The double-edged sword of meat preservation: a review of nitrosamine genotoxicity, exposure in the egyptian market, and future alternatives

Diet, nutrition and cancer: public, media and scientific confusion

Introduction to 2021 WHO Classification of Thoracic Tumors

Lessons learned from research on air pollution and other particles in the toxicology of nanomaterials and vice versa.

The coal epidemic

Public health and evidence-informed policy-making: The case of a commonly used herbicide.

Every year, millions of people climb in various states of undress into warm, glowing tanning beds, where during a typical 2- to 15-minute session they’ll absorb a controlled dose of ultraviolet (UV) radiation at an intensity up to two to three times stronger than the sunlight striking the equator at noon. The tanning industry has grown rapidly since the 1980s,1 rising to an estimated 28 million users in the United States.2 This rise has been accompanied by an increase in diagnoses of skin cancer. The reasons behind the rising skin cancer diagnoses remain open to debate. Some experts attribute the rise to more frequent skin cancer screening, whereas others blame environmental and behavioral risk factors, particularly changes in UV exposure. In this latter context, UV-emitting tanning beds—classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC)3—have come under growing scrutiny. People tan to look healthy, but looks can be deceiving; UV radiation causes all three types of skin cancer. Melanoma, a tumor of the cells that produce the skin pigment melanin, is the rarest but deadliest type, accounting for 75% of skin cancer deaths worldwide.4 According to the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program, melanoma incidence among U.S. whites (who develop the disease more often than other races) rose from 8.7 cases per 100,000 people in 1975 to 28 cases per 100,000 in 2009.5 Most of that increase occurred in older men, who rarely tan indoors. But a closer look at the age-stratified SEER data reveals that melanoma rates among white girls and women aged 15–39 rose by 3.6% per year between 1992 and 2006, compared with a 2% increase per year among boys and men of the same ages.6 Although they’re not tracked by SEER, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC)—the other two types of skin cancer—also appear to be on the rise, according to regional studies from the United States and Europe. A recent study by Anne Marie Skellett, a consulting dermatologist at Norfolk and Norwich University Hospital, reveals that BCC diagnoses among people under age 30 in the United Kingdom jumped 145% between 1981 and 2006.7 Statistics such as these have prompted 33 U.S. states and some municipalities to ban or restrict indoor tanning among children under age 18.8 California’s ban, signed into law in October 2011, was the first,9 followed by Vermont in April 201210 and the city of Chicago the following June.11 Other states have introduced legislation to limit indoor tanning among minors.8 Melanoma in the United States Scanning electron micrograph of a melanoma cell magnified 8,000 times Mary Brady, an associate professor of surgery at Weill Medical College in New York and the author of an editorial on indoor tanning that appeared in the May 2012 issue of the Journal of Clinical Oncology,12 says the bans make sense. “We legislate against smoking in kids less than 18, and that sends a strong message that there’s something wrong with it,” she says. “We need to send the same message on indoor tanning.” But the bans have drawn a backlash from the tanning bed industry, whose representatives say they’ve been unfairly and incorrectly singled out. John Overstreet, executive director at the Indoor Tanning Association in Washington, DC, describes the evidence linking indoor tanning to skin cancer as speculation and advocacy science reported by the media as fact. He points out that UV light triggers skin cells to produce vitamin D, which may have cancer-protective effects. “It’s frustrating,” he says. “There’s no doubt that repeated overexposure to UV or burning can cause skin problems, but you also have to look at the health benefits, and that issue always gets lost.”

Between 1972 and 1996, the International Agency for Research on Cancer (IARC) identified 282 chemicals as having experimental evidence "sufficient" to conclude that the chemicals cause cancer in animals. Of the 282 IARC animal carcinogens, 7% (20) also had "sufficient" evidence from epidemiology studies. "Limited" human evidence was available for 5% (13) of the 282 IARC animal carcinogens. A 1996 IARC international compendium of cancer studies indicated that epidemiologic studies of chemicals determined by IARC to cause cancer in both humans and animals were considerably more common than studies of chemicals determined to cause cancer in animals but for which human data were inadequate or limited. Of the 1,101 studies reported to IARC by investigators, the IARC animal carcinogens, with the most ongoing studies were asbestos (50 studies) and benzene (26 studies). Both chemicals have sufficient evidence of carcinogenicity from studies of humans. There were epidemiologic studies ongoing for 65% (13/20) of the chemicals for which evidence of carcinogenicity was sufficient in both animals and humans. Epidemiologic studies were reported to IARC for 12% (30/247) of the IARC animal carcinogens for which human data were inadequate or for which no human data were available. Two factors appear critical in determining whether an IARC animal carcinogen becomes the subject of an epidemiologic study: the likelihood of overcoming methodological obstacles to carrying out successful epidemiologic studies, and the economic and/or regulatory interest in the chemical.

The International Agency for Research on Cancer (IARC) Monographs Programme plays an important role in cancer prevention by identifying potential carcinogenic hazards. However, the terminology used in IARC’s classifications and Monographs can confuse the public, health professionals, and policymakers. Terms like “carcinogenic to humans” imply causation, although classifications only indicate increased risk under certain conditions. For example, the lifetime incidence of mesothelioma among firefighters is approximately 14 in 10,000, compared to 7 in 10,000 in the general population. Despite doubling the risk, occupational exposure as a firefighter does not cause this type of cancer in 9,986 out of 10,000 firefighters. However, the IARC concludes that “occupational exposure as a firefighter causes mesothelioma” (IARC Working Group on the Identification of Carcinogenic Hazards to Humans. Occupational Exposure as a Firefighter. Lyon: IARC; 2023. pp. 1–730. PMID: 37963216). In addition, the lack of essential information about dosage and context in the IARC carcinogen lists can lead to agents with health benefits under certain conditions (e.g., solar radiation, red meat consumption, approved drugs) being perceived as universally harmful, discouraging beneficial exposures, behaviors, or treatments. Here, I propose renaming the groups of agents classified by the IARC and adding basic labels to specific agents to improve the accuracy and interpretability of the IARC classification lists. These adjustments do not interfere with the IARC’s objective of identifying potential hazards, are easy to implement, and enhance accuracy and clarity, providing stronger support to guide cancer prevention strategies.

BackgroundThe US EPA considers glyphosate as “not likely to be carcinogenic to humans.” The International Agency for Research on Cancer (IARC) has classified glyphosate as “probably carcinogenic to humans (Group 2A).” EPA asserts that there is no convincing evidence that “glyphosate induces mutations in vivo via the oral route.” IARC concludes there is “strong evidence” that exposure to glyphosate is genotoxic through at least two mechanisms known to be associated with human carcinogens (DNA damage, oxidative stress). Why and how did EPA and IARC reach such different conclusions?ResultsA total of 52 genotoxicity assays done by registrants were cited by the EPA in its 2016 evaluation of technical glyphosate, and another 52 assays appeared in the public literature. Of these, one regulatory assay (2%) and 35 published assays (67%) reported positive evidence of a genotoxic response. In the case of formulated, glyphosate-based herbicides (GBHs), 43 regulatory assays were cited by EPA, plus 65 assays published in peer-reviewed journals. Of these, none of the regulatory, and 49 published assays (75%) reported evidence of a genotoxic response following exposure to a GBH. IARC considered a total of 118 genotoxicity assays in six core tables on glyphosate technical, GBHs, and aminomethylphosphonic acid (AMPA), glyphosate’s primary metabolite. EPA’s analysis encompassed 51 of these 118 assays (43%). In addition, IARC analyzed another 81 assays exploring other possible genotoxic mechanisms (mostly related to sex hormones and oxidative stress), of which 62 (77%) reported positive results. IARC placed considerable weight on three positive GBH studies in exposed human populations, whereas EPA placed little or no weight on them.ConclusionsEPA and IARC reached diametrically opposed conclusions on glyphosate genotoxicity for three primary reasons: (1) in the core tables compiled by EPA and IARC, the EPA relied mostly on registrant-commissioned, unpublished regulatory studies, 99% of which were negative, while IARC relied mostly on peer-reviewed studies of which 70% were positive (83 of 118); (2) EPA’s evaluation was largely based on data from studies on technical glyphosate, whereas IARC’s review placed heavy weight on the results of formulated GBH and AMPA assays; (3) EPA’s evaluation was focused on typical, general population dietary exposures assuming legal, food-crop uses, and did not take into account, nor address generally higher occupational exposures and risks. IARC’s assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. More research is needed on real-world exposures to the chemicals within formulated GBHs and the biological fate and consequences of such exposures.

The International Agency for Research on Cancer: from global evidence to national action.

Cancer prevention

in Lyon, France, we lost a great human being, a staunch advocate for public health, a thorough and delving scientist, and a humanitarian par excellence. Lorenzo Tomatis, MD, above all, was a learned teacher and creative innovator. His accomplishments are legion, and his far-reaching impact on human health, including the well-being of future generations, will be impossible to replace. Tomatis was clearly a true pioneer and admired leader in primary disease prevention. He stands tall among other giants and trailblazers of environmental health science and public health advocacy including Cesare Maltoni, Norton Nelson,

The accumulating epidemiological evidence of elevated cancer risk and mortality in individuals exposed to polychlorinated biphenyls (PCBs) led to their recent classification as human carcinogen by the International Agency for Research on Cancer (IARC) (International Agency for Research on Cancer (IARC), 2015). However, the mechanisms by which PCBs are linked to cancer are still unclear. In this issue, Scinicariello and Buser (Scinicariello, 2015) conducted a study of the association between leukocyte telomere length (LTL) and PCB blood levels in a nationally representative sample of the civilian US adult population using data from the National Health and Nutrition Examination Survey (NHANES). The authors showed that higher PCB blood levels were associated with longer LTL, and hypothesized that there could be a link to PCB-related carcinogenesis. A separate study reported similar relationships between LTL and PCB blood levels in a subset of NHANES participants (Mitro et al., 2015). However, a small study of healthy Koreans (Shin et al., 2010) showed that this relationship was only present at low PCB levels. In contrast, short LTL has been associated with a number of environmental or occupational exposures including particulate matter, black carbon, benzene, toluene, polycyclic aromatic hydrocarbons, N-nitrosamines, pesticides, and lead (reviewed in Zhang et al., 2013), all of which may contribute to PCB blood levels. Telomere shortening in response to chemical exposures may be explained, at least in part, by the induction of an oxidative stress DNA damage response (Zhang et al., 2013). Telomeres, the long (TTAGGG)n nucleotide repeats and an associated protein complex at chromosome ends, are essential for maintaining chromosomal stability. They shorten with each cell division and therefore are markers for cellular replicative capacity, cellular senescence, and aging. Telomere shortening and chromosomal instability has been described at early stages of carcinogenesis, suggesting a role of telomere dysfunction in cancer initiation (Ferguson et al., 2015). Cancer epidemiology studies have shown relationships with short LTL, but differences by cancer site and study design were noted. In a meta-analysis of 27 reports (Wentzensen et al., 2011), short LTL was associated with cancer risk, primarily in case–control studies (OR = 2.9 in case–control studies vs. 1.2 in prospective studies). This suggests that short LTL is a disease marker rather than a risk factor. Recently, a large study linked long LTL to melanoma risk (Iles et al., 2014). The spectrum of cancers associated with long LTL is not clear yet, but suggested to include lung and Non-Hodgkin's lymphoma (NHL). It is of interest that cutaneous melanoma and possibly NHL are the main cancers associated with excess risk in PCBs exposed individuals (International Agency for Research on Cancer (IARC), 2015), suggesting a possible contribution of LTL in PCB-related carcinogenesis. The large sample size, the national representation, and the wealth of collected information NHANES offers are among the strengths of this study. On the other hand, the cross-sectional design restricted its ability to establish a causal inference between LTL, PCB exposure, and cancer risk. The one-time measurement of PCB blood level and LTL may not reflect the full spectrum of the association. Information on the duration and dose of exposure to PCBs would have been useful (reviewed in Zhang et al., 2013) Short-term exposure to ambient particulate matter was associated with long LTL, while longer exposures were associated with short LTL. Exposure dose in relation to LTL was noted in other environmental exposures. For example, exposure to low dose of arsenic resulted in telomerase overexpression and telomere elongation in cord blood cells, while exposure at large doses suppressed telomerase, shortened telomeres, and induced apoptosis. A recent study (Andreotti et al., 2015) evaluating the association between LTL and pesticide exposure suggested a differential effect on LTL in long-term versus recent exposures for certain pesticides. While LTL may present a good surrogate for telomere length in other tissues, it is not clear how good of a surrogate it is for tissues affected by chemical exposures. Measuring telomere length in organs directly affected by PCB exposure, and comparing this to LTL may explain the role telomeres may play in PCB-related carcinogenesis. Also, LTL measurement obtained by quantitative polymerase chain reaction (qPCR) assay may be affected by the cell composition of the sample since telomere length differs by peripheral blood cell subtype. Using a leukocyte cell-type specific TL measurement assay such as flow FISH may provide better insights into such association. Important considerations in epidemiological studies of telomere length are discussed in details elsewhere (Bodelon et al., 2014). In conclusion, the mechanism behind PCB-related carcinogenesis is still unknown. The similarity between cancer sites associated with long LTL, and cancers linked with PCBs provides an interesting hypothesis to test. A large prospective study with serial LTL and PCBs level measurements is required to better understand this relationship.

screen. Chemicals which are shown to be mutagenic in Phase I assays progress to Phase II. In addition, a certain number of chemicals giving negative results in Phase I are committed also to further testing in Phase II, based primarily on known biological activity of structurally related compounds, and on estimated levels of human exposure. Chemicals which are positive mutagens

Transparency in IARC Monographs