Study demonstrates the importance of familial factors in the general development of cancer

Studying thousands of people, researchers at The University of Texas M. D. Anderson Cancer Center have documented a 25 percent increased risk of developing one of a number of cancers in first-degree relatives of lung cancer patients who have never smoked compared to families of people who neither smoke nor have lung cancer.

Researchers say their study, one of the largest ever done and the only one to include both men and women, strongly suggests that these lung cancer patients and their affected relatives share an inherited genetic susceptibility to cancer development.

"This study demonstrates the importance of familial factors in the general development of cancer," says the study's first author, Olga Gorlova, Ph.D., assistant professor in the Department of Epidemiology. "These susceptibility factors can be environmental, but are more likely to be influenced by genetic factors, because genes control pathways common to a number of cancers."

Such marked cancer susceptibility also likely explains why patients in this study, who never smoked but might have been exposed to secondhand smoke, developed lung cancer in the first place, she says. Gorlova will present the study at the annual meeting of the American Association for Cancer Research (AACR). She will discuss the findings in a press briefing on Tuesday, April 4, 2006 at 11 a.m.

The research team, headed by Margaret Spitz, M.D., professor and chair of the Department of Epidemiology, looked at whether 2,465 first-degree relatives of 316 lung cancer patients who never smoked developed cancer. They also established a matched comparison group of 2,442 first-degree relatives of 318 "controls" - individuals who also never smoked but did not have lung cancer. (An individual's first-degree relatives include his/her parents, children and siblings - people who share one-half of that individual's genes.)

The median age of both cases (patients) and controls was about 61 years, and the median number of first-degree relatives was eight for both groups.

The researchers compared cancer incidence between the two groups adjusting their findings to eliminate the influence of age, gender, ethnicity and smoking status.

They discovered:

• First-degree relatives of cases had a 25 percent increased risk of developing any type of cancer, compared to controls. Cancers diagnosed in the relatives include melanoma, colorectal, head and neck cancer, lung, prostate and breast cancers.
• Case relatives were about 10 years younger when they were diagnosed with cancer, compared to control relatives.
• A 44 percent excess risk of young onset cancers - those diagnosed before age 50 - among case relatives.
• More than a six-fold risk of developing young onset lung cancer in the case families compared to control families.
• Relatives of case patients had a 68 percent increased risk of developing lung cancer.
• Mothers of case patients had more than a two-fold risk of developing breast cancer.

"It has long been observed that cancer seems to occur in some families more than in others, and with the help of this unique group of lung cancer patients and their relatives, we can begin to understand why that might be the case," says Spitz.

The research team plans next to compare specific genes, such as those that help repair DNA damage, between the groups.