Defect in Alpha-1 Antitrypsin Gene Found to Increase Colorectal Cancer Risk

Wednesday, January 03, 2001

ROCHESTER MINN. — Mayo Clinic scientists have discovered that carriers of a genetic defect previously linked to emphysema have a threefold increased risk of developing a type of sporadic colorectal cancer. Carriers who currently smoke have a 20-fold increased risk.

"This study provides important new insight into the controversy surrounding the link between cigarette smoking and colorectal cancer, confirming a strong association in a subgroup of colorectal cancers," says Dr. Ping Yang, Mayo Clinic clinical epidemiologist and principal investigator of the study.

The genetic defect, alpha-1 antitrypsin deficiency, presents an inadequate level of the protease inhibitor alpha-1 antitrypsin, which protects the surfaces of multiple organs. Alpha-1 antitrypsin is synthesized primarily in the liver and in a small amount of the gastrourinary systems. In individuals who lack this inhibitor, the protease destroys the membrane system, leaving the colon and rectum vulnerable to colorectal cancer development.

The investigators believe that cigarette smoking causes a similar effect, further exacerbating tissue destruction for carriers of alpha-1 antitrypsin deficiency, since smoking is a strong inactivator of the protease inhibitor alpha-1 antitrypsin.

In this study, published in Molecular Genetics and Metabolism, 161 Mayo Clinic patients newly diagnosed with colorectal cancer were compared to 191 controls. The relative risk of developing colorectal cancer demonstrating microsatellite instability, a nonhereditary type of colorectal cancer, was 3.1 for alpha-1 antitrypsin deficiency carriers; among current and past smokers who were not carriers, the risk of developing this type of colorectal cancer was 6.6 and 2.7, respectively. The risk for those who were both alpha-1 antitrypsin deficiency carriers and current smokers, relative to never smokers who lacked the genetic defect, was elevated 20 times.

Since alpha-1 antitrypsin deficiency previously has been associated with emphysema, the investigators suggest those with severe, early-onset emphysema in their families inquire of their physicians regarding their potential carrier status for alpha-1 antitrypsin deficiency. Phenotyping (a protein test) is currently available to detect alpha-1 antitrypsin deficiency carrier status.

Mayo Clinic scientists, under the leadership of Dr. Stephen Thibodeau, molecular biologist, and Dr. Jerry Katzmann, immunopathologist, are investigating new, potentially more efficient genotyping, or DNA testing, methods.

The study investigators indicate there is one step people can take that will definitely reduce their risk of colon cancer. "One thing people can do for sure is not smoking," says Dr. Yang., "Smokers should be aware that they are not only at risk for lung cancer and heart diseases, but colorectal cancer as well." Source: Molecular Genetics and Metabolism, Volume 71, Number 4, December 2000.

Physicians Can Do More to Ensure Quality of Life for Terminally Ill Patients.

ROCHESTER, MINN. — Physicians can do more and involve additional people in the care of the terminally ill patients to ensure that their quality of life doesn't deteriorate in their final days.

The Mayo Clinic authors note that physicians as a group may prolong the end-of-life suffering with aggressive approaches to "cure" the patients' underlying disease rather than acknowledging that the time has come to provide the patient with palliative care services. However, strategies can be taken to reduce the suffering of a patient by orchestrating a multidimensional approach to helping ensure the quality of life at the end.

The special article, done for the Mayo Clinic Cancer Center Quality of Life Working Group, appears in Mayo Clinic Proceedings.

Before the 1900s, most Americans died at home surrounded by their loved ones. Currently, as many as 60 percent will die in hospitals, and up to an additional 25 percent will die in healthcare-related facilities such as nursing homes. The role of the physician has had an ever-expanding role in the manner which people die with so many Americans dying in hospitals and other health care facilities.

"With modern medicine emphasizing genetic manipulations, high technology, and cure at all costs, we often neglect what was once the most sacred aspect of being a physician: alleviating suffering," the authors write. "Therefore, we contend that the approach to a person dying in the hospital must change from simply postponing death to focusing medical interventions on maintaining quality of life to the end."

The term quality of life was defined as the physical, psychological, social and spiritual domains of health that are influenced by a person's experiences, beliefs, expectations and perceptions.

The Mayo Clinic authors conclude their article: "We believe that the principles that have been so successful in improving the quality of life for hospice patients must be adopted in hospitals and related facilities such as nursing homes so that suffering can be relieved where the vast majority of Americans continue to die." Source: Mayo Clinic Proceedings, Volume 75 Number 12, December 2000.

Contact: John Murphy 507-284-5005 (days) 507-284-2511 (evenings) e-mail: newsbureau@mayo.edu

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