Genetic variants, tobacco exposure and lung cancer risk

April 25, 2012

There is an association between the rs1051730-rs16969968 genotype and objective measures of tobacco exposure, which indicates that lung cancer risk is largely, if not entirely, mediated by level of tobacco exposure, according to a study published April 25 in the Journal of the National Cancer Institute.

The rs1051730-rs16969968 genotype is known to be associated with heaviness of smoking, lung cancer risk, and other smoking-related outcomes. Prior studies have generally depended on self-reported smoking behavior, which may have underestimated associations and masked the contribution of heaviness of smoking to the associations of these with lung cancer and other .

In order to determine the association between the rs1051730-rs16969968 genotype and self-reported cigarette consumption and plasma or serum cotinine levels, Marcus R. Munafò, Ph.D., of the School of Experimental Psychology at the University of Bristol and colleagues, examined data from six independent studies that looked at self-reported daily cigarette consumption and plasma or serum cotinine levels among cigarette smokers and conducted a meta-analysis of pooled per-allele effects. In addition, the researchers looked at the link between the genotypes and lung cancer risk using published data on the association between cotinine levels and lung cancer risk.

The researchers found that the rs1051730-rs16969968 genotype is strongly associated with tobacco exposure measured through cotinine levels, and that the association is strong even after adjustment for self-reported cigarette consumption. "These data therefore support the conclusion that association of rs1051730-rs16969968 with lung cancer risk is mediated largely, if not wholly, via ," the researchers write.

The researchers point out certain limitations of the study, however, namely that the data were drawn from disparate studies from various populations. The data also relies on current smoking measures, rather than lifetime exposure, which is more strongly associated with lung .

However, they have confidence in their results, which show that phenotype precision is important to uphold in GWAS studies, rather than ever-larger sample sizes, they say. "The use of objective measures of smoking behavior in genome-wide studies may reveal novel variants associated with these outcomes, which would be undetectable using conventional self-report measures."

In an accompanying editorial, Margaret R. Spitz, M.D., MPH, of the Department of Molecular and Cellular Biology at the Dan L. Duncan Cancer Center at Baylor College of Medicine, writes that these findings "confirm that cigarettes per day is an imprecise measure of nicotine consumption, and favor the interpretation that the association between these variants and lung cancer is mediated by smoking. But the degree to which the association is mediated by is yet to be determined." They add that more studies, including mouse and cellular models, along with emerging metabolic markers, "may help tease apart the direct and indirect associations of these variants with risk."

Explore further: Latest research confirms genetic susceptibility to lung cancer

Related Stories

Latest research confirms genetic susceptibility to lung cancer

April 15, 2012
Previous research has shown that Asian patients with lung cancer are more likely to harbor epidermal growth factor receptor (EGFR) mutations. Furthermore, Asian patients with lung cancer are more likely to be non-smokers ...

Early morning smokers have increased risk of lung and head and neck cancers

August 8, 2011
Two new studies have found that smokers who tend to take their first cigarette soon after they wake up in the morning may have a higher risk of developing lung and head and neck cancers than smokers who refrain from lighting ...

Smoking soon after waking raises risk of lung and head and neck cancers

August 25, 2011
Two new studies have found that smokers who tend to take their first cigarette soon after they wake up in the morning may have a higher risk of developing lung and head and neck cancers than smokers who refrain from lighting ...

Heavy alcohol consumption linked to lung cancer

October 24, 2011
Heavy alcohol consumption may be linked to a greater risk of developing lung cancer, while higher BMI and increased consumption of black tea and fruit are associated with lower risk of the deadly disease. In three separate ...

Recommended for you

Comparison of screening recommendations indicates annual mammography

August 21, 2017
When to initiate screening for breast cancer, how often to screen, and how long to screen are questions that continue to spark emotional debates. A new study compares the number of deaths that might be prevented as a result ...

Vitamin C may encourage blood cancer stem cells to die

August 17, 2017
Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone ...

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.