According to data from the National Cancer Institute, the incidence of lung cancer in males between 1975 and 2007 has decreased from 9% to 7.2 %. For females, however, the rates have nearly doubled from 2.4% to 5.5%.1 In 2013, there are expected to be 228,190 new lung cancer cases, and 26% of cancer-related deaths in females will come from that group.2,3 The data shows that the rates of women with lung cancer are steadily increasing.
While smokers are at high risk of developing lung cancer, nonsmokers—particularly nonsmoking women—have their own set of risk factors that may contribute to lung cancer. A number of studies have explored various environmental risk factors that have contributed to the increasing incidence, including:
- Second hand smoke2
- Radon Gas (comes from soil and building materials and is known as the second leading cause of lung cancer)2
- Chemicals (eg, air pollution, diesel exhaust, paint)2
- Rubber manufacturing, paving, roofing and chimney sweeping2
- History of tuberculosis2
- Cooking oil fumes4
There may be a connection between lung cancer and estrogen levels, based on a recent study that has shown that lung cells make 17β estradiol within murine lung tissue. The aim of the study was to identify early genetic changes in the cells before the tumor is formed, including how estrogen may affect the development of lung tumors. The researchers looked at the lung cells of female animals that were exposed to tobacco smoke, and found 10 differential expressions of the genes around CYP1b1, a phase 1 enzyme, that helps to break down tobacco smoke and estrogen.
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Detection of estrogen conjugates within the lungs, as well as estrogen-associated DNA adducts, is a promising tool to clarify the mechanism by which estrogen causes lung carcinogens.5 CYP1b1 also causes estrogen to convert to an active form of estradiol, which can cause DNA mutation and activate cancer-causing agents in tobacco. For women, this estrogen pathway can be harmful because of elevated levels of estrogen, particularly before menopause. The use of medicines that affect estrogen levels, such as hormone replacement therapy and birth control, also puts women at a higher risk for developing lung cancer.1
In women, body chemicals are metabolized differently than in men, and female genes are more susceptible to harm from tobacco smoke.6 A study by Luo et al revealed that postmenopausal women treated with insulin have a significantly higher risk of lung cancer when compared to women without diabetes or insulin treatment.7
Hyperglycemia (high blood sugar) activates the polyol pathway, which increases the sorbitol that can result in cellular stress and a decrease in the intracellular antioxidant defenses. Therefore, lung function can be decreased in diabetic patients who do not have sufficient control over their glucose levels. The study concluded that patients with type 2 diabetes who were prescribed both sulfonylurea and exogenous insulin have a higher risk of cancer-related death compared to patients that were only prescribed metformin.7
Another study found a link between the mutation of the epidermal growth factor receptor tyrosine kinase (EGFR TK) in never-smokers and the progression of NSCLC. Gene mutations were more common in nonsmokers and females.5 NSCLC is often treated with combination cytotoxic chemotherapy. The receptor tyrosine kinases serve as cell signaling mediators by receptor-specific ligands. The most prevalent genes in smokers are TP53 gene, KRAS gene, or deletion of the short arm of chromosomes. No valid data exists that can explain why EGFR mutation is associated with nonsmoking. According to the results of the study, the team has assumed that EGFR mutations are caused by carcinogens.
Overall, there is a need for additional research to validate these data points. Researchers are now finding medications that can be used in patients for specific gene mutations. Attention is being given to AP26113 for patients who have an NSCLC-positive specific mutation in the EGFR gene.8 More research on gene mutation specific therapies is needed to help decrease the incidence of lung cancer in women, specifically in nonsmokers.
References
1. Wang S. Lung cancer in Women in the Rise. Wall Street Journal. June 8th 2010. Accessed: http://online.wsj.com/article/SB10001424052748704764404575287081156194368.html.
2. American Cancer Society. Cancer Facts & Figures 2013. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/ACSPC-036845. Accessed April 2, 2013.
3. Siegel R, Naishadham D, et al. Cancer Statistics 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30.
4. Kosaka T, Yatabe Y, Endoh H, et al. Mutation of epidermal growth factor receptor gene in lung cancer: Biological and clinical implications. Cancer Res. 2004 Dec 15;64(24):8919-8923.
5. Meireles SI, Esteves GH, Hirata R Jr,, et al. Early changes in gene expression induced by tobacco smoke: Evidence for importance of estrogen within lung tissue. Cancer Prev Res (Phila). 2010 Jun;3(6):707-717.
6. Women and Lung Cancer. Cancer.Net. http://www.cancer.net/all-about-cancer/cancernet-feature-articles/cancer-screening-and-prevention/women-and-lung-cancer. Accessed March 5, 2013.
7. Luo J, Chlebowski R, Wactawski-Wende J, et al. Diabetes and lung cancer among postmenopausal women. Diabetes Care. 2012 Jul;35(7):1485-1491.
8. Ariad lung cancer drug targeted for specific gene mutation shrinks tumors in small trial. http://medcitynews.com/2012/09/ariad-lung-cancer-drug-targeted-for-specific-gene-mutation-shrinks-tumors-in-small-trial/. Published September 29, 2012. Accessed April 2, 2013.
