An increased risk of lung cancer has been described after tuberculosis (Aoki, 1993). In addition, lung fibrosis from chronic exposure to high levels of fibers and dusts may result in a condition that increases the risk of lung cancer, such as silicosis and asbestosis. Chronic respiratory diseases have been associated with lung cancer risk. Patients with chronic bronchitis and emphysema are at moderately increased risk, which is greater for squamous cell carcinoma, after adjustment for tobacco smoking (Gao et al., 1987; Wu et al, 1995; Mayne et al, 1999). The roles of shared exposures, namely tobacco smoking and chronic inflammation, have not been disentangled. A meta analysis of studies of lung cancer and asthma resulted in a summary RR of 1.8 (95% CI 1.3-2.3) (Santillan et al, 2003); the results were similar when the analysis was restricted to studies that controlled for smoking. Since the evidence is mainly based on case-control studies, recall bias cannot be fully excluded. The risk of lung cancer is increased in patients surviving other tobacco- and lifestyle-related cancers (Li and Hemminki, 2003). Commonality of risk factors, long-term effects of radiotherapy, and increased susceptibility probably interact in the causation of second primary cancers. The effect of chemotherapy and radiotherapy on the risk of a second primary lung cancer has been extensively investigated among long-term survivors of breast cancer, 2% to 9% of whom develop lung cancer (Daly and Costalas, 1999). In an analysis restricted to patients receiving radiotherapy, a clear exposure-response relationship has been shown, together with an interactive effect of tobacco smoking. Several studies have assessed lung cancer risk among regular users of aspirin and other non-steroidal anti-inflammatory drug (NSAID)s. A meta-analysis of eleven studies included in a recent review (Harris et al, 2005) resulted in a pooled RR of 0.75 (95% CI 0.59-0.94). There was however heterogeneity among the different studies, likely due in part to differences in the definition of the exposure. The protective effect was stronger for case-control studies (RR 0.60, 95% CI 0.41-0.89) than cohort studies (RR 0.90, 95% CI 0.74-1.09), suggesting a role for recall bias. In particular, a large cohort study of one million US volunteers did not report a reduction in risk (Thun et al, 1991). Lastly, allergies related conditions such as hay fever and eczema have been shown to be associated with reduced lung cancer risk, although the evidence is not yet conclusive. A joint analysis of these medical conditions can help to clarify their roles in lung carcinogenesis (Castaing M et al, 2005, Wang et al, 2005, Gorlova et al, 2006, Merrill et al 2007)

Objectives

To estimate the risk of lung cancer after the following conditions:

1. tuberculosis, lung fibrosis, chronic obstructive pulmonary disease (possibly separately for chronic bronchitis, emphysema, asthma);
2. a first primary cancer (separately for tobacco- and non tobacco-related cancers);
3. use of aspirin and other NSAID.
4. Hay fevers, eczema and other allergy condition

Methods

Information on medical conditions and use of NSAID will be sought from PI of studies participating in ILCCO. Risk factors will be selected for the pooled analysis if relevant data are available from at least three studies.
Primary data will be requested from PI of the studies, unless these data are already included in the pooled dataset. Quality control checks will be performed and variable distributions will be checked for inconsistencies and anomalies. Problems will be solved in collaboration with the study PI. At the end of data cleaning procedures, the list of risk factors available for analysis will be finalized, based on quality of available information and number of study subjects. The pooled analysis will be conducted by using a two-stage model. Firstly, study-specific results will be generated via logistic or Cox regression; secondly, study-specific estimates will be pooled using a random-effects model, to allow for uncontrolled sources of inter-study variability. Results will also be stratified by geographic region, sex and age, to explore genetic and environmental (e.g., calendar period) effect modifiers. The analysis will be repeated for the major histological types.

Variables Needed

See attached spreadsheet. We are requesting data from all first-degree relatives (parents, offspring, full siblings), regardless of whether or not the relative has had cancer.

Publication Plan

There are 4 potential papers from this project, in line with the 4 objectives. The groups leading this project will each take on a specific set of analysis and be the primary authors responsible for preparing the corresponding manuscript. The authorship of studies contributing the data will follow the ILCCO Authorship Policy.

References

• Aoki K. Excess incidence of lung cancer among pulmonary tuberculosis patients. Jpn J Clin Oncol 1993;23:205-20.
• Daly MB, Costalas J. Breast cancer. In: Neugut AI, Meadows AT, Robinson E (Eds.). Multiple Primary Cancers. Philadephia, Lippincott Williams & Wilkins, 1999, pp. 303-17.
• Gao YT, Blot WJ, Zheng W, Ershow AG, Hsu CW, Levin LI, et al. Lung cancer among Chinese women. Int J Cancer 1987;40:604-9.
• Harris RE, Beebe-Donk J, Doss H, Burr Doss D. Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: A critical review of non-selective COX-2 blockade. Oncol Rep 2005;13:559-83.
• Li X, Hemminki K. Familial and second lung cancers: a nation-wide epidemiologic study from Sweden. Lung Cancer 2003;39:255-63.
• Mayne ST, Buenconsejo J, Janerich DT. Previous lung cancer disease and risk of lung cancer among men and women nonsmokers. Am J Epidemiol 1999;149:13-20.
• Santillan AA, Camargo CA Jr, Colditz GA. A meta-analysis of asthma and risk of lung cancer. Cancer Causes Control 2003;14:327-34.
• Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 1991;325:1593-6.
• Wu AH, Fontham ETH, Reynolds P, Greenberg RS, Buffler P, Liff J, et al. Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States. Am J Epidemiol 1995;141:1023-32.
• Castaing M, Youngson J, Zaridze D, Szeszenia-Dabrowska N, Rudnai P, Lissowska J, Fabiánová E, Mates D, Bencko V, Foretova L, Navratilova M, Janout V, Fletcher T, Brennan P, Boffetta P. Is the risk of lung cancer reduced among eczema patients? Am J Epidemiol. 2005 Sep 15;162(6):542-7
• Gorlova OY, Zhang Y, Schabath MB, Lei L, Zhang Q, Amos CI, Spitz MR. Never smokers and lung cancer risk: a case-control study of epidemiological factors. Int J Cancer. 2006 Apr 1;118(7):1798-804
• Wang H, Diepgen TL. Is atopy a protective or a risk factor for cancer? A review of epidemiological studies. Allergy. 2005 Sep;60(9):1098-111. Review.
• Merrill RM, Isakson RT, Beck RE. The association between allergies and cancer: what is currently known? Ann Allergy Asthma Immunol. 2007 Aug;99(2):102-16