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AACR: Relatives of Never-Smoker Lung Cancer Patients at Risk

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http://www.medpagetoday.com/2005Meeting ... ng/tb/2975

By Rabiya Tuma, Ph.D., MedPage Today Staff Writer

Reviewed by Robert Jasmer, MD; Assistant Professor of Medicine, University of California, San Francisco

April 03, 2006

MedPage Today Action Points

Be aware that never-smoker lung cancer patients may have a genetic predisposition to cancers. Their family members are also at increased risk of malignancies.

Advise patients who have a first-degree relative who was a never smoker and had lung cancer of the risk to themselves.

This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.


WASHINGTON, April 3 - First-degree relatives of lung cancer patients who are never-smokers have a 25% increased risk of developing any malignancy, investigators reported here in a case-control study.

The excess risk included breast cancer (95% CI [1.16-4.24]) and testicular cancer (OR=8.92, 95% CI [1.10-72.43]), Olga Gorlova, Ph.D., and colleagues at the University of Texas M.D. Anderson Cancer Center in Houston reported at the American Association for Cancer Research meeting here.

What's more, for the relatives who are smokers, the excess risk climbed to 36% compared with smoking relatives of controls.

The report emerged within weeks of the lung-cancer death of singer Dana Reeve, a non-smoker. About 13% of lung cancer patients are non-smokers.

Never-smoker lung cancer patients likely represent a genetically susceptible subgroup of cancer patients, the Texas investigators said. Researchers at Memorial Sloan-Kettering Cancer Center in New York reported last year that a mutation in the gene for epidermal growth factor is more common in non-smokers with lung cancer than in smokers.

The M.D. Anderson group evaluated the rate of malignancies in 2,465 first degree relatives of never-smoker lung cancer patients and in 2,442 first-degree relatives of 318 matched controls. The overall increase was 25% (95% CI [1.05-1.50]).

In addition to the overall excess cancer risk detected in the never-smoker relatives, the scientists found that the group had a 44% excess risk (95% CI [1.05-1.97]) for young-onset cancers, which were defined as those malignancies diagnosed prior to the age of 50.

The excess risk was exaggerated in men, with 36% overall increase in any malignancy and an 89% increase in young onset cancers, relative to control family members.

Furthermore, the offspring of the never-smoker cases had a two-fold increased risk of cancer ([95% CI [0.99-4.10]).

Lung cancers risks were also significantly elevated in the family members of never-smokers relative to the control family members. Overall the was a sixfold increase in the likelihood of young onset of lung cancer in the case families, and males had a two-fold risk of lung cancer relative to controls. Family members who smoked had a 68% increase in the likelihood of lung cancer, making them a priority target for cessation and screening programs, the researchers said.

There was a non-significant trend for early lung cancer diagnoses in the family members of never-smokers than in the control families, with a median age at diagnosis of 61.4 versus 66.2 (p=.07). The trend remained for non-smoking family members, with an average of 13 years earlier onset, and a median age of diagnosis of 60.6 versus 74.2 (p=0.055). The trend for earlier diagnosis was also apparent in the mothers of cases, with a median age at lung cancer diagnosis of 51.9 versus 74.1 (p=0.001).

The parents of controls were more likely to have smoked than the parents of cases, and thus the researchers ruled out exposure to parental smoking as a cause of disease in the never-smoker cases. Lung cancer occurred earlier in smokers in the control families, than in non-smokers, 63.5 versus 74.2 (P=.008). No such age difference was detected between the smokers and non-smokers in the case families, with a median age of diagnosis of 61.5 versus 60.5.

Finally, Dr. Gorlova and colleagues found an excess of other specific cancers in the family of cases, including a 58% increase in risk of breast cancer in female relatives, and a 12-fold excess of testicular cancer in male relatives. Additionally, mothers of cases had a 2.2 fold excess risk of breast cancer.

The researchers are now looking for the genetic factors that likely underlie these increased risks. In the meantime, however, they stressed that family members of cases should be counseled to stop smoking. "Relatives could be aggressively advised to stop smoking or, if lung cancer screening is recommended at some point in the future, this is a high-risk group that could be considered for regular screening," said Dr. Gorlova.

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