Case-control Study Of Lung Cancer Research Articles

Spousal smoking as an indicator of total secondhand smoke exposure

This study assessed the utility of spousal smoking as a measure of secondhand smoke exposure. Methods The investigation involved secondary analysis of data from 526 female participants of a lung cancer case-control study from northeastern England. Secondhand smoke exposure was measured in the home (spousal and nonspousal), workplace, and social/other settings over the whole life course. Almost all women (99.1%) had at least 10 years of secondhand smoke exposure from at least one source, most commonly from parental smoking in childhood, and spousal smoking, the workplace, and social settings during adulthood. Spousal smoking was strongly correlated with overall secondhand smoke exposure in the home over the life course but was weakly correlated (Kendall's tau = -.04 to .12) with secondhand smoke exposure from other domestic sources and with secondhand smoke exposure in the workplace or social/other settings. Most women who gave no history of spousal secondhand smoke exposure recalled at least 10 years of secondhand smoke exposure in other settings: in the home through other sources (83.2% > or = 10 "smoker-years"), through workplaces (63.4% > or =10 "exposure-years"), or in social settings (82.0% > or =10 exposure-years). Almost all (96.9%) reported at least 10 years of exposure from at least one of these nonspousal sources. Using spousal smoking as a proxy of total secondhand smoke exposure would have meant that these subjects would have been misclassified as not exposed to secondhand smoke. This misclassification may bias estimates of association with health outcomes toward the null. Studies of the effects of secondhand smoke exposure on health outcomes should evaluate all potential sources of secondhand smoke exposure.

GSTM1 copy number and lung cancer risk

The GSTM1 null genotype is associated with a small increased lung cancer risk when compared to controls with at least one copy of the GSTM1 gene. As two copies of the GSTM1 gene might provide more protection than a single copy, we have determined GSTM1 copy number in a lung cancer case-control study. Cases with incident lung cancer were identified through a Bronchoscopy Unit and two separate hospital based control groups with non-malignant disease were selected with one from the same Bronchoscopy Unit and the other from a chest clinic at the same hospital. Subjects with at least one GSTM1 copy had a decreased lung cancer risk whatever the control group: the odds ratio (95% CI), after adjustment for age, gender and smoking duration, was 0.64 (0.41–0.98) and 0.54 (0.32–0.91) with bronchoscopy and chest clinic controls, respectively. Lung cancer risk varied with GSTM1 copy number with chest clinic controls only: the OR was 0.56 (0.32–0.97) for one copy of the GSTM1 gene and with two copies 0.43 (0.15–1.22), a trend that was significant ( p = 0.02): with bronchoscopy controls the trend was not significant ( p = 0.07). Results then confirm that the presence of GSTM1 provides protection against the risk of lung cancer. In addition there is equivocal evidence that this protection varies with the number of gene copies.

Increased lung cancer risks are similar whether arsenic is ingested or inhaled.

In 1980, the International Agency for Research on Cancer (IARC) determined there was sufficient evidence to support that inorganic arsenic was a human lung carcinogen based on studies involving exposure through inhalation. In 2004, IARC listed arsenic in drinking water as a cause of lung cancer, making arsenic the first substance established to cause human cancer through two unrelated pathways of exposure. It may initially seem counterintuitive that arsenic in drinking water would cause human lung cancer, and even if it did, one might expect risks to be orders of magnitude lower than those from direct inhalation into the lungs. In this paper, we consider lung cancer dose-response relationships for inhalation and ingestion of arsenic by focusing on two key studies, a cohort mortality study in the United States involving Tacoma smelter workers inhaling arsenic, and a lung cancer case-control study involving ingestion of arsenic in drinking water in northern Chile. When exposure was assessed based on the absorbed dose identified by concentrations of arsenic in urine, there was very little difference in the dose-response findings for lung cancer relative risks between inhalation and ingestion. The lung cancer mortality rate ratio estimate was 8.0 (95% CI 3.2-16.5, P<0.001) for an average urine concentration of 1179 microg/l after inhalation, and the odds ratio estimate of the lung cancer incidence rate ratio was 7.1 (95% CI 3.4-14.8, P<0.001) for an estimated average urine concentration of 825 microg/l following ingestion. The slopes of the linear dose-response relationships between excess relative risk (RR-1) for lung cancer and urinary arsenic concentration were similar for the two routes of exposure. We conclude that lung cancer risks probably depend on absorbed dose, and not on whether inorganic arsenic is ingested or inhaled.

Serum Concentrations of Cytokines and Lung Cancer Survival in African Americans and Caucasians

Accumulating evidence suggests a role for inflammation in the development and progression of cancer. Our group recently identified a cytokine gene signature in lung tissue associated with lung cancer prognosis. Therefore, we hypothesized that concentrations of circulating cytokines in serum may be associated with lung cancer survival. Ten serum cytokines, namely, interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, interferon (IFN)-gamma, and tumor necrosis factor-alpha, were assessed in 353 non-small cell lung cancer cases from a case-control study of lung cancer in the greater Baltimore, Maryland area. Cytokines were measured using an ultrasensitive electrochemiluminescence immunoassay. IL-6 serum concentrations (>or=4.0 pg/mL) were associated with significantly poorer survival in both African Americans [hazard ratio (HR), 2.71; 95% confidence interval (CI), 1.26-5.80] and Caucasians (HR, 1.71; 95% CI, 1.22-2.40). IL-10 (HR, 2.62; 95% CI, 1.33-5.15) and IL-12 (HR, 1.98; 95% CI, 1.14-3.44) were associated with lung cancer survival only in African Americans. Some evidence for an association of tumor necrosis factor-alpha levels with survival in Caucasians was observed, although these results were not significant. These hypothesis-generating findings indicate that selected serum cytokine concentrations are associated with lung cancer survival, and indicate that further research is warranted to better understand the mechanistic underpinnings of these associations.

Quantitative Analysis of DNA Methylation Profiles in Lung Cancer Identifies Aberrant DNA Methylation of Specific Genes and Its Association with Gender and Cancer Risk Factors

The global increase in lung cancer burden, together with its poor survival and resistance to classical chemotherapy, underscores the need for identification of critical molecular events involved in lung carcinogenesis. Here, we have applied quantitative profiling of DNA methylation states in a panel of five cancer-associated genes (CDH1, CDKN2A, GSTP1, MTHFR, and RASSF1A) to a large case-control study of lung cancer. Our analyses revealed a high frequency of aberrant hypermethylation of MTHFR, RASSF1A, and CDKN2A in lung tumors as compared with control blood samples, whereas no significant increase in methylation levels of GSTP1 and CDH1 was observed, consistent with the notion that aberrant DNA methylation occurs in a tumor-specific and gene-specific manner. Importantly, we found that tobacco smoking, sex, and alcohol intake had a strong influence on the methylation levels of distinct genes (RASSF1A and MTHFR), whereas folate intake, age, and histologic subtype had no significant influence on methylation states. We observed a strong association between MTHFR hypermethylation in lung cancer and tobacco smoking, whereas methylation levels of CDH1, CDKN2A, GSTP1, and RASSF1A were not associated with smoking, indicating that tobacco smoke targets specific genes for hypermethylation. We also found that methylation levels in RASSF1A, but not the other genes under study, were influenced by sex, with males showing higher levels of methylation. Together, this study identifies aberrant DNA methylation patterns in lung cancer and thus exemplifies the mechanism by which environmental factors may interact with key genes involved in tumor suppression and contribute to lung cancer.

A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk

Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3' untranslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non-small cell lung cancer (NSCLC). let-7 complementary sites (LCS) were sequenced in the KRAS 3' untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (confidence interval, 1.1-4.6; P = 0.02) for NSCLC cancer in patients who smoked <40 pack-years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS overexpression in vitro. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility.

Reliability and accuracy of interview data in non-smoking female lung cancer case-control study

BackgroundValid interview data is critical to the final results of the study. The purpose of this study was to investigate the reliability of epidemiological data obtained in non-smoking female lung cancer case-control study in China.MethodsFifty-six pairs of cases and controls, 10% percent of all the collected subjects were re-interviewed by three interviewers who underwent identical standardized training. A limited number of questions included in the original survey were asked again, the responses from the re-interview were compared with the original interview. Kappa was calculated by negative rates of agreement, positive rates of agreement and total rates of agreement to the accordance degree between the two interviews.ResultsThe Kappa values were all more than 0.5 in all the studied indexes. The Kappa values descended from 0.92 in family history of cancer to 0.56 in oral contraception use. Errors in collecting and classifying data did occur, and were especially common for complicated clinical events, such as a drug exposure occurring many years before.ConclusionWe identified four sources of this variability, three in collecting the data, and one in coding. As a result of these findings, strategies are proposed for improving the quality of interview data obtained in epidemiological research. Before finding a good solution, the strategy of data collecting and coding should be simple and easy to inspect.

Comparison of Statistical Methods for Estimating Genetic Admixture in a Lung Cancer Study of African Americans and Latinos

A variety of methods are available for estimating genetic admixture proportions in populations; however, few investigators have conducted detailed comparisons using empirical data. The authors characterized admixture proportions among self-identified African Americans (n = 535) and Latinos (n = 412) living in the San Francisco Bay Area who participated in a lung cancer case-control study (1998-2003). Individual estimates of genetic ancestry based on 184 informative markers were obtained from a Bayesian approach and 2 maximum likelihood approaches and were compared using descriptive statistics, Pearson correlation coefficients, and Bland-Altman plots. Case-control differences in individual admixture proportions were assessed using 2-sample t tests and logistic regression analysis. Results indicated that Bayesian and frequentist approaches to estimating admixture provide similar estimates and inferences. No difference was observed in admixture proportions between African-American cases and controls, but Latino cases and controls significantly differed according to Amerindian and European genetic ancestry. Differences in admixture proportions between Latino cases and controls were not unexpected, since cases were more likely to have been born in the United States. Genetic admixture proportions provide a quantitative measure of ancestry differences among Latinos that can be used in analyses of genetic risk factors.

Development and Validation of a Lung Cancer Risk Prediction Model for African-Americans

Because existing risk prediction models for lung cancer were developed in white populations, they may not be appropriate for predicting risk among African-Americans. Therefore, a need exists to construct and validate a risk prediction model for lung cancer that is specific to African-Americans. We analyzed data from 491 African-Americans with lung cancer and 497 matched African-American controls to identify specific risks and incorporate them into a multivariable risk model for lung cancer and estimate the 5-year absolute risk of lung cancer. We performed internal and external validations of the risk model using data on additional cases and controls from the same ongoing multiracial/ethnic lung cancer case-control study from which the model-building data were obtained as well as data from two different lung cancer studies in metropolitan Detroit, respectively. We also compared our African-American model with our previously developed risk prediction model for whites. The final risk model included smoking-related variables [smoking status, pack-years smoked, age at smoking cessation (former smokers), and number of years since smoking cessation (former smokers)], self-reported physician diagnoses of chronic obstructive pulmonary disease or hay fever, and exposures to asbestos or wood dusts. Our risk prediction model for African-Americans exhibited good discrimination [75% (95% confidence interval, 0.67-0.82)] for our internal data and moderate discrimination [63% (95% confidence interval, 0.57-0.69)] for the external data group, which is an improvement over the Spitz model for white subjects. Existing lung cancer prediction models may not be appropriate for predicting risk for African-Americans because (a) they were developed using white populations, (b) level of risk is different for risk factors that African-American share with whites, and (c) unique group-specific risk factors exist for African-Americans. This study developed and validated a risk prediction model for lung cancer that is specific to African-Americans and thus more precise in predicting their risks. These findings highlight the importance of conducting further ethnic-specific analyses of disease risk.

Environment And Genetics in Lung cancer Etiology (EAGLE) study: An integrative population-based case-control study of lung cancer

BackgroundLung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease.Methods/DesignWe designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing.DiscussionEAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.

Dietary magnesium and DNA repair capacity as risk factors for lung cancer.

Magnesium (Mg) is required for maintenance of genomic stability; however, data on the relationship between dietary Mg intake and lung cancer are lacking. In an ongoing lung cancer case-control study, we identified 1139 cases and 1210 matched healthy controls with data on both diet and DNA repair capacity (DRC). Dietary intake was assessed using a modified Block-NCI food frequency questionnaire and DRC was measured using the host-cell reactivation assay to assess repair in lymphocyte cultures. After adjustment for potential confounding factors including DRC, the odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer with increasing quartiles of dietary Mg intake were 1.0, 0.83 (0.66-1.05), 0.64 (0.50-0.83) and 0.47 (0.36-0.61), respectively, for all subjects (P-trend < 0.0001). Similar results were observed by histology and clinical stage of lung cancer. Low dietary Mg intake was associated with poorer DRC and increased risk of lung cancer. In joint effects analyses, compared with those with high dietary Mg intake and proficient DRC, the OR (95% CI) for lung cancer in the presence of both low dietary Mg and suboptimal DRC was 2.36 (1.83-3.04). Similar results were observed for men and women. The effects were more pronounced among older subjects (>60 years), current or heavier smokers, drinkers, those with a family history of cancer in first-degree relatives, small cell lung cancer and late-stage disease. These intriguing results need to be confirmed in prospective studies.

Cannabis use and risk of lung cancer: a case–control study

The aim of the present study was to determine the risk of lung cancer associated with cannabis smoking. A case-control study of lung cancer in adults <or=55 yrs of age was conducted in eight district health boards in New Zealand. Cases were identified from the New Zealand Cancer Registry and hospital databases. Controls were randomly selected from the electoral roll, with frequency matching to cases in 5-yr age groups and district health boards. Interviewer-administered questionnaires were used to assess possible risk factors, including cannabis use. The relative risk of lung cancer associated with cannabis smoking was estimated by logistic regression. In total, 79 cases of lung cancer and 324 controls were included in the study. The risk of lung cancer increased 8% (95% confidence interval (CI) 2-15) for each joint-yr of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 5-9) for each pack-yr of cigarette smoking, after adjustment for confounding variables including cannabis smoking. The highest tertile of cannabis use was associated with an increased risk of lung cancer (relative risk 5.7 (95% CI 1.5-21.6)), after adjustment for confounding variables including cigarette smoking. In conclusion, the results of the present study indicate that long-term cannabis use increases the risk of lung cancer in young adults.

A Rapid Outcomes Ascertainment System Improves the Quality of Prognostic and Pharmacogenetic Outcomes from Observational Studies

Case-control and observational studies are popular choices for evaluating molecular prognostic/pharmacogenetic outcomes, but data quality is rarely tested. Using clinical trial and epidemiologic methods, we assessed the quality of prognostic and outcomes data obtainable from a large case-control study of lung cancer. We developed an explicit algorithm (set of standard operating procedures forming a rapid outcomes ascertainment system) that encompassed multiple tests of quality assurance, and quality of data for a range of prognostic and outcomes variables, in several cancers, across several centers and two countries were assessed. Based on these assessments, the algorithm was revised and physicians' clinical practice changed. We reevaluated the quality of outcomes after these revisions. Development of an algorithm with internal quality controls showed specific patterns of data collection errors, which were fixable. Although the major discrepancy rate in retrospective data collection was low (0.6%) when compared with external validated sources, complete data were found in <50% of patients for treatment response rate, toxicity, and documentation of patient palliative symptoms. Prospective data collection and changes to clinical practice led to significantly improved data quality. Complete data on response rate increased from 45% to 76% (P = 0.01, Fisher's exact test), for toxicity data, from 26% to 56% (P = 0.02), and for palliative symptoms, from 25% to 70% (P < 0.05), in one large lung cancer case-control study. Observational studies can be a useful source for studying molecular prognostic and pharmacogenetic outcomes. A rapid outcomes ascertainment system with strict ongoing quality control measures is an excellent means of monitoring key variables.

Correlating observed odds ratios from lung cancer case–control studies to SNP functional scores predicted by bioinformatic tools

Bioinformatic tools are widely utilized to predict functional single nucleotide polymorphisms (SNPs) for genotyping in molecular epidemiological studies. However, the extent to which these approaches are mirrored by epidemiological findings has not been fully explored. In this study, we first surveyed SNPs examined in case–control studies of lung cancer, the most extensively studied cancer type. We then computed SNP functional scores using four popular bioinformatics tools: SIFT, PolyPhen, SNPs3D, and PMut, and determined their predictive potential using the odds ratios (ORs) reported. Spearman's correlation coefficient ( r) for the association with SNP score from SIFT, PolyPhen, SNPs3D, and PMut, and the summary ORs were r = −0.36 ( p = 0.007), r = 0.25 ( p = 0.068), r = −0.20 ( p = 0.205), and r = −0.12 ( p = 0.370), respectively. By creating a combined score using information from all four tools we were able to achieve a correlation coefficient of r = 0.51 ( p < 0.001). These results indicate that scores of predicted functionality could explain a certain fraction of the lung cancer risk detected in genetic association studies and more accurate predictions may be obtained by combining information from a variety of tools. Our findings suggest that bioinformatic tools are useful in predicting SNP functionality and may facilitate future genetic epidemiological studies.

Risk of lung cancer following exposure to carbon black, titanium dioxide and talc: Results from two case–control studies in Montreal

The International Agency for Research on Cancer (IARC) recently evaluated the carcinogenicity of three poorly soluble weakly-toxic substances: carbon black, titanium dioxide and talc. Though there is evidence of carcinogenity in experimental animals for these substances, the evidence in humans is sparse and equivocal. In the context of two large population based case-control studies of lung cancer carried out in Montreal, we were able to study the possible relationships between the exposure to each of these substances and subsequent risk of lung cancer. We were able to distinguish talc used for industrial purposes from that used for cosmetic purposes. Interviews for Study I were conducted in 1979-1986 (857 cases, 533 population controls, 1,349 cancer controls) and interviews for Study II were conducted in 1996-2001 (1,236 cases and 1,512 controls). Detailed lifetime job histories were elicited, and a team of hygienists and chemists evaluated the evidence of exposure to a host of occupational substances. Lung cancer risk was analysed in relation to each exposure, adjusting for several potential confounders, including smoking. Subjects with occupational exposure to carbon black, titanium dioxide, industrial talc and cosmetic talc did not experience any detectable excess risk of lung cancer. The results are consistent with the recent evaluations of the IARC Monographs.

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case-control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3*A/*A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3*A/*A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3*A/*A + GSTP1*B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3*B + GSTP1*A/*A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1*B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1*B genotype, when compared with respective potential protective GST genotypes. This case-control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects.

Cigarette Smoking and Lung Cancer

A recent analysis indicates that the excess odds ratio for lung cancer by smoking is described by a function that is linear in pack-years and exponential in the logarithm of smoking intensity and its square (Cancer Epidemiol Biomarkers Prev. 2006;15:517-523). The model suggests that below 15-20 cigarettes per day there is a "direct exposure rate" effect, ie, the excess odds ratio per pack-year for higher intensity (and shorter duration) smokers is greater than for lower-intensity (and longer duration) smokers. Above 20 cigarettes per day, there is an "inverse-exposure-rate" effect, ie, the excess odds ratio per pack-year for higher intensity smokers is smaller than for lower-intensity smokers. Using pooled data from 2 large case-control studies of lung cancer (the European Smoking and Health Study and the German Radon Study), we evaluated effect modification of the association between smoking and lung cancer. Interaction effects are very specific. Variations in risk of lung cancer with years since cessation of smoking, age, method of inhalation, and type of cigarette result from interactions with smoking intensity, and not total pack-years. In contrast, risk variations by sex result from the interaction with total pack-years, while intensity effects are homogeneous. Risk variations by age at which smoking started result from interactions with both total pack-years and intensity. All intensity interactions are homogeneous across studies. The specificity of the interactions may provide clues for the molecular basis of the smoking and lung cancer relationship.

Age-related differences in factors associated with smoking initiation

We sought to determine whether the influence of two factors known to influence smoking initiation (parental smoking and lower academic attainment) vary by age of smoking initiation and to develop profiles of smokers based on their age of smoking initiation. We analyzed data on demographic and smoking characteristics from 1,447 former and current cancer-free smokers, born between 1912 and 1975, who served as controls in an ongoing lung cancer case-control study, and who reported initiating smoking before their 31st birthday. Parental smoking exerted a significant influence among the youngest initiators (<15 years) only, and the magnitude of the influence from academic attainment decreased with increasing age of initiation. The youngest initiators were less likely to have quit, had smoked for more years, and reported higher levels of nicotine dependence than the oldest initiators. Our results underscore the continued need to target smoking prevention messages toward individuals younger than 15 years. Because the influence of parental smoking was pronounced among the youngest initiators, family smoking dynamics must be addressed to develop effective prevention programs tailored to this at-risk age group.

A Case Control Study of Lung Cancer and Exposure to Chrysotile and Amphibole at a Slovenian Asbestos-Cement Plant

A lung cancer case-control study was conducted in a Slovenian asbestos-cement factory for which unusually good records of asbestos exposures were available. The cohort consisted of all 6714 workers employed at the Salonit Anhovo factory after 31 December 1946 who worked there for at least one day between 1964 and 1994. Fifty-eight histologically confirmed cases of primary lung cancer and 290 controls were selected from the cohort. Working life exposure histories to amphibole and chrysotile forms of asbestos were estimated separately. Airborne asbestos concentrations were low. For example, the arithmetic mean exposure to all forms of asbestos in the highest exposure period (1947-1971) was 1.2 f/cm(3). Chrysotile asbestos made up about 90% of this exposure (mean 1.1 f/cm(3)), whereas amphibole accounted for 10% (0.1 f/cm(3)). Comparing those above and below the 90 percentile of cumulative exposure, the odds ratios for all asbestos, chrysotile and amphibole were 1.5, 1.6 and 2.0, respectively, but confidence intervals were wide. There are only a few asbestos-lung cancer studies with high-quality exposure data and exposures in this low range. Though imprecise, the findings are important to the ongoing debate about asbestos risks.

Aggregation of cancer among relatives of never‐smoking lung cancer patients

The authors evaluated the familial aggregation of lung and other cancers in first-degree relatives of lung cancer patients self-reported to be lifetime never smokers. The data, derived from a large lung cancer case-control study, included 2,465 first-degree relatives of 316 never smoker lung cancer cases and 2,441 first-degree relatives of 318 never smoker controls, frequency matched to the cases on age, gender and ethnicity. The median age of the cases and the controls was 61 years, about 2/3 were women, and about 80% were Caucasian. Overall, there was a 25% excess risk [95% CI (1.05-1.50)] of any type of cancer among the first-degree relatives of cases, and case offspring exhibited a 2-fold excess cancer risk (1.03-4.10) compared with control offspring. There was also a 44% excess risk (1.05-1.97) of young onset cancers (before age 50) among relatives of cases. Smoking case relatives had an increased risk of any cancer [odds ratio (OR) = 1.36 (1.03-1.81)] and a 5.52-fold risk (1.19-25.51) of young onset lung cancer compared with smoking control relatives. Female case relatives had a 58% excess breast cancer risk (1.04-2.43), and case mothers a 2.57-fold breast cancer risk (1.16-4.24). A significant excess of testicular cancer was observed among case male relatives [OR = 12.32 (1.71-88.90)], although based on only 9 cases. The age at lung cancer diagnosis tended to be earlier in case relatives (61.4, SD = 12.9) compared with control relatives (66.2, SD = 11.4; p = 0.07). Our analysis provides further evidence for the importance of genetic factors for lung cancer in never smokers.