Second hand smoke, age of exposure and lung cancer risk☆
Introduction
Lung cancer is the leading cause of cancer death for both men and women in the United States. Past studies have demonstrated the association between active cigarette smoking (mainstream smoke, MSS) or second hand smoke (SHS) exposure and the risk of adult non-small cell lung cancer (NSCLC). However, less is known about the effect of the age of exposure, particularly to SHS, on the risk of NSCLC [1], [2], [3]. Most studies [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18] have focused on paternal and maternal smoking during pregnancy and the effect on childhood illnesses and cancers in general or more recently the risk of lung cancer for non-smoking women exposed to tobacco smoke during childhood [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]. Very few studies [19], [22], [29], [30] have focused on the effect of the period of exposure relevant for lung cancer development while also assessing the significance of lifetime exposure by location.
The lung continues to grow from birth to adulthood [31] and most lung growth is over by age 18 [32], [33], [34], but lung volume continues to expand to 25, suggesting additional growth may occur [35], [36], [37], [38], [39]. Exposure of target organs to carcinogens during periods of rapid cell division or childhood is known to increase the risk of cancer and elevated exposure to carcinogens has been associated with higher levels of both DNA-adducts and somatic aberrations in cancer cells and may lead to genetic abnormalities that result in the development into cancer [40], [41].
SHS consists of emissions from cigarettes, pipes and cigars, as well as exhaled materials from MSS, which contains several chemicals including over 50 known carcinogens [40], [42], [43]. The concentrations of benzol(a)pyrene, toluene, dimethylnitrosamines in SHS is much higher than in MSS, and the smaller particles in SHS are more likely to be deposited in the lung. SHS may induce DNA-adducts, sister chromosome exchange [44], oxidative DNA damage [45], [46], and increased number of p53 mutations in lung cancer [47], [48], suggesting a similar etiologic mechanism for cases exposed to SHS and to MSS.
SHS exposure may occur at home (including childhood exposure from parents/other family members and exposure from spouse/family members in adulthood), at work (occupational exposure), and at leisure (exposure at public places other than work). Due to public health education and as a result of legislation in several developed countries, exposure to second hand smoke is declining at work and public places but direct marketing to younger populations by tobacco companies has contributed to continued high exposure among youths [49], [50], [51], [52]. The intensity or frequency of exposure in work places has been noted to be generally higher than that of at home or leisure places [53], and results from a previous study has suggested that SHS exposure at work places may have a stronger effect on NSCLC risk than exposure at home or at leisure places [54].
We hypothesize that after adjusting for active cigarette smoking, if the SHS exposure took place during the critical period of growth, i.e. in the earlier part of life (0–25 years of age) the risk of lung cancer is greater compared to an exposure occurring after age 25.
Section snippets
Study population
This study was reviewed and approved by the Institutional Review Boards of the Massachusetts General Hospital and the Harvard School of Public Health. The study population of 1669 cases and 1263 controls is derived from a large case–control study evaluating the molecular epidemiology of lung cancer, which began in 1992 at the Massachusetts General Hospital (MGH). Eligible cases included any person over the age of 18 years, with a diagnosis of primary lung cancer. An MGH lung pathologist
Patient characteristics
There were a total of 1669 cases and 1263 controls. The distribution of demographic and clinical characteristics by smoking status is summarized in Table 1. Overall median age (standard deviation) was 62 years [12], males were 49%; 604 (21%) non-smokers, 1464 (50%) ex-smokers, 864 (29%) current smokers; median pack–years (standard deviation) for ex- and current smokers 39 [37]. Patients with early stage (stages I and II) numbered 803 (50%), with adenocarcinoma 698 (42%), squamous 339 (21%) and
Discussion
Previous studies of biochemical markers of exposure and toxicological studies, confirm that there is a causal association between the risk of NSCLC and exposure to SHS (2). Similar conclusions have been reached by past summary scientific reports [43], [55]. We suggest further that subjects first exposed before age 25 have a higher lung cancer risk compared to those for whom first exposure occurred after age 25 years. Consistent results are seen in our study for different smoking categories,
Conflict of interest statement
None.
Acknowledgements
The authors gratefully acknowledge the assistance of Linda Lineback, Barbara Bean, Andrea Shafer, Jessica Shin, Jeanne Jackson and Andrea Solomon for patient recruitment and data collection; Lucy Ann Principe, Salvatore V. Mucci, and Richard Rivera-Massa for data entry.
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NIH Grants: CA74386 and ES00002, Flight Attendant Medical Research Institute.
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These authors contributed equally to this work.