Re: Translocations and Lung Cancer

Steve,

The genetics of lung cancer is an extremely complex area which is the 
target of much current research.  Your question is difficult to answer 
because there is no clear picture yet showing which of the many genetic 
alterations found in lung cancer are early changes, and therefore likely to 
be involved in CAUSING the cancer, and which are changes which occur as a 
RESULT of the growth of the tumor.  Since you are asking about 
susceptibility, you’re interested in the very first genetic changes which 
occur which increase the likelihood of developing a tumor.  These early 
changes probably don’t result in tumor growth themselves, and other genetic 
alterations must accumulate before cancer develops.

The karyotype of lung cancer cells, or the picture of the chromosomes 
within the cells, is usually very abnormal.  Instead of the normal 
complement of 23 pairs of chromosomes, lung cancer cells often have 
translocations as well as extra copies of whole or fragmented chromosomes, 
and all or portions of some chromosomes deleted (all within the same cell).  
By examining the karyotype of many different lung cancer cell lines, 
researchers have tried to identify chromosomal alterations which occur the 
most frequently.  These changes may represent the earliest mutations that 
are necessary for tumor formation to occur.  For instance, the most common 
chromosomal alteration observed in lung cancer involves deletion of a small 
region of chromosome 3, which is seen in 70-100% of tumors which have been 
analyzed.  Translocations of various chromosomes are observed, but no 
specific translocation has been identified at a high frequency in lung 
cancer.  It is certainly conceivable that a translocation which involved 
the critical region of chromosome 3 would increase susceptibility to lung 
cancer, but to my knowledge this has not been reported in the scientific 
literature.

Even the area of lung cancer susceptibility is complicated and unclear.  
The major cause of lung cancer is cigarette smoking, accounting for 90% of 
lung cancer cases. But since only about 15% of smokers develop lung cancer, 
it is thought that there is a subset of the population that is more 
susceptible to developing cancer in response to tobacco smoke.  One of the 
best ways to identify genes that increase susceptibility to cancer is in 
families, such as you may have heard about for breast cancer.  There are a 
very few instances of families where lung cancer susceptibility seems to be 
inherited, and the analysis of these cases is almost always complicated by 
the fact that members of the family smoke or are exposed to passive smoke.

Now that you have the long answer, the short answer is we don’t know, but 
keep your eye on the news. Research in this area is moving so quickly these 
days it’s almost impossible to keep up, even for those of us who study lung 
cancer.

Sharon Shriver