Genetic Background Determines Lung Cancer Risk in Smokers

Lung cancer is common among smokers worldwide, but not everyone faces the same level of risk. New research from the University of Navarra Clinical Cancer Center reveals how genetic profiles affect smokers' lung cancer risk. It may help us understand the role of genetic factors in risk assessment, early diagnosis and treatment strategies. Here are the details:

The Basis of the Research: Smoking, Lung Cancer and Genetic Factors

A multidisciplinary study by the University of Navarra Clinical Cancer Center (CUN) found that smokers with high and low lung cancer risk have different genetic profiles. The results were presented at the latest American Society of Clinical Oncology meeting in Chicago (ASCO 2023).

Dr. Ana Patiño García, director of CUN's Genomic Medicine Unit and the study coordinator, explained why the research was undertaken: "This study emerged directly from the oncology clinic, where we continually see lung cancer patients who have never smoked or have smoked very little. We also know many people who smoked for much of their lives without developing cancer. This observation led us to ask whether genetic factors increase or decrease cancer risk and protect people against the disease", she said.

Dr. José Luis Pérez Gracia, coordinator of CUN's Oncology Trials Department and the researcher responsible for the study, said: "This study confirms for the first time the genetic factors associated with people who appear resistant to tobacco-related lung cancer or who are at high risk of developing it."

An Innovative Approach: Next-Generation Techniques and Artificial Intelligence

Previous findings show that some smokers develop cancer while others do not. Pérez explains: "It is widely recognized that some older people have smoked heavily yet have not developed lung cancer. Unfortunately, we oncologists also frequently encounter smokers diagnosed at a young age. Although understanding the reasons behind these phenomena is very important, the issue has never previously been investigated genetically."

The study used samples from:

• 133 heavy smokers with an average age of 80 who had not developed lung cancer, and
• 116 heavy smokers with an average age of 50 who had developed lung cancer, providing DNA samples for the research.

This DNA was analyzed using next-generation sequencing (NGS) techniques. Results were analyzed using bioinformatics and artificial intelligence systems in collaboration with the University of Navarra's Center for Applied Medical Research and its School of Engineering.

Asked how this methodology might support other research along these lines, Patiño said: "The most novel aspect is the approach itself. It uses groups at the extremes, defined by age at lung cancer onset and smoking exposure. This comparative design is called extreme phenotypes, and its main distinguishing feature, also its greatest limitation, is selecting cases and controls carefully. Clearly, today's NGS technologies provide a quantity and quality of data that would have been unattainable years ago".

Discussing the role of bioinformatics and artificial intelligence, Patiño explained that these are very new techniques: "These technologies have actually become part of the strategies used today to understand, identify and even treat cancer. This approach is used clinically to understand differences between individuals, predict treatment response and make treatment decisions," she said.

Identifying Genetic Differences

The research revealed how different genetic factors affect lung cancer risk. The presence of certain genes may increase or decrease risk among smokers. These findings could help develop earlier diagnosis or even personalized treatment strategies.

According to the findings:

• Both groups showed genetic differences.
• These differences were found in:
  • the immune system -related genes (the HLA system),
  • genes related to functional pathways frequently altered during tumor development, and
  • genes involved in cell movement.
• The genetic features identified are located in genes with cancer-related functions, such as the immune response, repair of genetic material and regulation of inflammation.

Earlier Diagnosis: Findings and Clinical Application

This study could be an important step in lung cancer diagnosis and treatment. Understanding genetic profiles may give doctors the information needed to provide earlier and more effective treatment.

Next Steps: Current Problems and New Techniques

This research may inform future studies. Better understanding and treatment of patients at risk of lung cancer require moving beyond current technologies and methods. Understanding genetic differences could open new avenues for more effective treatment and even prevention.

Conclusion

This research reveals how smokers' genetic profiles affect lung cancer risk. The findings may help patients receive earlier diagnosis and treatment, guide future research and improve understanding, care and even prevention. This could be an important step in the fight against lung cancer.

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Further Reading: Genetic Differences Identified and Their Effects on Cancer Risk

Case Group (average age 50, heavy smokers with lung cancer):

• HLA-A: With 4 variants (genetic changes), it has an antigen-presentation function. This gene plays an important role in the immune response.
• ADAMTS7: With 2 variants, it has a metalloproteinase function. This gene plays a role in regulating tissue and cell structure.
• SPINK5: With 2 variants, it has a tumor-suppressor function. This gene may help prevent cancer cells from growing and spreading.
• REXO4: With 2 variants, it has a DNA-repair function, helping repair DNA when it is damaged.

Control Group (average age 80, heavy smokers without lung cancer)

• PLIN4: With 2 variants, it has a lipid-droplet metabolism function. This gene plays a role in energy storage and metabolism.
• ZNF214: With 2 variants, it has a transcriptional regulation function. This gene helps regulate gene expression.
• KRT18: With 1 variant, it has a Ras-activated oncogene function. This gene is involved in cancer development and progression.

These variants reflect genetic differences between the disease and control groups and may affect cancer risk and resistance. In particular, the prominence of genes such as HLA-A and ADAMTS7 in people with lung cancer and PLIN4 in controls suggests that these genes may influence different cancer-related pathways.

These specific variants and genes may improve understanding of risk factors for certain cancers and could help develop more effective treatment and prevention strategies in the future.