Gene variants behind cigarette smoke metabolism linked to lung cancer risk

December 23rd, 2008 - 6:14 pm ICT by ANI  

Washington, Dec 23 (ANI): People who have particular variants of certain genes, involved in metabolising the most potent carcinogen found in cigarette smoke, are more likely to develop lung cancer, according to a new study.

Led by Dr. Daru Lu and Dr. Haijian Wang of the Fudan University in Shanghai, the study may offer new insights on how lung cancer develops, and could have important implications for preventing smoking-related cancers.

Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a component of cigarette smoke that has been shown to cause lung cancer in rodents.

Certain enzymes act to protect the body from this type of chemical by turning it into nontoxic forms or by transporting it from cells. For instance, ATP-binding cassette transporters encoded by genes known as ABCB1 and ABCC1 are involved in eliminating carcinogens from the lungs, protecting them against inhaled toxins.

Scientist hypothesised that individuals with alterations in these genes might have an increased susceptibility to develop lung cancer.

And in the recent study the researchers identified common variants at the beginning and end of the ABC1 and ABCC1 genes. Later, they analysed these variants in 500 patients with lung cancer and 517 cancer-free controls in a Chinese population.

It was observed that certain variants were seen much more often in individuals with lung cancer than in cancer-free controls.

Patients who had the variant allele of either ABCB1 rs3842 or ABCC1 rs212090 had a significantly increased risk of developing lung cancer, with the former variant particularly associated with an increased risk of cancer in women and in individuals under age 60 years.

It was also linked to a major type of lung cancer called adenocarcinoma.

In an earlier study, the researchers identified other common genetic variants associated with lung cancer risk in NNK disposition pathways, such as CYP2A13, the most active P450 for the phase metabolic activation of NNK and the receptor (ADRB2) in its non-genotoxic pathway.

The current study shed new insight into the toxicogenomics of NNK and further supported the hypothesis proclaiming genetic components in the metabolism and disposition machines of NNK as modifiers of risk of lung cancer.

“Because tobacco smoking is the leading preventable cause of cancer and the cancer-prone genotypes of these genetic components are relatively prevalent in the human population, our findings have important implications for the prevention of tobacco smokingrelated cancers,” wrote the authors.

The study has been published in the latest issue of CANCER, a peer-reviewed journal of the American Cancer Society. (ANI)

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