Cancer in the Non-Smoking Area

18. December 2007

Tobacco increases the risk of lung cancer like hardly any other factor. Nonetheless - the bronchial carcinoma hits overproportionally many never puffing away on a smoke. Some researchers start believing in a special non-smoker lung cancer.

Worldwide about 1 million dead every year, about 40,000 in Germany. Lung cancer still is one of the most dangerous killers for man. It is number one for men. For women it comes right after breast- and intestinal cancer. Patients have an average chance of only 14% to be still alive five years after the diagnosis of this malicious tumor in their lung.

"It's his own fault. After all those cigarettes!" Often patients not just have to undergo exhausting therapies, but also deal with the scathing judgement of their environment. But even if tobacco increases the risk for lung caner by 20 times, about every fourth case of bronchial carcinoma is a non-smoker. And if the number one source of risk – the ciggy – is not it any more, other factors should be responsible for the development of the cell tumor in non-smokers. Indeed examinations point in the direction that cancer develops differently in non-smokers than it does in nicotine addicts.

Pathfinding in oncogene mutations

One fifth of all lung cancer cases are caused by the small-cell carcinoma which is found almost only in smokers. The adenocarcinoma is the most prevalent cancer in non-smokers and found generally as often as the squamous epithelium-carcinoma, while the "large cell" is found rather rarely. The distribution by sex opens a lot of room for speculations: In general two and a half times more men than women suffer from lung cancer. The ratio reverses in non-smokers. A Swedish study showed just recently, that compared to 20.8 women, just 13.7 men were diagnosed with this tumor. The authors now speculate that women suffer more often from smoking partners and work colleagues than men. But, according to Ali Gazdar of the Texas-University in Dallas, that is not enough to explain the high lung cancer rate among non-smokers.

And the like applies for pollutants or environmentally hazardous substances. The pollution increases the danger to get lung cancer as well. But none of these factors get even close to the relevance of tobacco consumption for the development of a bronchial carcinoma.
So which differences are responsible for the unexpected diagnosis of lung cancer in "teetotallers"? More likely than epidemiologists, gene analyzers appear to be finding the right path. Mutations of the EGFR-gene (Epidermal Growth Factor Receptor) are the first changes in the DNA at all associated with non-smoking. Smokers show significantly less mutations on this oncogene of the tyrosine-kinase receptors. A working group at the Sloan-Kettering Center in New York found this out just last year. The reverse result applies for the oncogene KRAS and the tumor suppressor factor p53 which is more frequently changed in smokers. More differences show in the methylization pattern of the DNA.

Non-smokers survive longer

It seems that non-smokers get the better deal when it comes to the treatment of the tumor. Independent from the progress of the disease, the therapy and comorbidity, they live longer in their fight against the cancer. Studies in Florida and California show decisively improved chances to survive the diagnosis "bronchial carcinoma" for more than five years. Especially the therapy with the EGFR inhibitors appears to be successful with non-smokers. In a retrospective study again, physicians at the Sloan Kettering Center found a four-times higher response rate in the metastasizing adenoma carcinoma. Robert Pirker, oncologists at the general hospital in Vienna emphasized as well during a recent interview the chances resulting from the various manifestations of the tumor: "The data clearly shows that non-smokers react a lot better to the therapy with the new tyrosine-kinase inhibitors than smokers".
But other promising therapies increase life expectancy of lung carcinoma patients as well. Last August, the European Drug Administration approved of the angiogenese-inhibitor Bevacizumab. For the first time, this inhibitor reached a median surviving time of more than a year in a phase III study of a non-small cell bronchial carcinoma.

Genome-map bronchial carcinoma

A few days ago, Nature finally published a "genome-map" of the adenocarcinoma in the lung. 57 genes showed frequent changes or missed completely compared to the controls. Here the gene NKX2.1 seemed of particular interest to the researchers. It codes for a transcription factor, especially changed in the adenocarcinoma influencing the growth of the tumor. The new data could set out the key tracks to finally find a better explanation for the development of lung cancer in non-smokers.

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