'Smoking' gene linked to cancer

2008-04-03 12:12

Paris - Three independent studies released on Wednesday have identified a tiny variation in the human genome that make some people more vulnerable to lung cancer than others.

While they all finger the same culprit, however, the studies disagree on whether the genetic glitch - shared by 50% of the population - increases the risk of cancer by itself, or only in people who smoke.

They also differed on whether, the rogue gene simply enhanced the addictive quality of tobacco among smokers or provoked cancer-causing chemical reactions in the lungs.

Lung cancer is the most common cause of cancer death worldwide, with more than one million new cases every year.

Taken together the studies, published in the British journal Nature, "give us new targets for both the prevention and the treatment of lung cancer", said Nora Volkow, director of Britain's National Institute on Drug Abuse.

The three papers also highlight the growing importance of new tools that allow researchers to sift through huge swathes of the human genome in search of tiny variants linked to specific diseases.

The basic technique, made possible only recently by improvements in computing power, is to compare the genetic profiles of thousands - or tens of thousands - of people with a specific disease against the profile of healthy people, looking for tell-tale differences.

A 50-50 chance

A team jointly led by Richard Houlston of Britain's Institute of Cancer Research and Christopher Amos at the University of Texas found that an extra copy of two critical genetic variants increased the chances that current or former smokers would contract lung cancer by 38%.

With two extra copies, the added risk among the subjects studied - some 3 800 smokers of European descent in Texas and Britain, half of them cancer patients - jumped to 80%.

The cancer-causing genetic snippets are on chromosome 15, involving a molecular swap in just one of the three billion chemical "base pairs" that comprise the building blocks of the human genome.

"We've found that these genetic variants are strongly associated with lung cancer," said Houlston.

Both smokers and non-smokers have a 50-50 chance of carrying them, he noted, but "they only increase the risk of lung cancer in people who have smoked".

The study further concluded that the wayward gene - known as rs1051730 - promoted cancer not by driving people to smoke more, but by interacting directly with tobacco.

A second study, led by Kari Stefansson of deCODE Genetics in Iceland, incriminated the same bit of genetic code, called a single nucleotide polymorphism (SNP), but reached the opposite conclusion on how it works.

Genetic test

The genetic analysis of 10 000 smokers in Iceland showed that the offending SNP was more common in heavy smokers that among light smokers or non-smokers, leading the researchers to conclude that it boosted nicotine dependence.

Earlier studies have shown that the same part of the chromosome that lodges rs1051730 also encodes nicotine receptors expressed in lung and lung-cancer cells.

deCODE, a private company, is planning to market a genetic test that would allow individuals to find out if they had the gene variant favouring lung cancer.

The third study, led by Paul Brennan of the International Agency for Research on Cancer in Lyon, France, supported the other two in drawing a strong link between the disease and rs1051730, saying the genetic variant accounted for 14% of all lung cancer cases.

But it differed from the others in finding a statistically similar risk of contracting the disease regardless of whether one smokes or not.

In a comment, also published in Nature, epidemiologists Stephen Chanock of the US National Cancer Institute and David Hunter of Harvard University caution that the divergence interpretations shows that further, large-scale studies are needed.

"These are the first genome-wide association studies to attempt to identify the genetic component of a disease that has such an overwhelmingly strong environmental cause," they write.

"They signal the need for greater methodological rigour."

- AFP