69 [95% confidence interval (CI) 1.35-2.09]. Lung cancer SMR for caisson and surface construction workers were 2.39 (95% CI 1.50-3.62) and 1.61 (95% CI 1.21-2.10), respectively, which became 1.56 (95% CI 0.98-2.36) and 1.09 (95% CI 0.82-1.42) after adjusting for smoking. No consistent exposure-response relationship was detected between silica dust or severity of silicosis and lung cancer death. CONCLUSION: Our cohort study did not offer positive support to a link between silica or silicosis and lung cancer.     

Further evidence for a link between silica dust and esophageal cancer

Our objective was to examine the relationship between silicosis and esophageal cancer in Hong Kong. The mortality of esophageal cancer was investigated among caisson and non-caisson workers in a cohort of 2,789 male silicotic workers in Hong Kong during the period 1981-99. The standardized mortality ratio (SMR) was calculated using the Hong Kong general population rates as reference. The indirect method proposed by Axelson was used to adjust for the confounding effects of cigarette smoking and alcohol drinking. The SMR of esophageal cancer in the entire cohort was 2.22 (95% CI 1.36-3.43, based on 20 deaths) and was 4.21 (95% CI 1.81-8.30, based on 8 deaths) in the subgroup of caisson workers who had a higher exposure to silica dust. The relative risk of esophageal cancer for caisson silicotics was reduced to 2.34 after adjusting for the effects of smoking and alcohol drinking. No more excess risk of esophageal cancer was observed among non-caisson silicotic workers after the adjustments. This historical cohort study revealed that there was an increased mortality risk of esophageal cancer among silicotics who had worked in underground caissons in Hong Kong after adjusting for cigarette smoking and alcohol drinking. We believe that the excess risk of esophageal cancer mortality among caisson workers with silicosis could best be explained by the very heavy exposure to free silica dust in their working environment.     

Tobacco smoking and cancer: a meta-analysis

We conducted a systematic meta-analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case-control studies, 75 cohorts and 2 nested case-control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for 'current' and/or 'former' smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73-12.11), laryngeal (RR = 6.98; 95% CI: 3.14-15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86-15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63-4.84) and oral (RR = 3.43; 95% CI: 2.37-4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies.     

A case-referent study on lung cancer mortality among ceramic workers

A case-referent study has been carried out to test the hypothesis that silica-exposed ceramic workers have an increased risk of lung cancer. Next-of-kin interviews were conducted for 72 lung cancer cases and 319 referents, all deceased, to collect work histories and smoking habits. The diagnosis of silicosis was ascertained by checking the individual files of cases of silicosis where compensation had been received. It was found that, after controlling for age, period of death and smoking, workers in the ceramic industry had a higher lung cancer risk than those in other occupations in which there was no exposure to silica (Mantel-Haenszel rate ratio = 2.0; 95% confidence interval (CI) = 1.1-3.5). This increased risk was mainly due to a rate ratio of 3.9 (95% CI = 1.8-8.3) for silicotic individuals, while for non-silicotic ceramic workers it was only 1.4 (95% CI = 0.7-2.8). Exposure to other carcinogens in the workplace seems not to play any role in the development of lung cancer. Furthermore, the data do not suggest an increased risk for silicotic non-smokers. The results of the study tend to confirm previous evidence of an excess risk among silicotic subjects and points to a possible etiological role of the silicotic process itself in lung cancer.     

Coffee consumption and risk of endometrial cancer: findings from a large up-to-date meta-analysis

Several epidemiological studies have examined the association between coffee drinking and risk of endometrial cancer. To provide a quantitative assessment of this association, we conducted a meta-analysis of observational studies published up to October 2011 through a search of MEDLINE and EMBASE databases and the reference lists of retrieved article. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. A total of 16 studies (10 case-control and six cohort studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta-analysis. The pooled RR of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71 (95% CI: 0.62-0.81; p for heterogeneity = 0.13). By study design, the pooled RRs were 0.69 (95% CI: 0.55-0.87) for case-control studies and 0.70 (95% CI: 0.61-0.80) for cohort studies. By geographic region, the inverse association was stronger for three Japanese studies (pooled RR = 0.40; 95% CI: 0.25-0.63) than five studies from USA/Canada (pooled RR = 0.69; 95% CI: 0.60-0.79) or eight studies from Europe (pooled RR = 0.79; 95% CI: 0.63-0.99). An increment of one cup per day of coffee intake conferred a pooled RR of 0.92 (95% CI: 0.90-0.95). In conclusion, our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case-control studies. More large studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk.     

Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: a meta-analysis of epidemiologic studies.

The present meta-analysis was conducted to evaluate the strength and the consistency of the association between hepatitis C virus (HCV) infection and non-Hodgkin lymphoma (NHL) and other lymphoid neoplasms. Only studies with >or=100 cases which were also adjusted for sex and age were included. Fifteen case-control studies and three prospective studies contributed to present analysis, nine of which had not been included in previous meta-analyses. We calculated the pooled relative risks (RR) with corresponding 95% confidence intervals (95% CI), as a weighted average of the estimated RRs by random-effect models. The pooled RR of all NHL among HCV-positive individuals was 2.5 (95% CI, 2.1-3.0), but substantial heterogeneity was found between studies and by study design. Pooled RRs were 2.5 (95% CI, 2.1-3.1) in case-control studies and 2.0 (95% CI, 1.8-2.2) in cohort ones. The strongest source of heterogeneity seemed to be the prevalence of HCV among NHL-free study subjects (RR for NHL among HCV-positive individuals 3.0 and 1.9, respectively, for >or=5% and <5% HCV prevalence). RRs were consistently increased for all major B-NHL subtypes, T-NHL, and primary sites of NHL presentation. Thus, previous suggestions that the RRs for HCV differed by NHL subtype were not confirmed in our meta-analysis. Associations weaker than with NHL were found between HCV infection and Hodgkin's lymphoma (RR, 1.5; 95% CI, 1.0-2.1) and multiple myeloma (RR, 1.6; 95% CI, 0.7-3.6), but they were based on much fewer studies than NHL. The etiologic fraction of NHL attributable to HCV varies greatly by country, and may be upward of 10% in areas where HCV prevalence is high.     

2型糖尿病患者罹患生殖系统恶性肿瘤危险性的Meta分析

[目的]探讨2型糖尿病与生殖系统恶性肿瘤发生风险的关系。[方法]检索1979年1月至2012年10月Medline、Embase和Web of Science数据库公开发表的有关2型糖尿病与生殖系统恶性肿瘤关系的队列研究文献,按纳入和排除标准进行筛选,利用R软件及其Meta程序包对检索结果进行综合分析。[结果]共纳入39篇文献,包括10778543名观察对象。与非糖尿病人群相比,2型糖尿病患者发生生殖系统恶性肿瘤的合并相对危险度（RR）为1．15（95％CI：1．03～1．28）。2型糖尿病与女性生殖系统恶性肿瘤发生的相对危险度RR为l-39f95％CI：1．23－1．57）。2型糖尿病可以增加子宫内膜癌、宫颈癌和女性乳腺癌的发病风险,合并RR分别为1．83（95％CI：1．58-2．12）、2．13（95％CI：1．86－2．43）和1．16f95％CI：1．03-1.32）。卵巢癌风险的增加接近临界（RR=I．21,95％CI：0．99～1．48）;与前列腺癌的发病风险无关（RR=0．92,95％CI：0．78～1．09）。亚组分析提示,在欧美人群中2型糖尿病患者发生前列腺癌的风险降低．RR为0．80（95％CI：0．74－0．87）。[结论]2型糖尿病可能是子宫内膜癌、宫颈癌、乳腺癌的危险因素之一,可能是欧美人群前列腺癌保护因素。     

Bladder Cancer Risk in Painters: a Review of the Epidemiological Evidence, 1989–2004*

Epidemiological studies on the potential association between painting and the risk of bladder cancer published after the Monograph of the International Agency for Research on Cancer N. 47 of 1989 have been systematically reviewed. These included four cohort studies on the incidence of bladder cancer among painters, with a pooled relative risk (RR) of 1.10 (95% confidence interval, CI, 1.03–1.18), based on 893 cases observed. The corresponding summary RR from four cohort studies on mortality was 1.23 (95% CI 1.11–1.37), based on 370 deaths. The pooled RR from 14 case-control studies and a pooled-analysis of other 11 case-control studies was 1.35 (95% CI 1.19–1.53), based on 465 cases exposed. Overall, the RR from all epidemiological studies was 1.17 (95% 1.11–1.27). Thus, recent epidemiological evidence indicates a moderate excess risk for bladder cancer in painters. Some studies, however, suggested that any such risk would have been greater for exposures in the distant past. Open issues for interpretation include residual confounding by social class and tobacco smoking, and understanding the time-risk relation. In particular, the potential residual risk related to exposure over the last two to three decades remains to be defined. Financial support: This work was conducted with the contribution of the Italian Association for Cancer Research, the Italian League Against Cancer, and an unconditional support from FIAT Auto S.P.A.     

Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis

A meta-analysis was carried out to calculate a pooled estimate of relative risk of lung cancer following exposure to environmental tobacco smoke (ETS) and to determine whether there was any heterogeneity in the pooled estimates according to selected characteristics of the studies. A total of 35 case-control and five cohort studies providing quantitative estimates of the association between lung cancer and exposure to ETS published between January 1981 and March 1999 were identified. Using fixed- and random-effects models, we calculated pooled estimates of relative risk for exposure to ETS from subjects' parents (during childhood), spouses, and coworkers. As well, we investigated whether the pooled estimates of relative risk varied by study location, degree of control of potential confounding variables, proportion of cases confirmed histologically, proportion of surrogate respondents, nonresponse rates, and year of publication. The relative risk of lung cancer among non smoking women ever exposed to ETS from their husbands' smoking was 1.20 (95% confidence interval (CI): 1.12-1.29). The pooled relative risk was 1.19 (95% CI: 1.10-1.29) for case-control studies and 1.29 (95% CI: 1.04-1.62) for cohort studies. In various subgroup and meta-regression analyses, we found no statistically significant differences by selected characteristics of the studies. In addition, we found that the risk of lung cancer increased consistently with increasing levels of exposure. The 11 studies reporting relative risks among male non smokers yielded a pooled relative risk of 1.48 (95% CI: 1.13-1.92) for ever exposed to ETS, and the relative risk of lung cancer for ever being exposed to ETS at work was a 1.16 (95% CI: 1.05-1.28). These results are consistent with the hypothesis that exposure to ETS increases the risk of lung cancer. While there may be alternative explanations to the data, it is more likely that the observed association is not an artifact and that ETS causes lung cancer in non smokers.     

The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies.

PURPOSE: To determine whether intake of tomato products reduces the risk of prostate cancer using a meta-analysis. METHODS: We systematically searched MEDLINE and EMBASE and contacted authors to identify potential studies. Log relative risks (RRs) were weighed by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). Logistic regression and Poisson regression analyses were used to determine the effect produced by a daily intake of one serving of tomato product. RESULTS: Eleven case-control studies and 10 cohort studies or nested case-control studies presented data on the use of tomato, tomato products, or lycopene and met our inclusion criteria. Compared with nonfrequent users of tomato products (1st quartile of intake), the RR of prostate cancer among consumers of high amounts of raw tomato (5th quintile of intake) was 0.89 (95% CI 0.80-1.00). For high intake of cooked tomato products, this RR was 0.81 (95% CI 0.71-0.92). The RR of prostate cancer related to an intake of one serving/day of raw tomato (200 g) was 0.97 (95% CI 0.85-1.10) for the case-control studies and 0.78 (95% CI 0.66-0.92) for cohort studies. CONCLUSIONS: Our results show that tomato products may play a role in the prevention of prostate cancer. However, this effect is modest and restricted to high amounts of tomato intake. Further research is needed to determine the type and quantity of tomato products with respect to their role in preventing prostate cancer.     

Association between Smokeless Tobacco Use and Waterpipe Smoking and the Risk of Lung Cancer: A Systematic Review and Meta-Analysis of Current Epidemiological Evidence

Background: Smokeless tobacco and waterpipes are used by hundreds of millions of people worldwide and consumption rates exceed that of cigarette smoking in much of South East Asia and parts of the Middle East. However, the cancer risks of these methods of tobacco consumption are less well-characterized than those of cigarette smoking. The objective of this study was to systematically review the epidemiological evidence on the association between smokeless tobacco use and waterpipe smoking and lung cancer risk. Methods: The MEDLINE, EMBASE, Web of Science and OpenSIGLE databases were searched to identify eligible case-control and cohort studies (published before 1st December 2020 in any language) that adjusted for cigarette smoking or included non-cigarette smokers only. Summary odds ratio/relative risk estimates and confidence intervals were extracted, and pooled risk ratios (RRs) for lung cancer were calculated using random effects meta-analysis. Results: The literature search identified 2,465 publications: of these, 26 studies including 6,903 lung cancer patients were included in the synthesis (20 studies of smokeless tobacco use, five of waterpipe smoking, one of both). Our results suggest that smokeless tobacco use is associated with an increased risk of lung cancer among non-cigarette smokers, and that betel quid tobacco may be particularly hazardous. The random effects meta-analysis showed that exclusive use of any type of smokeless tobacco (pooled RR = 1.53, 95%CI 1.09 – 2.14), betel quid chewing (pooled RR = 1.77, 95%CI 1.06 – 2.95), and waterpipe smoking (pooled RR = 3.25, 95%CI 2.01 – 5.25) were significantly associated with an increased risk of lung cancer. Conclusions: This meta-analysis of case-control/cohort studies supports the hypothesis that use of smokeless tobacco and waterpipe smoking is associated with increased risk of developing lung cancer. Considering the widespread and increasing use of smokeless tobacco in developing countries, and increasing prevalence of waterpipe smoking in almost all societies, these findings inform formulation of public health policy, legislation and tobacco control measures at national and international level to increase awareness and decrease the prevalence of smokeless tobacco use and waterpipe smoking.     

Breastfeeding and Ovarian Cancer Risk: a Systematic Review and Meta-analysis of 40 Epidemiological Studies

The present systematic review and meta-analysis was conducted to assess any association between breastfeeding and the risk of ovarian cancer. A systematic search of published studies was performed in PUBMED and EMBASE and by reviewing reference lists from retrieved articles through March 2013. Data extraction was conducted independently by two authors. Pooled relative risk ratios were calculated using random-effect models. Totals of 5 cohort studies and 35 case-control studies including 17,139 women with ovarian cancer showed a30% reduced risk of ovarian cancer when comparing the women who had breastfed with those who had never breastfed (pooled RR = 0.70, 95% CI: 0.64-0.76; p = 0.00), with significant heterogeneity in the studies (p = 0.00;I2 = 76.29%). A significant decreasd in risk of epithelial ovarian cancer was also observed (pooled RR = 0.68, 95% CI: 0.61-0.76). When the participants were restricted to only parous women, there was a slightly attenuated but still significant risk reduction of ovarian cancer (pooled RR = 0.76, 95% CI: 0.69-0.83). For total breastfeeding duration, the pooled RRs in the < 6 months, 6-12 months and > 12 months of breastfeeding subgroups were 0.85 (95% CI: 0.77-0.93), 0.73 (95% CI: 0.65-0.82) and 0.64 (95%CI: 0.56-0.73), respectively. Meta-regressionof total breastfeeding duration indicated an increasing linear trend of risk reduction of ovarian cancer with the increasing total breastfeeding duration (p = 0.00). Breastfeeding was inversely associated with the risk of ovarian cancer, especially long-term breastfeeding duration that demonstrated a stronger protective effect.     

Silica: A lung carcinogen

Silica has been known to cause silicosis for centuries, and evidence that silica causes lung cancer has accumulated over the last several decades. This article highlights 3 important developments in understanding the health effects of silica and preventing illness and death from silica exposure at work. First, recent epidemiologic studies have provided new information about silica and lung cancer. This includes detailed exposure‐response data, thereby enabling the quantitative risk assessment needed for regulation. New studies have also shown that excess lung mortality occurs in silica‐exposed workers who do not have silicosis and who do not smoke. Second, the US Occupational Safety and Health Administration has recently proposed a new rule lowering the permissible occupational limit for silica. There are approximately 2 million US workers currently exposed to silica. Risk assessments estimate that lowering occupational exposure limits from the current to the proposed standard will reduce silicosis and lung cancer mortality to approximately one‐half of the rates predicted under the current standard. Third, low‐dose computed tomography scanning has now been proven to be an effective screening method for lung cancer. For clinicians, asking about occupational history to determine if silica exposure has occurred is recommended. If such exposure has occurred, extra attention might be given to the early detection of silicosis and lung cancer, as well as extra emphasis on quitting smoking. CA Cancer J Clin 2014;64:63–69. ^© 2013 American Cancer Society, Inc.     

Parity and risk of lung cancer in women: systematic review and meta-analysis of epidemiological studies

Multiple studies have assessed parity as a risk factor for lung cancer but results have been inconclusive. We searched MEDLINE (through August 2010) and the Institute of Scientific Information Web of Knowledge database (through April 2011) to identify studies investigating the association of parity with lung cancer and allowing the calculation of dose-response trends using a linear model. Between-study heterogeneity was assessed using Cochran's Q statistic and the I(2) index. Summary per-child relative risks (RRs) with their 95% confidence interval (CI) were estimated using random effects meta-analysis. Sixteen eligible studies (8077 lung cancer patients; 350,295 unaffected individuals) provided data for meta-analysis. There was significant between-study heterogeneity (p<0.001; I(2)=73%). The summary per livebirth RR was 0.98 (95% CI, 0.95-1.02), indicating no effect of parity on lung cancer risk. Results were consistent in case-control (n=11), RR=0.99 (95% CI, 0.94-1.04), and cohort studies (n=5), RR=0.97 (95% CI, 0.92-1.03). Studies not including small-cell lung cancer patients found a borderline protective effect of parity, RR=0.94 (95% CI, 0.88-1.00). In contrast, no effect was observed in studies including small-cell lung cancer patients, RR=1.00 (95% CI, 0.98-1.03); p for difference=0.05. Overall, there was little evidence of a dose-response relationship between increasing number of livebirths and lung cancer; however, studies have produced heterogeneous results. Future studies should include analyses in well-defined histological disease subgroups.     

Dietary total fat and fatty acids intake,serum fatty acids and risk of breast cancer: A meta‐analysis of prospective cohort studies

Results from prospective cohort studies on the association between dietary total fat and fatty acids intake and risk of breast cancer remain controversial. Pertinent prospective cohort studies were identified by a search of Embase and PubMed from inception to September 2015. Study‐specific relative risks (RRs) with 95% confidence intervals were pooled using a random‐effect model. Between‐study heterogeneity and publication bias were assessed, and sensitivity analysis was conducted. Twenty‐four independent studies on dietary total fat and fatty acids intake and seven studies on serum fatty acids were included. The pooled RR of breast cancer for the highest vs. lowest category of dietary total fat intake was 1.10 (1.02–1.19); however, no association was observed in studies adjusting for traditional risk factors of breast cancer. No association was observed between animal fat, vegetable fat, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n‐3 PUFA, n‐6 PUFA, eicosapentaenoic acid, docosahexaenoic acid, alpha‐linolenic acid, oleic acid, linoleic acid and arachidonic acid and risk of breast cancer. The pooled RRs of breast cancer for the highest vs. lowest category of serum SFA, MUFA, PUFA, n‐3 PUFA and n‐6 PUFA were 1.00 (0.78–1.28), 1.41 (0.99–2.03), 0.59 (0.27–1.30), 0.81 (0.60–1.10) and 0.84 (0.60–1.18), respectively. Results from this meta‐analysis suggested that dietary total fat and fatty acids might be not associated with risk of breast cancer.     

Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies.

Intervention trials with supplemental beta-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7-16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. beta-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87-1.11; highest versus lowest quintile). The RRs for alpha-carotene, lutein/zeaxanthin, and lycopene were also close to unity. beta-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67-0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in beta-cryptoxanthin, such as citrus fruit, may modestly lower the risk.     

Pooled exposure–response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study

Objectives: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure–response data. We have conducted a pooled exposure–response analysis of 10 silica-exposed cohorts to investigate lung cancer. Methods: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m³) across cohorts. Results: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0, 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m³ respirable crystalline silica (the permissible level in many countries) was 1.1–1.7%, above background risks of 3–6%. Conclusions: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure–response analysis and risk assessment for silica using data from multiple studies.     

Preventable exposures associated with human cancers

Information on the causes of cancer at specific sites is important to cancer control planners, cancer researchers, cancer patients, and the general public. The International Agency for Research on Cancer (IARC) Monograph series, which has classified human carcinogens for more than 40 years, recently completed a review to provide up-to-date information on the cancer sites associated with more than 100 carcinogenic agents. Based on IARC's review, we listed the cancer sites associated with each agent and then rearranged this information to list the known and suspected causes of cancer at each site. We also summarized the rationale for classifications that were based on mechanistic data. This information, based on the forthcoming IARC Monographs Volume 100, offers insights into the current state-of-the-science of carcinogen identification. Use of mechanistic data to identify carcinogens is increasing, and epidemiological research is identifying additional carcinogens and cancer sites or confirming carcinogenic potential under conditions of lower exposure. Nevertheless, some common human cancers still have few (or no) identified causal agents.