Redefining the Family Cancer History

There's a good chance that you are asking the wrong questions and not enough questions when it comes to taking family cancer histories. "It is not enough to ask 'Did anybody in your family die of cancer, yes or no?'" said Louise Strong, MD, Section Head of Clinical Cancer Genetics and Professor of Cancer Genetics at the University of Texas M.D. Anderson Cancer Center in Houston, TX.

"There is a whole list of questions you need to ask that most practitioners have not considered," she explained during yesterday's John and Marney Mathers Lecture. "If all you know is that relatives of your patient died of lung cancer, you are probably missing most of the important points."

The problem is a basic misunderstand of the role of genetics in cancer. Heredity is highly overrated as a cause of cancer for most individuals, Dr. Strong said. For most people in most populations, known genetic factors play little or no role in the development or treatment of their disease.

In the population as a whole, she explained, most cancer patients do not have a significant family history of cancer. A solid family history can help identify the exceptions.

In breast cancer, for example, only 10% of cases are linked to genetic factors. Another 15% to 20% of breast cancers may be influenced by heredity. That leaves at least 70% of breast cancers that appear to stem from causes other than heredity.

For ovarian cancer, about 10% of cases involve genetic defects. Two genes, BRCA1 and BRCA2, account for about 90% of those heritable cancers. HNPCC (hereditary nonpolyposis colorectal cancer) accounts for another 7%, with other genetic defects making up the balance. The other 90% of ovarian cancers are not related to known genetic defects.

But for some populations and some blood lines, genetic factors can be a vital link in the natural history of cancer. The role of the family history is to help identify those families in which genetics may play a role.

When a familial disease pattern is uncovered that may be related to some form of cancer, individuals can be screened to ascertain their individual risk. As genetic research progresses and more genomic links to cancer are found, the family history will become even more important as an early, noninvasive screening tool.

But even an apparent family proclivity to cancer may not be an indication for genetic screening. Screening for genetic defects is only useful and appropriate if the test can be adequately interpreted, Dr. Strong said.

Genetic testing should also be undertaken only if the results of the test will affect management of the patient or the disease and if testing is conducted with appropriate counseling.

A useful family history should include at least three generations, not just the patient sitting across the desk and her siblings or children. Not only does a three-generation pedigree include more individuals, it helps unmask effects such as gender differences.

Male carriers might go undetected unless the clinician asks about other generations that include female offspring in whom a genetic trait is expressed as cancer. A BRC1/2 gene might never reveal its presence in a generation of mostly-male siblings. Adding two more generations makes it more likely that the gene will be spotted from disease patterns in female family members.

Family histories should also include the age of diagnosis for all known cancers as well as the age and cause of death for all family members. Other cancer-specific details include primary and metastatic sites, any possible precursor lesions such as colon polyps, bilateral cancers, multiple cancers, any prophylactic surgeries, and known congenital abnormalities.

Family histories should be updated annually to provide a current picture as family members age and move into different risk groups for different types of cancer.

It is equally important to record ethnicity and race for all family members. Ashkenazi Jews, for example, have a higher incidence of BRCA1/2 than the general US population. Not surprisingly, Dr. Strong added, the population has an ovarian cancer rate of 40% compared to 12% across the entire United States.

Testing positive for BRCA1/2 also adds a 10% risk for developing prostate cancer as well as an increased risk for male breast cancer, pancreatic cancer, and Fallopian tube cancer in the Ashkenazi population. A single cancer of any type in the family in this population could be cause for genetic testing, Dr. Strong said. Other ethnic and racial groups have similar genetically linked susceptibilities.

HNPCC is another worrisome marker. Although the name and screening criteria all relate to colorectal cancer, HNPCC is also linked to cancers of the ovary, endometrium, stomach, and other organs.

Women carrying the HNPCC gene have an 80% increased risk for colorectal cancer, 60% for uterine cancer, and 15% for ovarian cancer. But the initial cancer presentation for women in the HNPCC population is 51% gynecologic disease and 49% gastrointestinal disease. Any person with three or more verified familial deaths from colorectal cancer should be screened, Dr. Strong said.

Genetic testing also has a positive flip side.

"One benefit of testing is being able to identify family members who do not carry the mutation and are at no higher risk than the general population," Dr. Strong said. "They can avoid the time, the bother, and the trauma of a lifetime of surveillance."