Relative Risk Of Lung Cancer Research Articles

Risk of lung cancer from exposure to dusts and fibers in Leningrad Province, Russia

Exposures to several dusts and fibers (DFs) have been established or suggested as etiologic factors for lung cancer. To investigate lung cancer risk in relation to exposure to DFs, we identified 540 pathologically-diagnosed lung cancer cases and 582 controls from the 1993-1998 autopsy records of the 88 hospitals of Leningrad Province, Russia. Lifetime job-specific exposure measurements were available for 15 organic, 15 man-made and 28 natural-inorganic agents. In male workers, increased risks were found for linen dust (OR = 3.68, 95% CI 1.00-13.6, adjusted for age, smoking and residence), and unspecified DFs (OR = 1.44, 95% CI 1.07-1.94). Small non-significant excess risks were observed for quartz dust (OR = 1.27; 95% CI 0.83-1.93) and man-made vitreous fibers (MMVFs) (OR = 1.82, 95% CI 0.88-3.75). In female subjects, risks were non-significantly associated with paper dust (OR = 1.77, 95% CI 0.74-4.20), and unspecified DFs (OR = 1.52, 95% CI 0.77-3.03). The study showed increased lung cancer risk for selected categories of DFs.

Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies.

BackgroundGlutathione S-transferases (GSTs) are known to abolish or reduce the activities of intracellular enzymes that help detoxify environmental carcinogens, such as those found in tobacco smoke. It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results. Methods and FindingsLiterature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of five GST polymorphisms ( GSTM1 null, GSTT1 null, I105V, and A114V polymorphisms in the GSTP1 genes, and GSTM3 intron 6 polymorphism) available before August, 2005, with investigation of potential sources of heterogeneity. Included in the present meta-analysis were 130 studies, involving a total of 23,452 lung cancer cases and 30,397 controls. In a combined analysis, the relative risks for lung cancer of the GSTM1 null and GSTT1 null polymorphisms were 1.18 (95% confidence interval [CI]: 1.14–1.23) and 1.09 (95% CI: 1.02–1.16), respectively, but in the larger studies they were only 1.04 (95% CI: 0.95–1.14) and 0.99 (95% CI: 0.86–1.11), respectively. In addition to size of study, ethnic background was a significant source of heterogeneity among studies of the GSTM1 null genotype, with possibly weaker associations in studies of individuals of European continental ancestry. Combined analyses of studies of the 105V, 114V, and GSTM3*B variants showed no significant overall associations with lung cancer, yielding per-allele relative risks of 1.04 (95% CI: 0.99–1.09), 1.15 (95% CI: 0.95–1.39), and 1.05 (95% CI: 0.89–1.23), respectively. ConclusionsThe risk of lung cancer is not strongly associated with the I105V and A114V polymorphisms in the GSTP1 gene or with GSTM3 intron 6 polymorphism. Given the non-significant associations in the larger studies, the relevance of the weakly positive overall associations with the GSTM1 null and the GSTT1 null polymorphisms is uncertain. As lung cancer has important environmental causes, understanding any genetic contribution to it in general populations will require the conduct of particularly large and comprehensive studies.

LUNG CANCER RISK AMONG FORMER URANIUM MINERS OF THE WISMUT COMPANY IN GERMANY

After 1946, the WISMUT Company developed the third-largest uranium-mining province in the world in the German Democratic Republic. A case-control study among former WISMUT miners was conducted to investigate the lung cancer risk in relation to attained age, time since exposure, exposure duration, and exposure rate. It consisted of 505 patients with lung cancer and 1,073 controls matched to cases according to the year of birth. The cumulative exposure to radon and radon decay products was calculated as the sum of yearly exposures and expressed in Working Level Months (WLM). Cases had a mean cumulative exposure of 552 WLM compared to 420 WLM in controls. There was a statistically significant increase in lung cancer risk for cumulative exposures above 800 WLM. Under the assumption of a linear risk model, there was a significant increase in the relative risk of 0.10 per 100 WLM after adjusting for smoking and asbestos exposure. For current smokers the increase in relative risk was lower (0.05 per 100 WLM), whereas it was higher (0.20 per 100 WLM) among nonsmokers and longtime ex-smokers. After correcting in a sensitivity analysis for the fact that the controls of this study had a higher average exposure than the population of WISMUT workers they were recruited from, the adjusted ERR increased to 0.24 per 100 WLM. Lung cancer risk declined with time since exposure, except for exposures received 45 or more years ago. No inverse dose rate effect was observed.

Expanding research on the economics of occupational health

Studies seeking direct estimates of the lung cancer risk associated with residential radon exposure lasting several decades have been conducted in many European countries. Individually these studies have not been large enough to assess moderate risks reliably. Therefore data from all 13 European studies of residential radon and lung cancer satisfying certain prespecified criteria have been brought together and analyzed.Data were available for 7148 persons with lung cancer and 14,208 controls, all with individual smoking histories and residential radon histories determined by long-term radon gas measurements.The excess relative risk of lung cancer per 100 Bq/m3 increase in the observed radon concentration was 0.08 [95% confidence interval (95% CI) 0.03-0.16; P=0.0007] after control for confounding. The dose-response relationship was linear with no evidence of a threshold, and it remained significant when only persons with observed radon concentrations of <200 Bq/m3 were included. There was no evidence that the excess relative risk varied with age, sex, or smoking history. Removing the bias induced by random uncertainties related to radon exposure assessment increased the excess relative risk of lung cancer to 0.16 (95% CI 0.05-0.31) per 100 Bq/m3. With this correction, estimated risks at 0, 100, and 400 Bq/m3, relative to lifelong nonsmokers with no radon exposure, were 1.0, 1.2, and 1.6 for lifelong nonsmokers and 25.8, 29.9, and 42.3 for continuing smokers of 15-24 cigarettes/day.These data provide firm evidence that residential radon acts as a cause of lung cancer in the general population. They provide a solid basis for the formulation of policies with which to manage risk from radon and reduce deaths from the most common fatal cancer in Europe.

Revisiting evidence on lung cancer and passive smoking: Adjustment for publication bias by means of “trim and fill” algorithm

Meta-analyses are subject to bias because smaller or non-significant studies are less likely to be published, and most meta-analyses do not consider the effect of publication bias on their results. To assess the true risk, we revisited a famous meta-analysis including 37 studies on lung cancer and passive smoking, and adjusted for publication bias by means of the "trim and fill" algorithm. The adjusted relative risk of lung cancer in non-smokers who lived with a smoker from the 44 studies including the 7 filled ones was 1.19 (95% confidence interval 1.08-1.31, p = 0.0004), and the estimate of excess risk fell from 24 to 19%.

Fine Particles and Mortality

period of the study. Even if proportionality of hazards were to hold for exposure to fine particles, we know that it most definitely does not hold for cigarette smoking, a strong risk factor and a potential confounder of the PM mortality association. For example, we know that, for a given daily level of smoking, the relative risk of lung cancer is strongly dependent on duration of smoking. Moreover, when smokers quit, the relative risk for mortality declines over a period of many years, and not virtually instantly as is assumed by proportional hazards. What influence does this manifestly incorrect model for a strong confounder have on the estimates of air pollution effects? Similarly the use of a proportional hazards model to adjust for age of entry into studies is also suspect.

Risk of cancer following partial gastrectomy for benign ulcer disease.

The relative risk of developing cancer after partial gastrectomy for benign ulcer disease, expressed as the standardized incidence ratio, was examined in a population-based cohort comprising 6459 patients operated on between 1950 and 1958. Follow-up to 1983 revealed 1112 patients with cancer versus 1128 expected cases (relative risk 1.0 (95 per cent confidence interval (c.i.) 0.9-1.1)). The overall risk increased over time; it was higher in younger than in older patients but was not related to sex, surgical procedure (Billroth I or II gastrectomy) or diagnosis at operation (duodenal or stomach ulcer). There was an increased risk for lung cancer (relative risk 1.5 (95 per cent c.i. 1.2-1.7)), for oesophageal cancer in patients operated on for stomach ulcer (relative risk 2.2 (95 per cent c.i. 1.0-4.2)) and for cancer of the biliary tract in men (relative risk 1.9 (95 per cent c.i. 1.2-2.9)) and in those operated on for duodenal ulcer (relative risk 1.7 (95 per cent c.i. 1.0-2.8)). The overall risk for genital cancer in women was unchanged but decreased with increasing duration of follow-up and age. Cancers of the nervous system occurred less frequently than expected (relative risk 0.5 (95 per cent c.i. 0.3-0.8)), while the risk for cancer of the buccal cavity, lymphatic and haematopoietic systems, pancreas, breast, prostate, kidney and bladder was unchanged.

Risk of Second Lung Cancer in Chronic Lymphocytic Leukemia.

Background: Studies have shown that patients with chronic lymphocytic leukemia (CLL) are at increased risk of developing second lung cancer. The underlying mechanisms for this increased risk have yet not been identified. Risk factors may differ between histological lung cancer subtypes. However, though relevant to the clarification of the association between the two malignancies, little is known about the lung cancer subtype distribution in CLL patients.Methods: We investigated the occurrence of second lung cancer overall and its major histological subtypes in all patients diagnosed with CLL in Denmark between 1943 and 1999 in a retrospective registry-based cohort study. The relative risk was expressed as the standardized incidence ratio (SIR), i.e. the ratio of the observed to the expected number of lung cancer cases, based on age-, sex-, and calendar year specific incidence rates for the Danish population, available from the Danish Cancer Registry.Results: Overall, 9,541 patients diagnosed with CLL between 1943 and 1999 were followed for lung cancer occurrence. The median age at onset was 70 years and the male-to-female ratio was 1.6. Second lung cancer occurred in 147 patients (122 men and 25 women) during 36,604 person-years of follow-up (median 2.5 years) corresponding to a statistically significantly increased relative risk (SIR=1.83, 95% CI 1.55–2.15). There was no difference in risk between women and men (phom=0.27). The relative risk for lung cancer varied slightly by age at CLL being particularly high in younger age groups (≤59 years SIR=2.18 (1.53–3.10), 60–69 years SIR=2.26 (1.78–2.86), 70–79 years SIR=1.28 (0.93–1.76), ≥80 years SIR=1.51 (0.79–2.90); phom=0.02). In contrast, SIR for lung cancer did not vary by time since CLL diagnosis (phom=0.64). In 95 cases (72 men, 23 women) of second lung cancer information about major histological subtypes were available. We found a statistically significantly elevated risk for all major subtypes, except small-cell carcinoma (adenocarcinoma SIR=2.85 (2.04–3.99), large-cell carcinoma SIR=2.31 (1.04–5.15), squamous cell carcinoma SIR=2.30 (1.68–3.14), small cell carcinoma SIR=1.47 (0.90–2.39)).Discussion: In one of the largest and most detailed register-based cohort studies so far, we found an increased occurrence of lung cancer among CLL patients, which was apparent for major lung cancer subtypes. While increased medical surveillance of the CLL patients cannot be ruled out as explanation for the increased risk, the uniform distribution over time since CLL diagnosis suggests that it is unrelated to initial therapy. Tobacco smoking is the major risk factor in lung cancer. Data on smoking history were not available in our study, however, previous studies suggest that smoking is not associated with CLL. Family aggregation found for both lung cancer and CLL may indicate hereditary predisposition to the two conditions. Furthermore, individual susceptibility to malignant diseases may be influenced by polymorphisms in enzymes metabolizing carcinogenes, suggested independently for CLL and lung cancer. Given the prolonged survival of patients with CLL, further studies are needed to address the causal relationship between CLL and second malignancies, including lung cancer.

Ionizing Radiation and Tobacco Use Increases the Risk of a Subsequent Lung Carcinoma in Women With Breast Cancer: Case-Only Design

To analyze the risk of lung cancer in women treated with radiotherapy for breast cancer. We accessed the lung dose in relation to different radiotherapy techniques, provided the excess relative risk (ERR) estimate for radiation-associated lung cancer, and evaluated the influence of tobacco use. The Swedish Cancer Registry was used to identify 182 women diagnosed with breast and subsequent lung cancers in Stockholm County during 1958 to 2000. Radiotherapy was administered to 116 patients. Radiation dose was estimated from the original treatment charts, and information on smoking history was searched for in case records and among relatives. The risk of lung cancer was assessed in a case-only approach, where each woman contributed a pair of lungs. The average mean lung dose to the ipsilateral lung was 17.2 Gy (range, 7.1 to 32.0 Gy). A significantly increased relative risk (RR) of a subsequent ipsilateral lung cancer was observed at > or = 10 years of follow-up (RR = 2.04; 95% CI, 1.24 to 3.36). Squamous cell carcinoma (RR = 4.00; 95% CI, 1.50 to 10.66) was the histopathologic subgroup most closely related to ionizing radiation. The effect of radiotherapy was restricted to smokers only (RR = 3.08; 95% CI, 1.61 to 5.91). The ERR/Gy for women with latency > or = 10 years after exposure was 0.11 (95% CI, 0.02 to 0.44). Radiotherapy for breast cancer significantly increases the risk of lung carcinoma more than 10 years after exposure in women who smoked at time of breast cancer.

Secondary Lung Tumors in Hematological Patients

Advances made in the field of chemotherapy and radiotherapy have considerably increased the survival of patients with Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL). Unfortunately, these antiblastic therapies have also increased the risk of late complications such as second tumors, especially second lung cancers. Although the role of ionizing radiations in carcinogenesis is now clear, less is known about the damage caused by chemotherapy, immunodeficiency induced by drugs or hematological pathologies, and cigarette smoking. In HD, the relative risk (RR) of second lung cancer increases considerably in relation to the dose of ionizing radiation given to the patient, with an RR of 9.6 when more than 9 Gy are administered. Some studies have reported a significantly higher risk of second lung cancers in smokers compared with nonsmokers ( p = .03). The role of chemotherapy in the development of second lung cancers has yet to be determined. Although some authors correlate a greater risk with an increased number of chemotherapy cycles, others maintain that chemotherapy increases the risk of second lung cancer only if associated with cigarette smoking. Even less is known about the correlation between NHL and second lung cancer. Although the RR is higher in long-term NHL survivors than in healthy individuals (RR = 1.36), the heterogeneity of histotype and treatment does not permit us to confirm a correlation with chemotherapy and smoking. Conversely, in CLL, the development of second lung cancer appears to be linked to the immunodeficiency that accompanies this hematological malignancy. This is confirmed by the identical RR (1.66) for CLL patients subjected to chemotherapy and for those who have only follow-up.

Lung cancer in Asian women—the environment and genes*

The mortality rate of lung cancer in Asian women has increased significantly in the past few decades. Environmental factors include tobacco smoke (active and environmental), other indoor pollutions (cooking oil vapours, coal burning, fungus spores), diet, and infections. Active tobacco smoking is not the major factor. The relative risk of lung cancer among non-smoking women ever exposed to environmental smoke from their husbands was 1.20 from a meta-analysis. Cooking oil vapours associated with high temperature wok cooking and indoor coal burning for heating and cooking in unvented homes, particularly in rural areas, are risk factors for Chinese women. Chronic benign respiratory diseases due to the fungus Microsporum canis probably accounts for the high incidence of lung cancer in northern Thai women at Sarapee. Diets rich in fruits, leafy green vegetables, and vitamin A are protective, while cured meat (Chinese sausage, pressed duck and cured pork), deep-fried cooking, and chili increased the risk. Tuberculosis is associated with lung cancer. Also, a Taiwanese study showed that the odds ratio of papillomavirus (HPV) 16/18 infection in non-smoking female lung cancer patients was 10.1, strongly suggesting a causative role. Genetic factors have also been studied in Chinese women, including human leucocyte antigens, K-ras oncogene activation, p53 mutation, polymorphisms of phase I activating enzymes (cytochrome P450, N-acetyltransferase slow acetylator status), and phase II detoxifying enzymes (glutathione-S-transferases, N-acetyltransferase rapid acetylator status). New molecular screening technology would facilitate identification of molecular targets for future studies. The interaction between environmental and genetic factors should also be further elucidated.

Smoking habit and genetic factors associated with lung cancer in a population highly exposed to arsenic

In order to find some relationship between genetic differences in metabolic activation and detoxification of environmental carcinogens and host susceptibility to chemically induced cancers, we have investigated the distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung cancer patients and healthy volunteers of the second region in the north of Chile highly exposed to arsenic. The main sources of environmental arsenic exposure in Chile are copper smelting and drinking water, specially in the second region, the most important copper mining region in the world that shows the highest lung cancer mortality rate in the country (35/100.00). The population of Antofagasta, the main city of the region was exposed between 1958 and 1970 to arsenic concentrations in drinking water of 860 μg/m 3, presently declining to 40 μg/m 3. For men the MspI CYP1A1 *2A genotype was associated with a highly significant estimated relative lung cancer risk (O.R. = 2.60), but not GSTM1 by itself. The relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habits (O.R. = 2.98). In the second region the cancer mortality rate for As associated cancers, might be related at least part to differences in As biotransformation. In this work we demonstrate that genetic biomarkers such as CYP1A1 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with higher risk for lung cancer, due to arsenic exposure.

Familial Lung Cancer and Aggregation of Smoking Habits: A Simulation of the Effect of Shared Environmental Factors on the Familial Risk of Cancer

Tobacco smoking is the principal cause of lung cancer. The risk of lung cancer in the offspring of lung cancer patients is about twice higher than the risk in the general population. The present study investigated the contribution of shared smoking habits to the familial clustering of lung cancer. We estimated the relative risk of lung cancer attributable to smoking according to the extent to which smokers transmit their smoking habits to the offspring (heritability of smoking), the prevalence of smoking in the general population, and the risk of lung cancer for smokers compared with nonsmokers. The relative risk of lung cancer for the offspring of lung cancer patients attributable to smoking was 1.19 when published data on smoking practice were modeled (i.e., assuming that the heritability of smoking was 0.5, the smoking prevalence 40%, and the odds ratio of lung cancer for smokers versus nonsmokers was 20). Most familial cases of lung cancer cannot be attributed to shared smoking habits. The example of smoking can be used for other familial cancers, for which no strong environmental risk factors are usually known, to infer the primary role for heritable genes.

Use of nonaspirin NSAIDs and risk of lung cancer

Epidemiologic evidence is conflicting regarding the potential for nonsteroidal antiinflammatory drugs (NSAIDs) to lower the risk of lung cancer. We thus determined the incidence of lung cancer among a cohort of over 242,000 adults in Denmark who had been issued NSAID prescriptions during 1991-2002 and calculated the relative risks of this cancer according to the numbers of prescriptions received. Similar analyses were conducted among a subset with chronic obstructive pulmonary disease, of whom the large majority was assumed to have been smokers, as an indirect control for smoking. Utilization of Danish registries ensured essentially complete and unbiased ascertainment of prescriptions and cancer outcomes. The relative risks of lung cancer among NSAID users redeeming 10 or more prescriptions vs. nonusers in the general population and among chronic obstructive pulmonary disease patients were 1.51 (95% CI = 1.33-1.71) and 1.55 (95% CI = 0.93-2.60) and tended to decline with decreasing numbers of NSAIDs prescribed. Separate analyses for adenocarcinoma and squamous cell carcinoma also failed to show reduced risks among NSAID users. Confounding by indication may have contributed to the increased risks, but the study provides no evidence to suggest that recent NSAID intake may be protective for lung cancer.

Tamoxifen does not reduce the risk of lung cancer in women

7212 Background: Mounting evidence indicates that women have a different susceptibility to lung cancer than men. In particular, female never-smokers are more likely than male never-smokers to develop lung cancer. Moreover, women are more likely to be diagnosed with adenocarcinoma than are men. Coupled with the localization of estrogen receptors alpha and beta to lung cancer cells, gender differences in incidence point to a possible role for circulating estrogens in lung tumorigenesis. We sought to determine if use of the anti-estrogen tamoxifen decreases the risk of lung cancer. Methods: We examined incidence rates of second primary lung cancers by categories of tamoxifen treatment among women enrolled in randomized ECOG adjuvant breast cancer trials. Overall, there were 15,875 women in 14 studies from 1978–2002. The duration of tamoxifen treatment varied by study and was alternately categorized as ≤ 1, ≤2 or ≥5 years. Results: We identified 55 second-primary lung cancers over 97,225 person-years of follow-up. 27 second-primary lung cancers occurred among 6,478 women who did not receive tamoxifen versus 28 lung cancers among the 9,397 women who received tamoxifen of any duration. Compared to women without tamoxifen treatment, those treated for fewer than two years had an age-adjusted relative risk for lung cancer of 1.13 (95% CI 0.52–2.32). Similarly, among women treated with tamoxifen for ≥5 years the relative risk for subsequent lung cancer was 0.80 (95% CI 0.40–1.57). Conclusions: We did not observe a strong association between tamoxifen treatment and the risk of second-primary lung cancer in a sample of women who had received tamoxifen as adjuvant therapy for breast cancer. The results are similar to those previously reported (Fisher, JNCI 1998). However, the potential estrogenic activity of tamoxifen may argue for evaluating adjuvant breast cancer trials of aromatase inhibitors for incident second primary lung cancers. No significant financial relationships to disclose.

Arsenic: In Search of an Antidote to a Global Poison

Arsenic. No other element has such a complex and variegated past. As early as 500 B.C. the ancients knew about arsenic, whose name comes from the Greek word for potent. Through the centuries, this “king of poisons” was a common means of homicide. And yet, arsenic’s image has not always been so morbid. People in the Middle Ages wore arsenic amulets around their necks to ward off the bubonic plague, and women in Victorian times applied arsenic compounds to their faces to whiten their complexions. Hippocrates, the father of western medicine, recorded arsenic’s usefulness as a topical remedy for skin ulcers.

CYP1A1 and GSTM1 genetic polymorphisms in lung cancer populations exposed to arsenic in drinking water

Region II of Chile is the most important copper mining area in the world and it shows the highest lung cancer mortality rate in the country (35/100 000). The population in Antofagasta, the main city of Region II, was exposed from 1958 to 1970 to 860 µg m−3 arsenic (As) in drinking water and has currently been declining to 40 µg m−3. Glutathione serves as a reducing agent and glutathione S-transferase (GST) may have an important role in As methylation capacity and body retention. In the current study, the null genotype of GSTM1 and the MspI polymorphism of CYP450 1A1 were investigated in lung cancer patients and in healthy volunteers of Region II. In males, the 2A genotype of MspI represented a highly significant estimated relative lung cancer risk (OR = 2.60). Relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habit (OR = 2.98). In Region II, the cancer mortality rate for As-associated cancers at least partly might be related to differences in As biotransformation. Genetic biomarkers such as 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with a high risk for lung cancer as prevention and protection actions to protect public health.

Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies

Objective To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally occurring radon gasDesign Collaborative analysis of individual data from 13...

The Beta-Carotene and Retinol Efficacy Trial: Incidence of Lung Cancer and Cardiovascular Disease Mortality During 6-Year Follow-up After Stopping -Carotene and Retinol Supplements

The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group. After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided. With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males. The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.

Cancer Incidence Among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study

Chlorpyrifos is one of the most widely used insecticides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 54,383 pesticide applicators were included in this analysis. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed at the time of enrollment (December 1993-December 1997). Poisson regression analysis was used to evaluate the association between chlorpyrifos exposure and cancer incidence after adjustment for potential confounders. All statistical tests were two-sided. A total of 2070 incident malignant neoplasms were diagnosed through 2001. The rate ratio for all cancers combined among chlorpyrifos-exposed applicators compared with nonexposed applicators was 0.97 (95% confidence interval = 0.87 to 1.08). For most cancers analyzed, there was no evidence of an exposure-response relationship. However, the incidence of lung cancer was statistically significantly associated with both chlorpyrifos lifetime exposure-days (P(trend) = .002) and chlorpyrifos intensity-weighted exposure-days (P(trend) = .036). After adjustment for other pesticide exposures and demographic factors, individuals in the highest quartile of chlorpyrifos lifetime exposure-days (>56 days) had a relative risk of lung cancer 2.18 (95% confidence interval = 1.31 to 3.64) times that of those with no chlorpyrifos exposure. Our findings suggest an association between chlorpyrifos use and incidence of lung cancer that deserves further evaluation.