Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review

Tobacco use is considered the single most important man-made cause of cancer that can be avoided. The evidence that nicotine is involved in cancer development is reviewed and discussed in this paper. Both tobacco smoke and tobacco products for oral use contain a number of carcinogenic substances such as polycyclic hydrocarbons (PAH) and tobacco-specific N-nitrosamines (TSNA) which undoubtedly contribute to tobacco related cancer. Recent studies have shown that nicotine can affect several important steps in the development of cancer, and suggest that it may cause aggravation and recurrence of the disease. TSNA may be formed from nicotine in the body. The role of nicotine as the major addictive component of tobacco products may have distracted our attention from toxicological effects on cell growth, angiogenesis and tumor malignancy. Effects on cancer disease are important aspects in the evaluation of possible long-term effects from sources of nicotine, such as e-cigarettes and products for nicotine replacement therapy (NRT), which both have a potential for life-long use

Evidence of carcinogenicity in humans of water-soluble nickel salts

<p>Abstract</p> <p>Background</p> <p>Increased risks of nasal cancer and lung cancer in nickel refiners have been investigated scientifically and discussed since they were detected in the 1930s. Nickel compounds are considered to be the main cause of the cancer excess. Parts of the nickel producing industry and their consultants oppose the classification of water-soluble nickel salts as human carcinogens, and argue that the risk in exposed workers should be ascribed to other occupational exposures and smoking.</p> <p>Discussion</p> <p>Respiratory cancer risks in Welsh, Finnish, and Norwegian nickel refiners add to the evidence of carcinogenicity of water-soluble nickel. In Norwegian refiners, the first epidemiological study in 1973 identified high risks of lung cancer and nasal cancer among long-term electrolysis workers. Risk analyses based on exposure estimates developed in the 1980s supported the view that water-soluble nickel compounds were central in the development of cancer. Recently, new exposure estimates were worked out for the same cohort based on personal monitoring of total nickel and chemical determination of four forms of nickel. Additional data have been collected on life-time smoking habits, and on exposure to arsenic, asbestos, sulphuric acid mists, cobalt, and occupational lung carcinogens outside the refinery. After adjustment for these potential confounding exposures in case-control analyses, the risk pattern added to the evidence of an important role of water-soluble nickel compounds as causes of lung cancer. These Norwegian cancer studies rely on national Cancer Registry data, considered close to complete from 1953 onwards; and on National Population Register data continuously updated with mortality and emigration. Canadian mortality studies--perceived to offer the strongest support to the industry position not to recognise carcinogenicity of water-soluble nickel--appear to suffer from limitations in follow-up time, loss to follow-up, absence of risk analysis with individual exposure estimates, no confounder control, and a likely underestimation of cancer mortality.</p> <p>Conclusions</p> <p>Rejection to recognise water-soluble nickel as a human carcinogen seems to contradict material epidemiological evidence that demonstrates a strong association between water-soluble nickel compounds and risks of lung cancer and nasal cancer. Independent international scientific bodies have classified nickel compounds as carcinogenic to humans, inclusive of water-soluble nickel.</p

Variation in Nordic Work-Related Cancer Risks after Adjustment for Alcohol and Tobacco

Background: Alcohol and tobacco strongly increases the risk of cancers of the tongue, mouth, pharynx, larynx, and oesophagus, and are also established risk factors for cancer of the liver, colon, and rectum. It is well documented that these habits are unequally distributed among occupational groups. Most occupational cohort studies lack information on these potentially important confounders, and may therefore be prone to bias. Aim: The aim of the study is to present Nordic standardized incidence ratios (SIRs) for alcohol and tobacco related cancer by occupation, after adjustment for alcohol and tobacco, and to compare to the unadjusted SIRs. Material and Methods: The study is based on the Nordic Occupational Cancer (NOCCA) database. We used confirmatory factor analysis models for simultaneous analysis of the cancer sites related to alcohol and tobacco, to obtain factors that allow for computation of adjusted expected numbers from the reference rates. We then calculated adjusted SIRs for the relevant cancer sites for each occupation. Results: For some occupations and cancers, the changes of risk estimates were striking, from significantly high to significantly low and vice versa. Among Nordic farmers, unadjusted SIRs for cancer of the mouth and oesophagus were 0.56 (95% confidence interval (CI) 0.51-0.61) and 0.67 (CI 0.63-0.70), respectively. After adjustment, estimates changed to 1.10 (CI 1.01-1.21) and 1.16 (CI 1.10-1.22). Unadjusted SIR for pharynx cancer among wood workers was 0.83 (CI 0.75-0.91), adjusted SIR was 1.14 (CI 1.03-1.25). For larynx cancer, results in the opposite direction were seen: unadjusted SIR for economically inactive was 1.38 (CI 1.31-1.46) while the adjusted SIR was 0.91 (CI 0.86-0.96). Conclusions: Adjustment for the latent indicators of alcohol and tobacco consumption changed risk estimates for several occupations, gave a less confounded description of risk, and may guide in the identification of true risk factors.Peer reviewe

A protocol for prospective studies 5-hydroxyvitamin D, leptin and b ass index in relation to cutaneou elanoma incidence and survival

Introduction The incidence and mortality rates of cutaneous melanoma (CM) are increasing among fai skinned populations worldwide. Ultraviolet radiation s the principal risk factor for CM, but is also the mai source of 25-hydroxyvitamin D (25(OH)D), which has associated with reduced risk and better prognosis of cancer types. However, both low and high 25(OH)D l have been associated with increased risk of CM. Obe as measured by body mass index (BMI) is associated risk of several cancers and has also been suggested risk factor for CM, and may also be related to insuffi 25(OH)D and/or high leptin levels. Moreover, contract CM diagnosis has been associated with increased ri developing second cancer. We aim to study whether prediagnostic serum levels of 25(OH)D, high prediag evels of BMI and high serum leptin levels influence ncidence, Breslow thickness and CM mortality, and second cancer and survival after a CM diagnosis. Methods and analysis Cohort and nested case–co studies will be carried out using the population-base Janus Serum Bank Cohort (archival prediagnostic se BMI, smoking and physical activity), with follow-up fr 1972 to 2014. Additional data will be received from t Cancer Registry of Norway, the national Cause of De Registry, Statistics Norway (education and occupatio and exposure matrices of UVR. Time-to-event regres models will be used to analyse the cohort data, whil he nested case–control studies will be analysed by conditional logistic regression. A multilevel approach be applied when incorporating group-level data. Ethics and dissemination The project is approved he Regional Committee for Medical Research Ethics and is funded by the Norwegian Cancer Society. Res will be published in peer-reviewed journals, at scient conferences and in the news media

Anthropometric Factors and Cutaneous Melanoma: Prospective Data from the Population-based Janus Cohort

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking status. During a mean follow-up of 27 years, 3,000 incident CM cases were identified. In men, CM risk was positively associated with body mass index, body surface area (BSA), height and weight (all ptrends \u3c 0.001), and the exposure-response curves indicated an exponential increase in risk for all anthropometric factors. Weight loss of more than 2 kg in men was associated with a 53% lower risk (HR 0.47, 95% CI: 0.39, 0.57). In women, CM risk increased with increasing BSA (ptrend50.002) and height (ptrend \u3c 0.001). The shape of the height- CM risk curve indicated an exponential increase. Our study suggests that large body size, in general, is a CM risk factor in men, and is the first to report that weight loss may reduce the risk of CM among men

Prediagnostic Serum Organochlorine Concentrations and Metastatic Prostate Cancer: A Nested Case–Control Study in the Norwegian Janus Serum Bank Cohort

BackgroundOrganochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern.ObjectivesWe conducted a nested case–control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway.MethodsSera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression.ResultsMetastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but nonsignificant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log–transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02).ConclusionsOur study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer.CitationKoutros S, Langseth H, Grimsrud TK, Barr DB, Vermeulen R, Portengen L, Wacholder S, Beane Freeman LE, Blair A, Hayes RB, Rothman N, Engel LS. 2015. Prediagnostic serum organochlorine concentrations and metastatic prostate cancer: a nested case–control study in the Norwegian Janus Serum Bank cohort. Environ Health Perspect 123:867–872; http://dx.doi.org/10.1289/ehp.140824

Carcinogenicity of cobalt, antimony compounds, and weapons-grade tungsten alloy

The complete evaluation of the carcinogenicity of cobalt, antimony compounds, and weapons-grade tungsten alloy will be published in Volume 131 of the IARC Monographs.[Excerpt] In March, 2022, a Working Group of 31 scientists from 13 countries met remotely at the invitation of the International Agency for Research on Cancer (IARC) to finalise their evaluation of the carcinogenicity of nine agents: cobalt metal (without tungsten carbide or other metal alloys), soluble cobalt(II) salts, cobalt(II) oxide, cobalt(II,III) oxide, cobalt(II) sulfide, other cobalt(II) compounds, trivalent antimony, pentavalent antimony, and weapons-grade tungsten (with nickel and cobalt) alloy. For cobalt metal and the cobalt compounds, particles of all sizes were included in the evaluation. These assessments will be published in Volume 131 of the IARC Monographs.1 Cobalt metal and soluble cobalt(II) salts were classified as “probably carcinogenic to humans” (Group 2A) based on “sufficient” evidence for cancer in experimental animals and “strong” mechanistic evidence in human primary cells. Cobalt(II) oxide and weapons-grade tungsten alloy were classified as “possibly carcinogenic to humans” (Group 2B) based on “sufficient” evidence in experimental animals. Trivalent antimony was classified as “probably carcinogenic to humans” (Group 2A), based on “limited” evidence for cancer in humans, “sufficient” evidence for cancer in experimental animals, and “strong” mechanistic evidence in human primary cells and in experimental systems. Cobalt(II,III) oxide, cobalt(II) sulfide, other cobalt(II) compounds, and pentavalent antimony were each evaluated as “not classifiable as to its carcinogenicity to humans” (Group 3).[...