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Gene is linked to lung cancer development in never-smokers
Date:3/21/2010

two more GWAS scans in independent populations -- 328 never smoker lung cancer patients and 407 controls at MD Anderson Cancer Center, and 92 never smoker lung cancer patients and 161 controls at Harvard University. From this, the search was narrowed to just two hits. Both of these hits were adjacent to each other on the same gene, which the researchers then identified as a variant of GPC5.

In the third stage of the study, the researchers used a different method to perform genotyping from the method used in stages 1 and 2 to look at the difference between 91 never smoker lung cancer patients and 439 controls at UCLA. "We confirmed the variant-lung cancer association again," Dr. Yang says.

The final stage of the study involved understanding the function of the gene. "We had to understand whether these hits really represented the functional aspect of the gene, so we tested expression level of GPC5 and found it was significantly reduced," Dr. Yang says. They found that the GPC5 transcription level was twofold lower in adenocarcinoma compared to normal lung tissue. "Interestingly, this reduced transcript expression level was not found in lung carcinoid tumors," Dr. Yang says.

Then the researchers looked to see if this reduced expression led to tumor development, which it did in laboratory culture. "If reduction of expression of this gene leads to development of lung cancer, it suggests that this gene is normally a tumor suppressor," Dr. Yang says. "We believe it helps control the cell proliferation and division, but we need to prove its function in animal models."

They calculated that about one-third of never smoker lung cancer patients in this study had the same variation of the underperforming GPC5 gene. "We hypothesize that this is an important cancer trigger in these patients, and that something else is going on in the remaining two-thirds of never smokers," she says.

"We don't know what that is, but we now have 42 ot
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Contact: Karl Oestreich
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Source:Eurekalert

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