The complexity of tobacco smoke leads to some confusion about the mechanisms by which it causes lung cancer. Among the multiple components of tobacco smoke, 20 carcinogens convincingly cause lung tumors in laboratory animals or humans and are, therefore, likely to be involved in lung cancer induction. Of these, polycyclic aromatic hydrocarbons and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone are likely to play major roles. This review focuses on carcinogens in tobacco smoke as a means of simplifying and clarifying the relevant information that provides a mechanistic framework linking nicotine addiction with lung cancer through exposure to such compounds. Included is a discussion of the mechanisms by which tobacco smoke carcinogens interact with DNA and cause genetic changes--mechanisms that are reasonably well understood--and the less well defined relationship between exposure to specific tobacco smoke carcinogens and mutations in oncogenes and tumor suppressor genes. Molecular epidemiologic studies of gene-carcinogen interactions and lung cancer--an approach that has not yet reached its full potential--are also discussed, as are inhalation studies of tobacco smoke in laboratory animals and the potential role of free radicals and oxidative damage in tobacco-associated carcinogenesis. By focusing in this review on several important carcinogens in tobacco smoke, the complexities in understanding tobacco-induced cancer can be reduced, and new approaches for lung cancer prevention can be envisioned.

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Tobacco Smoke Carcinogens and Lung Cancer

The devastating link between tobacco products and human cancers results from a powerful alliance of two factors - nicotine and carcinogens. Without either one of these, tobacco would be just another commodity, instead of being the single greatest cause of death due to preventable cancer. Nicotine is addictive and toxic, but it is not carcinogenic. This addiction, however, causes people to use tobacco products continually, and these products contain many carcinogens. What are the mechanisms by which this deadly combination leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms?

Tobacco carcinogens, their biomarkers and tobacco-induced cancer.

Acute myeloid leukaemia (AML) is a disorder characterized by a clonal proliferation derived from primitive haematopoietic stem cells or progenitor cells. Abnormal differentiation of myeloid cells results in a high level of immature malignant cells and fewer differentiated red blood cells, platelets and white blood cells. The disease occurs at all ages, but predominantly occurs in older people (>60 years of age). AML typically presents with a rapid onset of symptoms that are attributable to bone marrow failure and may be fatal within weeks or months when left untreated. The genomic landscape of AML has been determined and genetic instability is infrequent with a relatively small number of driver mutations. Mutations in genes involved in epigenetic regulation are common and are early events in leukaemogenesis. The subclassification of AML has been dependent on the morphology and cytogenetics of blood and bone marrow cells, but specific mutational analysis is now being incorporated. Improvements in treatment in younger patients over the past 35 years has largely been due to dose escalation and better supportive care. Allogeneic haematopoietic stem cell transplantation may be used to consolidate remission in those patients who are deemed to be at high risk of relapse. A plethora of new agents - including those targeted at specific biochemical pathways and immunotherapeutic approaches - are now in trial based on improved understanding of disease pathophysiology. These advances provide good grounds for optimism, although mortality remains high especially in older patients.

Acute myeloid leukaemia.

King’s College Hospital, St Mary’s Hospital, Barts and The London Hospital, London, Birmingham Children’s Hospital, Birmingham, Barts and The London School of Medicine and Dentistry, St George’s Hospital, London, Queen Elizabeth Hospital, King’s Lynn, Norfolk, Ashford Hospital, Middlesex, London, Patient representative, St Helier Hospital, Carshalton, Surrey, Royal Bournemouth Hospital, Dorset, Chesterfield Royal Hospital, Derbyshire, and Manchester Royal Infirmary, Manchester, UK.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.2009.07842.x

Guidelines for the diagnosis and management of aplastic anaemia

Laboratory research has shown that numerous environmental pollutants cause mammary gland tumors in animals; are hormonally active, specifically mimicking estrogen, which is a breast cancer risk factor; or affect susceptibility of the mammary gland to carcinogenesis An assessment of epidemiologic research on these pollutants identified in toxicologic studies can guide future research and exposure reduction aimed at prevention The PubMed database was searched for relevant literature and systematic critical reviews were entered in a database available at URL: wwwsilentspringorg/sciencereview and URL: wwwkomenorg/environment (accessed April 10, 2007) Based on a relatively small number of studies, the evidence to date generally supports an association between breast cancer and polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in conjunction with certain genetic polymorphisms involved in carcinogen activation and steroid hormone metabolism Evidence regarding dioxins and organic solvents is sparse and methodologically limited but suggestive of an association Methodologic problems include inadequate exposure assessment, a lack of access to highly exposed and unexposed populations, and a lack of preclinical markers to identify associations that may be obscured by disease latency Among chemicals identified in toxicologic research as relevant to breast cancer, many have not been investigated in humans The development of better exposure assessment methods is needed to fill this gap In the interim, weaknesses in the epidemiologic literature argue for greater reliance on toxicologic studies to develop national policies to reduce chemical exposures that may be associated with breast cancer Substantial research progress in the last 5 years suggests that the investigation of environmental pollutants will lead to strategies to reduce breast cancer risk

/pdf/environmental-pollutants-and-breast-cancer-epidemiologic-2rx280n6y1.pdf

Environmental pollutants and breast cancer: epidemiologic studies.

A large cohort study of 74,828 benzene-exposed and 35,805 unexposed workers employed between 1972 and 1987 in 12 cities in China were followed to determine mortality from all causes and the incidence of lymphohematopoietic malignancies and other hematologic disorders. Benzene-exposed study subjects were employed in a variety of occupations, including painting, printing, and the manufacture of footwear, paint, and other chemicals. All-cause mortality was similar in the benzene-exposed and unexposed comparison group. Statistically significant excess deaths were noted among benzene-exposed subjects for leukemia (RR = 2.3, 95% CP 1.1-5.0), malignant lymphoma (RR = 4.5, 95% CI: 1.3-28.4), and nonneoplastic diseases of the blood (RR = 95% CP 2.5-infinity), and a marginally significant excess was noted for lung cancer (RR = 1.4, 95% CI: 1.0-2.0). Risk was significantly elevated for the incidence of all lymphohematopoietic malignancies (RR = 2.6, 95% CI: 1.5-5.0), malignant lymphoma (RR = 3.5, 95% CI: 1.2-14.9), and leukemia (RR = 2.6, 95% CI.. 1.3-5.7). Among the leukemia subtypes, only acute myelogenous leukemia (AML) incidence was significantly elevated (RR = 3.1, 95% CI: 1.2-10.7), although nonsignificant excesses were also noted for chronic myelogenous leukemia (CML) (RR = 2.6, 95% CI: 0.7-16.9) and lymphocytic leukemias (RR = 2.8, 95% CI.. 0.5-54.5). Significant excesses were found for aplastic anemia (RR = infinity, 95% CI: 2.2-co) and myelodysplastic syndrome (RR = infinity, 95% CI: 1.7-infinity). Employment in benzene-associated occupations in China is associated with a wide spectrum of myelogenous and lymphocytic malignant diseases and related disorders. Investigations continue to assess the nature of these associations.

A cohort study of cancer among benzene-exposed workers in China: overall results.

An expanded cohort study of 74,828 benzene-exposed and 35,805 unexposed workers were followed during 1972 to 1987, based on a previous study in 12 cities in China. A small increase was observed in total cancer mortality among benzene-exposed compared with unexposed Workers (relative risk [RR] = 1-2). Statistically significant excesses were noted for leukemia (RR = 2.3), malignant lymphoma (RR = 4.5), and lung cancer (RR = 1.4). When risks were evaluated by leukemia subtype, only acute myelogenous leukemia was significantly elevated (RR = 3.1), although nonsignificant excesses were also noted for chronic myelogenous leukemia (RR = 2.6) and acute lymphocytic leukemia (RR = 2.3). A significant excess was also found for aplastic anemia. 19 refs., 5 tabs.

https://www.jstor.org/stable/info/3433187

An expanded cohort study of cancer among benzene-exposed workers in China

A large cohort of 74,828 benzene-exposed and 35,805 nonexposed workers employed between 1972 and 1987 in 12 cities in China was followed to determine mortality from all causes. Benzene-exposed study subjects were employed in a variety of occupations including coating applications, and rubber, chemical, and shoe production. Mortality was slightly increased among workers with greater cumulative exposure to benzene (ptrend < 0.05), but this excess was largely due to cancer deaths (ptrend < 0.01). Deaths due to lymphatic and hematopoietic malignancies (ptrend = 0.01) and lung cancer (ptrend = 0.01) increased with increasing cumulative exposure to benzene. Investigations continue to relate benzene exposure to specific lymphatic and hematopoietic malignancies and other causes of death.

Mortality among benzene-exposed workers in China

전 세계적으로 사회가 발전하고 뉴미디어가 부상하면서 많은 강연 프로그램이 끊임없이 관중들에게 선보이고 있다. 2000년대 중국에서는 ‘기파설(奇葩说)’ ‘세계 청년설(世界⻘年说)’ 프로그램이 등장했고, 2012년 시작한 ‘개강이야(开讲啦)’은 중국 최초로 청년들을 위한 공개 강연으로서 참신한 아이디어의 물결을 일으켰다. 이 프로그램은 중국의 청소년들이 주체적으로 성장하고 어려움에 처해도 의연하게 대처해야 함을 일깨워주었다. 한편, 이 프로그램에서는 사회자, 게스트, 참가자 모두 별다른 제한 없이 자유롭게 이야기함으로써 ‘독립적이고 자유로운 이념’을 잘 표현하고 있다. 1929년 진인각(陈寅恪) 선생이 내세운 ‘독립의 정신, 자유의 사상(独⽴的精神, 自由的思想)’은 오늘날까지 학문과 그 실천의 모범으로 추앙받고 있다. 본고는 왜 이 이념이 오늘까지 계속 존경받고 있고, 어떤 매력이 있는 지를 진인각(陈寅恪) 선생의 《给科学院答复》을 분석하여 그 해답을 찾아보고자 한다. 본고는 수사학적 관점에서 글 쓸 당시의 수사적 상황, 논거 찾기, 배열, 풍격과 수사법 등 다각도로 분석하였다. 

Wan You Zhang

Papers

A cohort study of cancer among benzene-exposed workers in China: overall results.

An expanded cohort study of cancer among benzene-exposed workers in China

Mortality among benzene-exposed workers in China

A Rhetoric Analysis of Chen Yinke"s “Spirit of Independence, Ideas of Freedom” - Reply to the Academy of Sciences -