Family health history as a 21st-century genetic tool.

Family history remains a crucial aspect of medical practice in 2007, even if it sometimes seems to be overshadowed by many exciting advances on the health care horizon. In this column, I will outline the reasons for a resurgence in interest in family history (and why it matters to internists), some of the ways in which "electronic tools" can improve the utility of family history, and a vision of the future role of family history in patient care.

Renewed Interest in Family History

Family history acts as a surrogate for complex genetic information in clinical care. In this era of genomic medicine, family history remains one of the most powerful predictors of risk for common disease. An example of this use of family history is seen routinely with coronary artery disease risk analysis. Without knowing the specifics of the genotype, we know that early coronary artery disease in a parent or sibling more than doubles a patient's risk of coronary artery disease. This knowledge allows a clinician to place increased emphasis on reducing modifiable risks.

Internists should take note that there has been a very important extension to the role of family history as a simple proxy for genetic information. Over the past decade, family history has emerged as a primary tool to guide decision making on the use of expensive genetic testing, such as BRCA1 and BRCA2 testing. In fact, the United States Preventive Services Task Force (USPSTF) guidelines from September 2005 (www.ahrq.gov/clinic/uspstf/uspsbrgen.htm) recommend "that women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing."

Implicit in that recommendation is an expectation that a comprehensive family history is obtained and analyzed. In order to fulfill this USPSTF recommendation, providers will need comprehensive family history data that include all first- and second-degree relatives. Collection of such comprehensive data is a 10- to 20-minute task. Failure to acquire this data and analyze these pedigrees could mean a failure to diagnose those estimated 1 in 350 women who carry one of the BRCA gene mutations.

BRCA-related family history analysis in primary care is just the first of many potential new applications for family history to land on the primary care agenda. Only one thing appears clear in this emerging arena: It will be impossible for any provider to comply with this kind of recommendation without computer support.

Electronic Tools for Family History

When it comes to family history acquisition, it is a matter of simple mathematics. Here is the equation: 16 - 15 = 10. Those numbers again: 16 is an average estimated length of time, in minutes, per visit in a primary care practice; 15 is the estimated length of time, in minutes, needed to acquire an annotated three-generation pedigree; 10 is the estimated percentage of patient charts that contain complete family histories. Obviously, without pushing other items off the agenda, there simply is not enough time to acquire detailed family history data during routine visits.

The time conundrum can be partially addressed by delegating the task of primary data collection to patients. Widely available electronic tools, such as the U.S. Surgeon General's "My Family Health Portrait" (https://familyhistory.hhs.gov), allow patients to gather and organize data in an editable format. With this and other tools available to patients, the provider can now entrust primary data entry to the patient so that the provider's time can be spent on data editing and analysis. Currently, manual analysis of the data will be needed, but multiple tools are in development to provide computer-generated decision support for risk analysis.

The (Near) Future of Family History

Patients are currently able to obtain genetic sequence results without physician consultation through direct-to-consumer tests that promise risk prediction for common diseases based on small DNA sequence variants. Some have suggested that full genome sequencing of individuals will be commercially available in as little as 3-5 years. With this rapidly advancing technology, how will we as providers begin to put all of this DNA sequence data into perspective for the patient? Family history will take on a new role as we increasingly find ourselves faced with that question.

Patients will ask, "My test results show a genetic variant. What does that mean for me?" One analytic approach to that discussion will start by exploring how those same variants play out in the patient's closest relatives. Thus, comprehensive family history databases, generated by patients and their families and refined by health care providers, are likely to become crucial tools in the assessment of individual risk based on DNA results. When that happens, we will have gone full circle from using family history to decide whom to test, to using family history to decide what to do with the genetic test results in hand.

Family history is in fact the oldest genetic analysis tool available, but its greatest days may lie ahead.

DR. MURRAY is the clinical chief of genetics at Brigham and Women's Hospital and an instructor at Harvard Medical School, Boston.

BY MICHAEL F. MURRAY, M.D.