Cancer Epidemiology, Biomarkers & Prevention

Our medical research library holds 22 studies published in Cancer Epidemiology, Biomarkers & Prevention (2005–2026). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 22 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: American Association for Cancer Research
• Published: 1991 to the present, United States
• Language: English
• ISSN: 1055-9965 (print), 1538-7755 (electronic)
• Its record in the NLM Catalog

2020s

• Personal Talc Use and Incident Lung Cancer. M.S. Deshmukh, K.G. Lawrence, D.P. Sandler, et al. 2026;35(11):1962-1965. PubMed · Publisher · Free full text

  Abstract

  Background: Talc is a known risk factor for some lung diseases because of its small particle size, commonly aerosolized form, and possible contamination with asbestos, a known lung carcinogen. Personal talc-based body powder use is common among US women, but the association between talc use and lung cancer has not been studied in nonoccupational settings.

  Methods: At enrollment (2003-2009), Sister Study participants reported talc use in the last year and at ages 10 to 13 years. We used Cox proportional hazards models to estimate covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the associations between talc use and incident lung cancer.

  Results: Among 49,592 eligible women, 41% reported using talc in the last year and 641 reported a new lung cancer diagnosis. Self-reported talc use was not consistently associated with incident lung cancer: HR = 0.91 (95% CI, 0.78-1.07) for talc use in the last year; HR = 0.94 (95% CI, 0.80-1.10) for talc use at ages 10 to 13 years.

  Conclusions: No consistent associations were observed between talc use and lung cancer overall, although some suggestive positive associations observed among never-smokers and for lung adenocarcinomas may warrant further investigation.

  Impact: Population-based research on personal care product use is critical to improving our understanding of the impacts of potentially harmful substances, and their known or unknown contaminants, on human health.

  ©2026 American Association for Cancer Research.

• Biomarkers Suitable for Early Detection of Intrathoracic Cancers in Primary Care: A Systematic Review. W. Hamad, B. Grigore, H. Walford, et al. 2025;34(1):19-34. Systematic review PubMed · Publisher · Free full text

  Abstract

  Intrathoracic cancers, including lung cancer, mesothelioma, and thymoma, present diagnostic challenges in primary care. Biomarkers could resolve some challenges. We synthesized evidence on biomarker performance for intrathoracic cancer detection in low-prevalence settings. A search in Embase and MEDLINE included studies that recruited participants with suspected intrathoracic cancer and reported on at least one diagnostic measure for a validated, noninvasive biomarker. Studies were excluded if participants were recruited based on a preestablished diagnosis. A total of 52 studies were included, reporting on 108 individual biomarkers and panels. Carcinoembryonic antigen, CYFRA 21-1, and VEGF were evaluated for lung cancer and mesothelioma. For lung cancer, carcinoembryonic antigen and CYFRA 21-1 were the most studied, with AUCs of 0.48 to -0.90 and 0.48 to -0.83, respectively. Pro-gastrin-releasing peptide (Pro-GRP) and neuron-specific enolase (NSE) had the highest negative predictive values (NPV) (98.2% and 96.9%, respectively), whereas Early Cancer Detection Test - Lung (Early CDT) and miRNA signature classifier panels showed NPVs of 99.3% and 99.0%, respectively, in smokers. For mesothelioma, fibrillin-3 and mesothelin plus osteopontin had AUCs of 0.93 and 0.91, respectively. Thymoma panels (binding AcHR + StrAb and binding AcHR + modulating AcHR + StrAb) had 100% NPVs in patients with myasthenia gravis. The review highlights the performance of some biomarkers. However, few were evaluated in low-prevalence settings. Further evaluation is necessary before implementing these biomarkers for intrathoracic cancers in primary care.

  ©2024 The Authors; Published by the American Association for Cancer Research.

• Mesothelioma Incidence Rates in Australia since 1982: Exploring Age, Period, and Cohort Effects and Future Projections. K. Walker-Bone, M.A. Goodwin, B. Bufton, et al. 2025;34(7):1149-1155. PubMed · Publisher · Free full text

  Abstract

  Background: The use of asbestos-containing products was banned in Australia in 2003. However, the rates of new cases of mesothelioma, which has a very long latent period between exposure and disease, have continued to increase. The aim of this study was to investigate mesothelioma incidence in Australia by year of birth and age-period-cohort analysis and to develop projections of expected mesothelioma cases until 2034.

  Methods: Data were derived from the Australian Cancer Database which provides complete national records of mesothelioma cases notified between 1982 and 2020. Incidence rates were age-standardized to the 2001 Australian standard population to enable comparisons of the population across time. Age-period-cohort models were used to examine the temporal trends of incidence rates by age, calendar year, and birth cohort. Projections for incidence rates of mesothelioma for 2020 to 2034 were estimated using Nordpred models.

  Results: Graphs of age-standardized incidence rates of mesothelioma suggest a birth cohort effect, and the age-period-cohort model confirmed this. There was a birth cohort effect in all cohorts born before 1960, strongest in cohorts born during 1920 to 1949. Projection modeling to 2034 suggested that the age-standardized rates will continue to decline whereas crude incidence rates of mesothelioma will stabilize and then gradually decline, mostly among people of 60 to 84 years of age.

  Conclusions: The findings are consistent with the greatest risk of mesothelioma in Australia occurring in cohorts with the highest levels of historical cumulative occupational exposure, showing the value of a ban on asbestos.

  Impact: The number of new cases of mesothelioma per year is not expected to decline until after 2030.

  ©2025 The Authors; Published by the American Association for Cancer Research.

• Airflow Limitation Increases Lung Cancer Risk in Smokers: The Lifelines Cohort Study. Y. Du, G. Sidorenkov, H.J.M. Groen, et al. 2022;31(7):1442-1449. PubMed · Publisher · Free full text

  Abstract

  Background: The relationship between smoking, airflow limitation, and lung cancer occurrence is unclear. This study aims to evaluate the relationship between airflow limitation and lung cancer, and the effect modification by smoking status.

  Methods: We included participants with spirometry data from Lifelines, a population-based cohort study from the Northern Netherlands. Airflow limitation was defined as FEV1/FVC ratio < 0.7. The presence of pathology-confirmed primary lung cancer during a median follow-up of 9.5 years was collected. The Cox regression model was used and hazard ratios (HR) with 95% confidence interval (95% CI) were reported. Adjusted confounders included age, sex, educational level, smoking, passive smoking, asthma status and asbestos exposure. The effect modification by smoking status was investigated by estimating the relative excess risk due to interaction (RERI) and the ratio of HRs with 95% CI.

  Results: Out of 98,630 participants, 14,200 (14.4%) had airflow limitation. In participants with and without airflow limitation, lung cancer incidence was 0.8% and 0.2%, respectively. The adjusted HR between airflow limitation and lung cancer risk was 1.7 (1.4-2.3). The association between airflow limitation and lung cancer differed by smoking status [former smokers: 2.1 (1.4-3.2), current smokers: 2.2 (1.5-3.2)] and never smokers [0.9 (0.4-2.1)]. The RERI and ratio of HRs was 2.1 (0.7-3.4) and 2.5 (1.0-6.5) for former smokers, and 4.6 (95% CI, 1.8-7.4) and 2.5 (95% CI, 1.0-6.3) for current smokers, respectively.

  Conclusions: Airflow limitation increases lung cancer risk and this association is modified by smoking status.

  Impact: Ever smokers with airflow limitation are an important target group for the prevention of lung cancer.

  ©2022 The Authors; Published by the American Association for Cancer Research.

• Multiple Primary Cancers in Patients Undergoing Tumor-Normal Sequencing Define Novel Associations. Y.L. Liu, K.A. Cadoo, S. Mukherjee, et al. 2022;31(2):362-371. Comment PubMed · Publisher · Free full text

  Abstract

  Background: Cancer survivors are developing more subsequent tumors. We sought to characterize patients with multiple (≥2) primary cancers (MPC) to assess associations and genetic mechanisms.

  Methods: Patients were prospectively consented (01/2013-02/2019) to tumor-normal sequencing via a custom targeted panel (MSK-IMPACT). A subset consented to return of results of ≥76 cancer predisposition genes. International Agency for Research on Cancer (IARC) 2004 rules for defining MPC were applied. Tumor pairs were created to assess relationships between cancers. Age-adjusted, sex-specific, standardized incidence ratios (SIR) for first to second cancer event combinations were calculated using SEER rates, adjusting for confounders and time of ascertainment. Associations were made with germline and somatic variants.

  Results: Of 24,241 patients, 4,340 had MPC (18%); 20% were synchronous. Most (80%) had two primaries; however, 4% had ≥4 cancers. SIR analysis found lymphoma-lung, lymphoma-uterine, breast-brain, and melanoma-lung pairs in women and prostate-mesothelioma, prostate-sarcoma, melanoma-stomach, and prostate-brain pairs in men in excess of expected after accounting for synchronous tumors, known inherited cancer syndromes, and environmental exposures. Of 1,580 (36%) patients who received germline results, 324 (21%) had 361 pathogenic/likely pathogenic variants (PV), 159 (44%) in high penetrance genes. Of tumor samples analyzed, 55% exhibited loss of heterozygosity at the germline variant. In those with negative germline findings, melanoma, prostate, and breast cancers were common.

  Conclusions: We identified tumor pairs without known predisposing mutations that merit confirmation and will require novel strategies to elucidate genetic mechanisms of shared susceptibilities.

  Impact: If verified, patients with MPC with novel phenotypes may benefit from targeted cancer surveillance.

  ©2021 American Association for Cancer Research.

• Comparing Age at Cancer Diagnosis between Hispanics and Non-Hispanic Whites in the United States. H. Parada, A.H. Vu, P.S. Pinheiro, et al. 2021;30(10):1904-1912. PubMed · Publisher · Free full text

  Abstract

  Background: Population age structure may confound the comparison of age at cancer diagnosis across racial/ethnic groups. We compared age at cancer diagnosis for U.S. Hispanics, a population that is younger on average, and non-Hispanic whites (NHW), before and after adjustment for the age structure of the source population.

  Methods: We used Surveillance, Epidemiology, and End Results data from 18 U.S. regions in 2015 for 34 cancer sites to calculate crude and adjusted (using age- and sex-specific weights) mean ages at diagnosis. Differences in age at diagnosis comparing Hispanics to NHWs (δ) were assessed using independent sample t tests.

  Results: Crude mean ages at diagnosis were lower among Hispanic males and females for all sites combined and for most cancer sites. After age-adjustment, Hispanic (vs. NHW) males remained younger on average at diagnosis of chronic myeloid leukemia [δ = -6.1; 95% confidence interval (CI), -8.1 to -4.1 years], testicular cancer (δ =-4.7; 95% CI, -5.4 to -4.0), Kaposi sarcoma (δ =-3.6; 95% CI,-6.3 to -0.8), mesothelioma (δ =-3.0; 95% CI,-4.3 to -1.7), and anal cancer (δ =-2.4; 95% CI, -3.9 to -0.8), and older at diagnosis of gallbladder cancer (δ = +3.8; 95% CI, 1.8 to 5.7) and Hodgkin's lymphoma (δ = +7.5; 95% CI, 5.7 to 9.4), and Hispanic (vs. NHW) females remained younger at diagnosis of mesothelioma (δ = -3.7; 95% CI, -6.7 to -0.7) and gallbladder cancer (δ = -3.0; 95% CI, -4.3 to -1.7) and older at diagnosis of skin cancer (δ = +3.8; 95% CI, 3.1 to 4.5), cervical cancer (δ = +4.1; 95% CI, 3.3 to 4.8), and Hodgkin's lymphoma (δ = +7.0; 95% CI, 5.0 to 9.1).

  Conclusions: On average, Hispanics are diagnosed with cancer at younger ages than NHWs; however, for many cancers these differences reflect the younger age structure in Hispanics.

  Impact: Population age structure should be considered when comparing age at cancer diagnosis across racial/ethnic groups.

  ©2021 American Association for Cancer Research.

• Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network. H.I. Pass, M. Alimi, M. Carbone, et al. 2020;29(12):2524-2540. Review PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm, which can be treated successfully only if correctly diagnosed and treated in early stages. The asbestos-exposed population serves as a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. This review details the recent work with biomarker development in MPM and the contributions of the NCI Early Detection Research Network Biomarker Developmental Laboratory of NYU Langone Medical Center. The literature of the last 20 years was reviewed to comment on the most promising of the blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms as well as novel studies such as "breath testing" are covered. Soluble mesothelin-related proteins (SMRP) have been characterized extensively and constitute an FDA-approved biomarker in plasma with diagnostic, monitoring, and prognostic value in MPM. Osteopontin is found to be a valuable prognostic biomarker for MPM, while its utility in diagnosis is slightly lower. Other biomarkers, such as calretinin, fibulin 3, and High-Mobility Group Box 1 (HMGB1), remain under study and need international validation trials with large cohorts of cases and controls to demonstrate any utility. The EDRN has played a key role in the development and testing of MPM biomarkers by enlisting collaborations all over the world. A comprehensive understanding of previously investigated biomarkers and their utility in screening and early diagnosis of MPM will provide guidance for further future research.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."

  ©2020 American Association for Cancer Research.

• Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma. F. Cerciello, M. Choi, S.L. Sinicropi-Yao, et al. 2020;29(10):1973-1982. PubMed · Publisher · Free full text

  Abstract

  Background: We have verified a mass spectrometry (MS)-based targeted proteomics signature for the detection of malignant pleural mesothelioma (MPM) from the blood.

  Methods: A seven-peptide biomarker MPM signature by targeted proteomics in serum was identified in a previous independent study. Here, we have verified the predictive accuracy of a reduced version of that signature, now composed of six-peptide biomarkers. We have applied liquid chromatography-selected reaction monitoring (LC-SRM), also known as multiple-reaction monitoring (MRM), for the investigation of 402 serum samples from 213 patients with MPM and 189 cancer-free asbestos-exposed donors from the United States, Australia, and Europe.

  Results: Each of the biomarkers composing the signature was independently informative, with no apparent functional or physical relation to each other. The multiplexing possibility offered by MS proteomics allowed their integration into a single signature with a higher discriminating capacity than that of the single biomarkers alone. The strategy allowed in this way to increase their potential utility for clinical decisions. The signature discriminated patients with MPM and asbestos-exposed donors with AUC of 0.738. For early-stage MPM, AUC was 0.765. This signature was also prognostic, and Kaplan-Meier analysis showed a significant difference between high- and low-risk groups with an HR of 1.659 (95% CI, 1.075-2.562; P = 0.021).

  Conclusions: Targeted proteomics allowed the development of a multianalyte signature with diagnostic and prognostic potential for MPM from the blood.

  Impact: The proteomic signature represents an additional diagnostic approach for informing clinical decisions for patients at risk for MPM.

  ©2020 American Association for Cancer Research.

2010s

• Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies. L. Santarelli, S. Gaetani, F. Monaco, et al. 2019;28(1):119-126. PubMed · Publisher

  Abstract

  Background: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies.

  Methods: Four groups of patients were included in the study, including patients with asbestos-related (NSCLCAsb) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population.

  Results: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion.

  Conclusions: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis.

  Impact: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.

  ©2018 American Association for Cancer Research.

• Baseline serum β-carotene concentration and mortality among long-term asbestos-exposed insulators. D. Hashim, D. Gaughan, P. Boffetta, et al. 2015;24(3):555-60. PubMed · Publisher

  Abstract

  Background: Although interventional trials demonstrated that moderate-dose β-carotene supplementation increases lung cancer mortality in smokers and asbestos-exposed workers, differences in serum concentrations in absence of supplementation have not been studied in asbestos-exposed workers.

  Methods: A mortality analysis was performed to assess the relationship of nonsupplemented serum β-carotene to all-cause and cancer mortalities using 1981 to 1983 serum β-carotene concentration measurements from 2,646 U.S. white male insulators (mean age, 57.7 years). Multivariable-adjusted Cox proportional hazard models that included terms for age, duration of asbestos exposure, smoking, season, and region were fitted to estimate mortality HRs and 95% confidence intervals (CI) according to serum β-carotene concentrations.

  Results: Median follow-up was 12.8 years and 984 (33.8%) subjects died during the follow-up period, including 415 deaths from overall cancer and 219 deaths from lung cancer. The overall mortality HR for a serum β-carotene increase of 10 μg/dL was 0.97 (95% CI, 0.96-0.99). Compared with the lowest quartile, HRs were 0.90 (95% CI, 0.76-1.07) for the second (38-65 μg/dL), 0.80 (95% CI, 0.67-0.96) for the third (66-104 μg/dL), and 0.63 (95% CI, 0.51-0.77) for the highest serum β-carotene quartile (≥105 μg/dL). There was no association between serum β-carotene and overall cancer mortality (HR, 1.00; 95% CI, 0.97-1.02) or lung cancer mortality (HR, 0.99; 95% CI, 0.96-1.02).

  Conclusions: Higher nonsupplemented serum β-carotene concentrations were negatively associated with all-cause mortality among asbestos-exposed individuals.

  Impact: Serum β-carotene can be a marker of one or more determinants of reduced mortality in asbestos-exposed workers. Cancer Epidemiol Biomarkers Prev; 24(3); 555-60. ©2014 AACR.

  ©2014 American Association for Cancer Research.

• Genome-wide Gene-Asbestos Exposure Interaction Association Study Identifies a Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk. C.Y. Liu, I. Stücker, C. Chen, et al. 2015;24(10):1564-73. PubMed · Publisher · Free full text

  Abstract

  Background: Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies.

  Methods: We conducted an asbestos exposure-gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNP) with gene-asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP-asbestos exposure interaction effects on lung cancer risk.

  Results: We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 × 10(-7) by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status, and center-adjusted ORs of 1.34 [95% confidence interval (CI), 1.18-1.51], 1.24 (95% CI, 1.14-1.35), 1.28 (95% CI, 1.17-1.40), and 1.26 (95% CI, 1.15-1.38), respectively, for lung cancer risk.

  Conclusion: Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure-related lung cancer.

  Impact: To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk.

  ©2015 American Association for Cancer Research.

• Strengths, weaknesses, and opportunities of diagnostic breathomics in pleural mesothelioma-a hypothesis. K. Lamote, K. Nackaerts, J.P. van Meerbeeck. 2014;23(6):898-908. PubMed · Publisher

  Abstract

  Past and present asbestos use will reflect in increasing numbers of mesothelioma cases in the next decades, diagnosed at a late stage and with a dismal prognosis. This stresses the need for early detection tools, which could improve patients' survival. Recently, breath analysis as a noninvasive and fast diagnostic tool has found its way into biomedical research. High-throughput breathomics uses spectrometric, chromatographic, and sensor techniques to diagnose asbestos-related pulmonary diseases based upon volatile organic compounds (VOC) in breath. This article reviews the state-of-the-art available breath analyzing techniques and provides the insight in the current use of VOCs as early diagnostic or prognostic biomarkers of mesothelioma to stimulate further research in this field. Cancer Epidemiol Biomarkers Prev; 23(6); 898-908. ©2014 AACR.

  ©2014 American Association for Cancer Research.

• Does exposure to asbestos cause ovarian cancer? A systematic literature review and meta-analysis. A. Reid, N. de Klerk, A.W. Musk. 2011;20(7):1287-95. Meta-analysis · Systematic review PubMed · Publisher

  Abstract

  Introduction: The asbestos and ovarian cancer relationship is not well understood because of small numbers of women exposed to asbestos, small numbers of cases, and misclassification of peritoneal mesothelioma as ovarian cancer on death certificates. The aim of this study was to conduct a meta-analysis to quantify the evidence that exposure to asbestos causes ovarian cancer.

  Methods: Fourteen cohort and two case-control studies were identified in Medline searches from 1950 to 2008.

  Results: Statistically significant excess mortality was reported in four of the cohort studies, all of which determined their outcomes from the death certificate. Peritoneal mesotheliomas were reported in these studies, two of which reexamined pathology specimens and reported disease misclassification. Exposure-response relationships were inconsistent. When all studies were included in a meta-analysis, the effect size was 1.75 (95% CI, 1.45-2.10) attenuating to 1.29 (95% CI, 0.97-1.73) in studies with confirmed ovarian cancers.

  Conclusion: Taken without further analysis, women thought to have ovarian cancer had an increased rate in the meta-analysis if reporting having been exposed to asbestos, compared with reference populations. This result may have occurred because of disease misclassification.

  ©2011 AACR

• Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma. J. Creaney, N.J. Olsen, F. Brims, et al. 2010;19(9):2238-46. PubMed · Publisher

  Abstract

  Background: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma.

  Methods: Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestos-exposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay.

  Results: Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis.

  Conclusion: In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group.

  Impact: Future studies examining a combination of biomarkers could improve sensitivity of screening.

  (c)2010 AACR.

2000s

• Asbestos exposure and gestational trophoblastic disease: a hypothesis. A. Reid, J. Heyworth, N. de Klerk, et al. 2009;18(11):2895-8. Case report PubMed · Publisher

  Abstract

  Among 2,968 women and girls exposed to crocidolite (blue asbestos) at Wittenoom, three cases of choriocarcinoma and three cases of hydatidiform mole have been identified (crude incidence rate of 9.9 per 1000 women and 1.7 per 1000 deliveries for choriocarcinoma and hydatidiform mole, respectively). The women with choriocarcinoma were resident at Wittenoom at the time of disease development, whereas hydatidiform mole occurred much later in women who had first been exposed to asbestos as young girls. Four of the six cases were known to have lived with asbestos company workers who brought their dusty work-clothes home for washing. Asbestos fibers have been reported in the lung, the pleural and peritoneal mesothelium, and the human ovary. They have also been detected in placental digests of live and stillborn infants. This cluster of gestational trophoblastic diseases has some biological plausibility for asbestos causation. Taking an occupational and residential history and examining pathologic specimens for asbestos fibers or bodies may prove useful in patients with gestational trophoblastic disease.

• Gynecologic and breast cancers in women after exposure to blue asbestos at Wittenoom. A. Reid, A. Segal, J.S. Heyworth, et al. 2009;18(1):140-7. PubMed · Publisher

  Abstract

  Introduction: Animal studies have suggested an association between asbestos and ovarian cancer, and asbestos fibers have been detected in human ovaries. Sexual intercourse may introduce asbestos fibers into the vagina and to the cervix and ovaries. Occupational cohorts have reported excess mortality from reproductive cancers, but exposure-response relationships are inconsistent. We examine the incidence and exposure-response relationships of these cancers among 2,968 women and girls exposed to blue asbestos at Wittenoom, Western Australia.

  Methods: 2,552 women were residents of the town and 416 worked for the asbestos company (Australian Blue Asbestos). Standardized incidence ratios compared the Wittenoom women with the Western Australian population. A nested case-control design and conditional logistic regression examined exposure-response relationships.

  Results: Ovarian (standardized incidence ratio, 1.27), cervical (standardized incidence ratio, 1.44), and uterine cancer (standardized incidence ratio, 1.23) increased but not statistically significantly among the Wittenoom women compared with the Western Australian population. Among the Australian Blue Asbestos workers, cervical cancer was twice that of the Western Australian population (standardized incidence ratio, 2.38), but ovarian cancer was less (standardized incidence ratio, 0.65). Women who first arrived at Wittenoom aged >or=40 years had an odds ratio of 13.9 (95% confidence interval, 2.2-90.2) for cervical cancer compared with those aged <15 years at first arrival. Women who lived with or washed the clothes of an Australian Blue Asbestos worker did not have an increased risk for any of the gynecologic or breast cancers.

  Discussion: There is no consistent evidence of an increased risk for gynecologic and breast cancers among the women from Wittenoom. Ovarian cancers and peritoneal mesotheliomas were not misclassified in this cohort.

• Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure. J.A. Rodríguez Portal, E. Rodríguez Becerra, D. Rodríguez Rodríguez, et al. 2009;18(2):646-50. PubMed · Publisher

  Abstract

  Background: Malignant pleural mesothelioma (MPM) results from malignant transformation of mesothelial cells. Past asbestos exposure represents a major risk factor for MPM and other benign pleural disease. Soluble mesothelin-related peptides (SMRP) have been regarded as a promising serum biomarker for MPM. The aim of this study was to investigate serum levels of SMRP in malignant and nonmalignant asbestos-related pleural disease.

  Patients: Four groups of patients were investigated: group 1 composed of 48 healthy subjects, group 2 composed of 177 patients with previous asbestos exposure and no pleural disease, group 3 composed of 36 patients with MPM, and group 4 composed of 101 patients with previous asbestos exposure and benign pleural disease. Serum SMRP levels were determined by ELISA.

  Results: Serum SMRP levels were significantly higher among group 3 than the other three groups. There were no differences in SMRP concentrations between groups 2 and 4. Subjects exposed to asbestos had higher SMRP concentrations than normal control subjects regardless of the presence of pleural disease. The area under the receiver operating characteristic curve for SMRP values was 0.75 (95% confidence interval, 0.68-0.83). The SMRP level at 0.55 nmol/L/L was determined as the most optimal cutoff value with resulting sensitivity and specificity of 72% and 72% for the diagnosis of MPM.

  Conclusions: These data attest to good diagnostic sensitivity and specificity of SMRP for the diagnosis of malignant mesothelioma. We have also shown that serum SMRP levels might serve as a marker of asbestos exposure.

• Sex disparities in cancer incidence by period and age. M.B. Cook, S.M. Dawsey, N.D. Freedman, et al. 2009;18(4):1174-82. PubMed · Publisher · Free full text

  Abstract

  Background: Cancer epidemiology articles often point out that cancer rates tend to be higher among males than females yet rarely is this theme the subject of investigation.

  Methods: We used the Surveillance, Epidemiology and End Results program data to compute age-adjusted (2000 U.S. standard population) sex-specific incidence rates and male-to-female incidence rate ratios (IRR) for specific cancer sites and histologies for the period 1975 to 2004.

  Results: The 10 cancers with the largest male-to-female IRR were Kaposi sarcoma (28.73), lip (7.16), larynx (5.17), mesothelioma (4.88), hypopharynx (4.13), urinary bladder (3.92), esophagus (3.49), tonsil (3.07), oropharynx (3.06), and other urinary organs (2.92). Only 5 cancers had a higher incidence in females compared with males: breast (0.01), peritoneum, omentum, and mesentery (0.18), thyroid (0.39), gallbladder (0.57), and anus, anal canal, and anorectum (0.81). Between 1975 and 2004, the largest consistent increases in male-to-female IRR were for cancers of the tonsil, oropharynx, skin excluding basal and squamous, and esophagus, whereas the largest consistent decreases in IRR were for cancers of the lip and lung and bronchus. Male-to-female IRRs varied considerably by age, the largest increases of which were for ages 40 to 59 years for tonsil cancer and hepatocellular carcinoma. The largest decreases in male-to-female IRR by age, meanwhile, were for ages 30 to 49 years for thyroid cancer, ages >70 years for esophageal squamous cell carcinoma, and ages >30 years for lung and bronchus cancer.

  Conclusion: These observations emphasize the importance of sex in cancer etiopathogenesis and may suggest novel avenues of investigation.

• Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study. M. Amati, M. Tomasetti, M. Scartozzi, et al. 2008;17(1):163-70. PubMed · Publisher

  Abstract

  Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2'-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor beta, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor beta (VEGFbeta)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor beta, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFbeta can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFbeta, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

• The CREST biorepository: a tool for molecular epidemiology and translational studies on malignant mesothelioma, lung cancer, and other respiratory tract diseases. D. Ugolini, M. Neri, P.A. Canessa, et al. 2008;17(11):3013-9. PubMed · Publisher

  Abstract

  Objectives: The Cancer of RESpiratory Tract (CREST) biorepository was established to investigate biological mechanisms and to develop tools and strategies for primary and secondary prevention of respiratory tract cancer. The CREST biorepository is focused on pleural malignant mesothelioma, a rare and severe cancer linked to asbestos exposure whose incidence is particularly high in the Ligurian region.

  Methods: The CREST biorepository includes biological specimens from (a) patients with pleural malignant mesothelioma and lung cancer, (b) patients with nonneoplastic respiratory conditions, and (c) control subjects. Whole blood, plasma, serum, lymphocytes, pleural fluid, saliva, and biopsies are collected, and a questionnaire is administered. Collection, transportation, and storage are done according to international standards.

  Results: As of January 31, 2008, the overall number of subjects recruited was 1,590 (446 lung cancer, 209 pleural malignant mesothelioma, and 935 controls). The biorepository includes a total of 10,055 aliquots (4,741 serum; 3,082 plasma; 1,599 whole blood; 633 pleural fluid; and 561 lymphocytes) and 107 biopsies. Demographic, clinical, and epidemiologic information is collected for each subject and processed in a dedicated database.

  Conclusions: The CREST biorepository is a valuable tool for molecular epidemiology and translational studies. This structure relies on a network of contacts with local health districts that allows for an active search for patients. This is a particularly efficient approach, especially when the object of the study is a rare cancer type. The CREST experience suggests that the presence of limited resources can be overcome by the biorepository specialization, the high quality of the epidemiologic information, and the variety of samples.

• Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers. J.Y. Choi, M.L. Neuhouser, M. Barnett, et al. 2007;16(6):1115-20. Randomized trial PubMed · Publisher

  Abstract

  Oxidative stress, associated with aging and inflammation, is likely to play a role in the etiology of prostate cancer. We evaluated potential associations between gene variants that result in reduced neutralization of reactive oxygen species (ROS; MnSOD Ala-16Val, CAT -262 C>T, and GPX1 Pro200Leu) and prostate cancer risk among 724 men with incident prostate cancer who participated in the Carotene and Retinol Efficacy Trial (CARET) cohort, a randomized trial for the prevention of lung cancer among men with a history of smoking and/or asbestos exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Nested case-control analyses included study participants with available DNA (n = 533 cases and 1,470 controls), matched for race, age, and length of follow-time. Overall, there were no associations between genotypes of MnSOD, CAT, and GPX1 and prostate cancer risk, although among men diagnosed before age 65, CAT TT genotype was associated with increased risk (OR, 2.0; 95% CI, 0.97-3.95). Further analyses stratified by factors related to environmental oxidative stress exposures did not modify associations. When calculating the number of risk alleles of MnSOD, CAT, and GPX1 hypothetically related to reduced protection against ROS, there was a nonsignificant relationship between prostate cancer and carriage of five or more risk alleles, in comparison to men with less than five risk alleles (OR, 2.0; 95% CI, 0.90-4.42). In conclusion, it does not seem that variants in MnSOD, CAT, or GPX1 have an influence on prostate cancer risk in this cohort of men who were smokers or exposed to asbestos, although it is possible that cumulative defects in protection from oxidative stress may result in increased risk of the disease.

• A molecular epidemiology case control study on pleural malignant mesothelioma. C. Bolognesi, F. Martini, M. Tognon, et al. 2005;14(7):1741-6. PubMed · Publisher

  Abstract

  Pleural malignant mesothelioma is an uncommon neoplasm usually associated with asbestos exposure. The increasing incidence of malignant mesothelioma cases involving individuals with low levels of asbestos exposure suggests a complex carcinogenetic process with the involvement of other cofactors. Cytogenetic studies revealed the complexity of the genetic changes involved in this neoplasm reflecting the accumulation of genomic damage. One of the most used methodologies for assessing genomic damage is the cytokinesis-blocked micronucleus test applied in peripheral blood lymphocytes (PBL). This approach allows the detection of chromosomal alterations expressed in binucleated cells after nuclear division in vitro. This marker could provide a tool for assessing genetically determined constitutional differences in chromosomal instability. A biomonitoring study was carried out to evaluate the micronuclei frequency in PBLs of patients with pleural malignant mesothelioma with respect to lung cancer, healthy, and risk controls as a marker of cancer susceptibility in correlation with the presence of SV40. A significant increased micronuclei frequency was observed in patients with malignant mesothelioma in comparison with all the other groups, the mean micronuclei frequency was double in patients with malignant mesothelioma compared with healthy controls, risk controls, and patients with lung adenocarcinoma (median 11.4 binucleated cells with micronuclei/1,000 binucleated cells versus 6.2, 6.1, and 5.1, respectively). Our data indicate that human T lymphocyte samples carry DNA sequences coding for SV40 large T antigen at low prevalence, both in cancer cases and controls. Evidence of cytogenetic damage revealed as micronuclei frequency in mesothelioma cancer patients could be related to exogenous and endogenous cofactors besides asbestos exposure.

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