April 20, 2009
Some Good News In The Fight Against Lung Cancer
By Michael D. Shaw
We hear a lot about breast and prostate cancer—as we should—since they are the most diagnosed forms of the disease in women and men respectively. However the biggest killer among the cancers, for both sexes, is lung cancer.
According to American Cancer Society estimates for 2008, 215,020 new cases of lung cancer in the U.S. will be diagnosed and 161,840 deaths due to the disease will occur. The National Cancer Institute figures that approximately one out of every 14 men and women in the U.S. will be diagnosed with cancer of the lung or airways at some point in their lifetime.
It is well known that cigarette smoking is the major risk factor for lung cancer, showing up in about 90% of all cases. But what about that other ten percent?
For these, environmental causes are often proffered, the primary one being radon; but radon etiology is based on models utilizing the controversial linear no-threshold assumption, as it was applied to sketchy data on a small group of uranium miners more than 50 years ago. Asbestos exposure is surely a risk factor, but asbestos workers who also smoke have a risk that is 50 to 90 times greater than nonsmokers.
As to secondhand smoke, studies posit a 24% increased risk factor for these individuals, but figures on morbidity and mortality are mostly based on modeling—owing to the inherent difficulties of quantifying such concepts.
Beyond discerning the ten percent cohort, it has long been suggested that a strong genetic component also exists for lung cancer. For example, a widely-cited 2005 study from the Journal of the American Medical Association found that “Smokers with a family history of early-onset lung cancer in a first-degree relative had a higher risk of developing lung cancer with increasing age than smokers without a family history.”
The authors of that study added: “Family history assessment should be included when evaluating smokers or those presenting with symptoms consistent with lung disease.”
Family history, though, has some disadvantages. If smoking causes 90% of all lung cancer cases, and all your relatives smoked, and several did get lung cancer, what does that mean to you if you don’t smoke? Good question. A far better parameter than family history would be a genetic marker, of course. Imagine if you could be tested for a genetic predisposition to lung cancer!
Based on work recently published by University of Cincinnati researcher Marshall Anderson and his collaborators, a specific lung cancer susceptibility gene has been identified in humans. The paper, appearing in the April 15, 2009 issue of Clinical Cancer Research, is entitled “Fine Mapping of Chromosome 6q23-25 Region in Familial Lung Cancer Families Reveals RGS17 as a Likely Candidate Gene.”
The study applied the technique of “fine mapping” to biological samples collected from several multi-generational families, each with five or more members affected by lung cancer. Fine-mapping means that the search for a particular genetic element is confined to a smaller locus on the chromosome.
Harvard professor David Christiani, who was not directly involved in this effort, commented that:
“This study represents a significant contribution to our understanding of lung cancer susceptibility and is another step toward to the goal of preventive medicine. The authors undertook a daunting challenge of performing a family-based study of lung cancer in an effort to identify specific causal genes.”
Anderson himself noted that “Understanding of how the RGS17 gene impacts cancer development could change clinical diagnosis and treatment as radically as discovery of the breast cancer genes (BRCA1 and BRCA2) did. A proven genetic test could help us identify people at risk before the disease progresses.”
This is significant, when you consider that 25% percent of lung cancer patients experience no early symptoms, and are first diagnosed via routine chest X-rays or CT scans. Even more scary is that some people can progress into advanced stages of the disease, with few or no obvious symptoms.
Anderson added that: “What was most interesting is that this same gene was over-expressed in 60 percent of the samples from non-hereditary lung tumors. This suggests that perhaps epigenetic factors [regulation of the expression of gene activity without alteration of genetic structure] may be contributing to abnormal genetic development.”
The group plans to examine how environmental factors might affect familial cancer development.