Factors that impact susceptibility to fiber-induced health effects

Our plain-English summary of Factors that impact susceptibility to fiber-induced health effects, by J.E. Below, N.J. Cox, N.K. Fukagawa, et al (Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 2011).

The study

• Authors: J.E. Below, N.J. Cox, N.K. Fukagawa, A. Hirvonen, J.R. Testa
• Journal: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
• Published: 2011;14(1-4):246-66
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos and related fibers are associated with a number of adverse health effects, including malignant mesothelioma (MM), an aggressive cancer that generally develops in the surface serosal cells of the pleural, pericardial, and peritoneal cavities. Although approximately 80% of individuals with MM are exposed to asbestos, fewer than 5% of asbestos workers develop MM. In addition to asbestos, other mineralogical, environmental, genetic, and possibly viral factors might contribute to MM susceptibility. Given this complex etiology of MM, understanding susceptibility to MM needs to be a priority for investigators in order to reduce exposure of those most at risk to known environmental carcinogens. In this review, the current body of literature related to fiber-associated disease susceptibility including age, sex, nutrition, genetics, asbestos, and other mineral exposure is addressed with a focus on MM, and critical areas for further study are recommended.

In plain English

This article was a review, written as a white paper after a December 2009 meeting on asbestos and related mineral fibers sponsored by NIEHS, ATSDR and the U.S. EPA. The authors reviewed published research on factors that may affect susceptibility to disease from fibers, including sex, age, genetics, nutrition, ionizing radiation and other minerals such as erionite. The review focused mainly on malignant mesothelioma (MM). It reported findings from other studies. A U.S. cancer-registry analysis covering 1975 to 2004 found a male-to-female incidence rate ratio of 4.9 for MM. In three villages in Cappadocia, Turkey, where erionite was identified as the cause, 50% or more of all deaths were caused by MM. In one large family tree there, 41 of 87 children with at least one affected parent had MM. Cited studies found the NF2 tumor suppressor gene inactivated in about 40–50% of human MMs. Candidate-gene association studies of inherited risk gave controversial or borderline results. The authors noted that MM studies have suffered from small sample sizes and poorly described exposures, and that little is known about diet and asbestos-related disease. They concluded that the Cappadocian observations support a model in which genetic and environmental factors interact.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published literature (a post-meeting white paper); no new data were collected
• Who was studied: Published studies on susceptibility to fiber-related disease, reviewed for a meeting held December 16–18, 2009, in Research Triangle Park, North Carolina, USA
• Exposure: Asbestos (the amphiboles amosite, crocidolite, tremolite, actinolite and anthophyllite, and the serpentine chrysotile) and other mineral fibers, including erionite and tremolite-contaminated vermiculite from Libby, Montana, plus ionizing radiation. Susceptibility factors reviewed were age, sex, nutrition and genetics.
• Main results:
  • In a U.S. SEER analysis of cases from 1975 to 2004 (Cook et al., 2009), the male-to-female incidence rate ratio for MM was 4.9. MM ranked fourth among the 10 cancers with the largest ratios.
  • In three villages in Cappadocia, Turkey (Karain, Tuzkoy and 'Old' Sarihidir), 50% or more of all deaths were caused by MM, according to studies the review cited. The causative agent was identified as erionite, a zeolite fiber from local volcanic tuff used to build homes.
  • In a 6-generation family tree of 526 people from Tuzkoy (Roushdy-Hammady et al., 2001; Carbone et al., 2002), 41 of 87 children with at least one affected parent had MM. The authors described this as suggestive of autosomal dominant inheritance with reduced penetrance, and noted that the methods and interpretation are debated.
  • Cited studies of MM tumors found the NF2 tumor suppressor gene, located at 22q12, inactivated in about 40–50% of human MMs.
  • More than 30 MM cases from exposure to asbestos-containing vermiculite had been identified from Libby, Montana (Whitehouse et al., 2008). Eleven of these were in people not exposed through their work.
  • A meta-analysis of 21 studies of 1690 MM cases (Lanphear & Buncher, 1992) found that 96% occurred at least 20 years after first exposure, with a mean latency of 32 years.
  • In the cited biomarker study (Robinson et al., 2003), 7 of 40 asbestos-exposed individuals tested positive for elevated SMRP, and 3 of them were diagnosed with MM within 3 years. None of the 33 subjects with normal SMRP levels developed MM within 8 years of follow-up. The review stated that no single marker is specific for MM.
  • Candidate-gene association studies gave conflicting findings for NAT2. Finnish and some other patients showed increased risk with the slow acetylator type, while Italian patients showed increased risk with the fast type. Variants of other genes were implicated only with borderline statistical significance.
  • In a cited diet study of 94 men and women with MM (Muscat & Huncharek, 1996), carrot intake was associated with a significant reduction in MM risk. The association with tomatoes or tomato juice did not reach statistical significance.
  • Two literature reviews of MM in blood relatives (Ascoli et al., 2007; Ugolini et al., 2008) came to differing conclusions. The authors stated that both suggest there is insufficient evidence to implicate a single genetic susceptibility locus.
• The authors' conclusion: The authors concluded that the observations in Cappadocia support a model in which genetic and environmental factors interact in villagers' susceptibility to MM.
• Limitations the authors state:
  • The authors stated that MM studies have suffered from poor statistical power because of small sample sizes, population structure and poorly characterized environmental exposures.
  • The authors stated that practically no data exist on the role of age, gender and disease status in asbestos-related nonmalignant disorders or lung cancer.
  • On ionizing radiation, the authors noted that asbestos exposure is hard to rule out in radiation-exposed people, and that not all reviewed studies reached statistical significance.
  • The authors stated that little is known about nutrients and asbestos-related diseases, and that even less is being investigated.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pericardial, Etiology.

Related studies

• Non-neoplastic and neoplastic pleural endpoints following fiber exposure — V.C. Broaddus, J.I. Everitt, et al. (2011)
• Structured expert judgement approach of the health impact of various chemicals and classes of chemicals — D. Marti, D. Hanrahan, et al. (2024)
• Susceptibility to asbestos-induced and transforming growth factor-beta1-induced fibroproliferative lung disease in two strains of mice — G.S. Warshamana, D.A. Pociask, et al. (2002)
• Health effects of asbestos and nonasbestos fibers — O.Y. Osinubi, M. Gochfeld, et al. (2000)
• Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases — S.X. Huang, M.C. Jaurand, et al. (2011)
• Adverse health effects of fluoro-edenitic fibers: epidemiological evidence and public health priorities — C. Bruno, P. Comba, et al. (2006)

Browse more research in Journal of Toxicology and Environmental Health. Part B, Critical Reviews, or return to medical research.