Lung cancer in smokers versus non-smokers shows different genetic mutations

By Dr. Ananya Mandal, MDNov 10 2010

Genetic connection

A group of scientists at B.C. Cancer Agency have found that lung cancers in smokers have different genetic mutations and look different than lung cancer in non-smokers. According to senior scientist at the BC Cancer Agency Research Centre Wan Lam, this finding is significant because it means that from now on, research, treatments and diagnostics should be tailored to the distinct genetic variations in the different lung cancers instead of expecting that a one-size fits all approach will work. He said, “At the current time, treatment does not distinguish between these different types. The subtypes are all grouped together. But with this work, we are beginning to tease out the subtypes.” The study was presented Tuesday at a conference in Philadelphia of the American Association of Cancer Research.

It is found that lung cancer tumors in patients who had never smoked actually had twice as many genetic abnormalities (DNA mutations) as those who were current or former smokers. For the study the team compared tissue samples of 30 individuals who had never smoked and 53 who were either current smokers or former smokers. This study is the first to find out whole regions of mutations.

Epidemiological studies show that up to 15 per cent of lung cancer cases are non and never smokers. For some unknown reason, never smokers who get lung cancer are more likely to be female. Study co-author Kelsie Thu explained that cancer-causing substances in cigarettes trigger DNA mutations that lead to cancer cell growth, in non-smokers, but it is now apparent there are other mechanisms causing tumor development. Study co-author Raj Chari also said that it is a challenge to detect lung cancer among non-smokers early since they tend to be diagnosed in the advanced, incurable stages because no one suspects they could possibly have lung cancer.

Thu explained that people who never smoked are also more likely to have a mutation in the epidermal growth factor receptor (EGFR) gene. “All of those differences are evidence there may be something different going on with their tumors.” Thu said. Never-smokers with lung cancer were also less likely to have the KRAS mutation, which has also been shown in prior research.

Early diagnosis

Last week the National Cancer Institute also released a study showing that deaths from lung cancer were 20 per cent lower in people who got a CT scan compared to those who got a chest X-ray, an important finding since CT scans are not currently part of routine, lung cancer screening guidelines. November 4^th this year also saw the announcement of the National Lung Screening Trial results that showed that CT screening was shown to save lives in its 53,000 person study brings wide hope that deaths from the country's leading cancer killer can be significantly reduced.

In another Canadian study presented in Philadelphia Dr. Stephen Lam, a lung cancer expert at the BC Cancer Agency and co-author say there has been only a three-per-cent reduction in lung cancer mortality using current management strategies [so] “we welcome a screening modality that can potentially reduce lung cancer deaths by 20 per cent.” Dr Lam added, “In Canada, a study is well underway to investigate the most effective ways of screening people at high risk for lung cancer. Co-funded by the Terry Fox Research Institute and the Canadian Partnership Against Cancer, the Early Lung Cancer Detection Study began two years ago and is taking place ... across the country…the Canadian study is evaluating the effectiveness of identifying high-risk individuals using a breathing test, questionnaires and a blood biomarker test. By exploring ...these lower-cost tests to triage high-risk individuals, we will have scientific evidence to help us determine how to proceed," he added, referring to the study which should be completed next year.”

Gene based diagnosis

In studies that included 1,216 lung cancer cases and 1,200 controls gathered from smokers and ex-smokers in three countries, the Respiragene test accurately identified a subgroup of very high risk smokers (20 percent of the at-risk population) who accounted for just over 50 percent of all lung cancer cases.

Dr. Robert Young, Associate Professor of Medicine and Molecular Genetics at the University of Auckland, who presented the genetic test study results said, “The medical challenge to understand who is most likely to develop lung cancer has become even more urgent with the recent evidence that a regular screening program with CT scans of smokers can save lives…Now that the broad benefit of screening for lung cancer has been confirmed, there’s a pressing need to better target screening resources on those individuals who are most at risk from this disease.”

The Respiragene test was developed by researchers at the University of Auckland led by Dr. Robert Young, based on the then novel view that the genetic factors underlying lung cancer predisposition overlap with the genes underlying susceptibility to COPD (Chronic Obstructive Lung Disease).