Lung cancer remains the leading cause of cancer-related deaths. Although smoking is largely attributed to the prevalence of lung cancer, a significant portion of lung cancer patients have never smoked. As researchers continue to evaluate potential associations for the risk of developing lung cancer among never-smokers there is increasing evidence of a genetic component of developing lung and other cancers. Specific genes increase the risk of developing breast, ovary, and other cancers, but evidence is just beginning to emerge for a genetic susceptibility in lung cancer.1-4
Results from a study released at the 2022 ASCO annual meeting revealed that nearly 15% of patients with lung cancer have pathogenic germline variants (PGVs), putting them and their family members at an increased risk for other types of cancers.4
These genetic changes are inherited and are present from the time of conception. PGV’s differ from acquired genetic changes (somatic mutations), which occur throughout a person’s life. Somatic genetic changes are often caused by factors, such as tobacco use and aging, and are the most common cause of cancer.
The new data comes from a study where germline DNA sequencing was conducted on 7,788 patients with lung cancer. The study found that 15% of patients had PGVs in 81 known cancer-risk genes most of which can be managed with currently available strategies. Over half of patients had a PGV in the DNA damage-repair (DDR)/homologous recombination-repair (HRR) genes associated with hereditary cancer syndromes.
Research suggests that individuals with a first-degree relative who has been diagnosed with lung cancer are at a two-fold increased risk of developing lung cancer, regardless of smoking status.
Researchers from Japan conducted a clinical study to evaluate the risk of developing lung cancer among individuals with a first-degree relative who had been diagnosed with lung cancer. This study included 102,255 participants who were middle-age or older. Follow-up was 13 years.1
- Among individuals with a first-degree relative with lung cancer, the risk of developing lung cancer was nearly double.
- The risk was greater in women than in men with a first-degree relative; however, men were still at a significantly higher risk of developing lung cancer.
- The risk was particularly increased for a type of non–small cell lung cancer referred to as squamous cell lung cancer.
The researchers concluded that individuals with a first-degree relative who has been diagnosed with lung cancer have approximately double the risk of developing lung cancer. Further studies will help explain these findings; however, patients should discuss their family history of lung cancer with their physician.
Family History of Early-Onset Lung Cancer Increases Risk of Lung Cancer
First-degree relatives of patients with early-onset lung cancer also have an increased risk of smoking-induced lung cancer. This risk is greater in black individuals than in white individuals.
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A clinical study conducted by researchers from Karmanos Cancer Institute sought to identify persons at a high risk for developing smoking-related lung cancer. The researchers evaluated data from 7576 first-degree relatives of 692 individuals diagnosed with lung cancer before 50 years of age (early-onset lung cancer). Overall, among white individuals, first-degree relatives of early onset lung cancer patients had a 17.1 percent chance of developing smoking-induced lung cancer by the time they were seventy years of age. Among black individuals, that rate was increased to 25.1 percent.2
The researchers concluded that individuals who smoke and have a first-degree relative diagnosed with early-onset lung cancer have an increased risk of developing the disease. Furthermore, data revealed that black individuals’ risk of developing smoking-induced lung cancer is higher than their white counterparts. Patients who are smokers and have a first-degree relative diagnosed with early-onset lung cancer should speak with their physician about screening for lung cancer.
Further Data Indicates Hereditary Link to Lung Cancer
Individuals who have family members diagnosed with lung cancer, particularly those whose family members were diagnosed at an early age, are at a significantly increased risk of developing lung cancer themselves.
Researchers from London conducted a clinical study to evaluate potential familial associations for lung cancer. This study included 579 individuals who had been diagnosed with lung cancer and 1,157 individuals who did not have lung cancer (controls). Questionnaires regarding family history of lung cancer were obtained from these participants.
- Participants under 60 years of age had a five-fold increased rate of lung cancer if they had first-degree relatives who had been diagnosed with lung cancer at the age of 60 years or younger.
- Participants of any age had an approximate two-fold increased rate of lung cancer if they had a first-degree relative who had been diagnosed with lung cancer at the age of 60 years or younger.
- The risk of developing lung cancer for a participant was increased as the number of relatives who had been diagnosed with lung cancer increased.
The researchers concluded that individuals who have a family member who was diagnosed with lung cancer under the age of 60 years have a greater risk of developing lung cancer themselves. These results lend to a growing body of evidence indicating that a family history of lung cancer appears to be linked with a higher risk of developing lung cancer.
Individuals should discuss their family history of lung and other cancers with their physician, as well as their individual risks and benefits of screening for lung cancer. The importance of taking a family history can help determine if germline testing is needed.
- Natadori, J, et al. Association Between Lung Cancer Incidnece and Family History of Lung Cancer: Data From a Large-Scale Population-Based Cohort Study, the JPHC Study. Chest. 2006; 130:968-975.
- Cote ML, Kardia SLR, Wenzlaff AS.Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer. Journal of the American Medical Association. 2005;293:3036-3043.
- Cassidy A, Myles J, Duffy S, et al. Family History and Risk of Lung Cancer: Age-At-Diagnosis in Cases and First-Degree Relatives. British Journal of Cancer. 2006:95;1288-1290.