Key Points

First-degree relatives of individuals with lung cancer have an increased risk of any cancer. A new risk assessment model identifies history of emphysema, smoking, and suboptimal DNA repair as risk factors for lung cancer.

WASHINGTON, DC—Findings from two studies may help clinicians predict lung cancer risk as well as variables that might protect against lung cancer. At the 97th Annual Meeting of the American Association for Cancer Research, researchers from the University of Texas M. D. Anderson Cancer Center reported that first-degree relatives of never-smoking lung cancer patients have a 25% increased risk of developing one of a number of cancers.¹ Furthermore, using a prototype risk assessment model, they detected an approximate 11-fold increased risk of lung cancer in heavy smokers ( greater than or equal to 40 pack-years) with emphysema who possess inefficient DNA repair capacity.²

LUNG CANCER RUNS IN FAMILIES

"This study demonstrates the importance of evaluating the familial aggregation of cancer," said Olga Gorlova, PhD, Assistant Professor in the Department of Epidemiology. "It implies that these susceptibility factors can include genes involved in pathways common to a number of cancers."

The authors evaluated the cancer history of 2,465 first-degree relatives of 316 never-smoking patients with lung cancer and 2,442 first-degree relatives of 318 controls who were matched for age, gender, ethnicity, and smoking status. The median age of lung cancer patients and controls was 61; two thirds were women, and 80% were Caucasian. The median number of relatives both per lung cancer case and per control subject was eight, and the mean age of first-degree relatives was 53.7 for case relatives and 53.5 for control relatives. The researchers compared self-reported cancer incidence between both groups of relatives, adjusting their findings to eliminate the influence of age, gender, ethnicity, and smoking status.

Dr. Gorlova and colleagues found that first-degree relatives of lung cancer patients had a 25% increased risk of any type of cancer and a 44% increased risk of young-onset cancers (diagnosed before age 50)—particularly lung cancer—compared with first-degree relatives of controls. Children of lung cancer patients had a twofold increased risk of any cancer. Compared with smoking relatives of controls, smoking relatives of lung cancer patients had an increased risk of lung cancer. In addition, mothers of lung cancer patients had a 2.22-fold increased risk of breast cancer. The researchers also observed an elevated risk of testicular cancer among male relatives of lung cancer patients.

"These data demonstrate the importance of familial (probably genetic) factors in lung cancer etiology in never smokers and provide estimates that may be helpful in counseling family members of never smoking lung cancer patients," concluded the researchers.

A NEW RISK ASSESSMENT MODEL

In a separate data analysis from the same ongoing study, the researchers are developing a risk assessment model for the early detection of lung cancer. "Our goal is to develop an instrument that can help physicians estimate the risk for developing lung cancer, like the Gail model does for breast cancer, or the Framingham model used to predict heart disease," said Matthew Schabath, PhD, a postdoctoral researcher in the Department of Epidemiology.

Dr. Schabath and his colleagues compared self-reported histories of emphysema and exposure to cigarette smoke and/or asbestos in 2,134 lung cancer patients and 2,295 matched healthy controls and incorporated available data on DNA repair capacity. DNA repair capacity was determined by measuring how efficiently participants’ lymphocytes—drawn into a test tube—repair damage incurred by a tobacco carcinogen.

Overall, the researchers found that suboptimal DNA repair capacity was associated with a 1.4-fold increased risk of lung cancer, and a history of emphysema was associated with a 2.6-fold increased risk. Heavy smokers with a history of emphysema exhibited nearly a fourfold increased risk of lung cancer compared with light smokers without emphysema. The risk of lung cancer increased to nearly 11-fold if a heavy smoker with a history of emphysema also had inefficient DNA repair capacity.

Clinical variables that appear to protect against lung cancer are also being incorporated into the model, said Dr. Schabath. Individuals with a history of allergies (ie, a history of hay fever) had a 29% reduced risk of lung cancer. Furthermore, such individuals, who also exhibit efficient DNA repair capacity, have a 56% reduced risk of lung cancer, compared with those who have neither allergies nor efficient DNA repair capacity.

They concluded that "assessing multiple risk factors including relevant susceptibility markers, history of respiratory conditions, and deleterious exposures may reveal a more accurate representation of lung cancer risk and help in the identification of subgroups that are at the greatest risk for developing lung cancer."

—Karen L. Spittler

Reference
1. Gorlova O, Zhang Y, Amos C, et al. Aggregation of cancer among relatives of never smoking lung cancer patients. Presented at: annual meeting of the American Association for Cancer Research; April 2, 2006; Washington, DC.
2. Schabath MB, Wei Q, Wu X, Spitz MR. Prior respiratory disease, DNA repair capacity, and inflammation-related genotypes modify lung cancer risk. Presented at: annual meeting of the American Association for Cancer Research; April 5, 2006; Washington, DC.

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