TABLE 2-3 Genetic Variants Used for Disease Diagnosis and Treatment

Disease/Condition Genetic Factor
Hyperlipidemia susceptibility LDL receptor gene mutation

Breast/ovarian cancer susceptibility

BRCA1/BRCA2 mutation

Lung cancer treatment

KRAS, EGFR, EML4-ALK, HER2, BRAF, MET, AKT1, MAP2K1, PIKCA mutations

Maturity-onset diabetes of the young classification

chromosome 7, glucokinase, chromosome 12, hepatic nuclear factor 1-alpha, etc., mutations

SOURCE: Data derived from IOM, 2011.

Center, 2008; Manolio, 2010; Pearson and Manolio, 2008). The genetic factors associated with a variety of diseases are now known and can be used in diagnosis and treatment (see Table 2-3) (IOM, 2011). These new discoveries highlight the magnitude of individual variation, adding numerous factors that clinicians may have to consider when evaluating the utility of different treatments and interventions.

One area in which advances in genetics have led to a more sophisticated understanding of disease is the ability to distinguish among different types of lung cancers. Traditionally, lung cancers were divided into types—small-cell and non-small-cell—based on the tumor’s histological appearance. However, genetic discoveries have allowed histological classification to be replaced by classification based on the cancer cells’ genetic profile, and more specifically, the genetic mutations that are the molecular drivers of cancer cell proliferation (see Figure 2-6). In 1987, one driver mutation, KRAS, was discovered, and another, EGFR, was discovered in 2004. Since then, knowledge of the molecular drivers of non-small-cell lung cancer has increased dramatically; by 2009, nine different driver mutations had been identified (IOM, 2011). While the development of therapies targeting specific driver mutations is just beginning, genetic classification of diseases holds great promise for tailoring care to patients’ genetic variations.

An example of a case in which genetics are beginning to have a substantial impact on care is maturity-onset diabetes of the young (MODY). This rare form of diabetes, generally diagnosed in later adolescence or early adulthood, often is undiagnosed and is easily confused with other forms of diabetes. Treating patients with this condition used to be difficult because different patients would respond very differently to various treatments (O’Rahilly, 2009). With improved genetic understanding, however, MODY was found to be a cluster of diseases, each entailing a specific genetic abnormality. To date, six different varieties of this disease have been identified,



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