Mini-Review and PerspectiveConcepts in Familial Colorectal Cancer: Where Do We Stand and What Is the Future?
Section snippets
Genetics
The heterogeneous nature of nonsyndromic familial CRC suggests the coexistence of diverse pathogenic mechanisms. Potential genetic models range from a handful of modest risk alleles to a very large number of small risk alleles, which is the so-called polygenic model of complex diseases.8
Several candidate genes have been considered. In an initial approach, research efforts were made to investigate the involvement of more common, less penetrant genetic variants of known genes responsible for the
Screening Considerations
First-degree relatives of patients with CRC have a 2- to 3-fold increased risk of developing this neoplasm, compared with the overall population (reviewed by Burt and Neklason2; Figure 1). Likewise, it has been found that CRC risk in persons with an affected first-degree relative is approximately the same at age 40 as the general population at age 50.35
From a clinical perspective, the familial risk of CRC depends mainly on the number of relatives, the kinship, and the age of cancer diagnosis.
Therapeutic Implications
Many studies have demonstrated that family history of CRC increases the risk of developing the disease by 2- or 3-fold.35, 37, 41 However, there is controversy over whether a family history of CRC affects the outcome of patients with established disease. A recent study42 demonstrated that a family history of CRC is associated with a significant reduction in cancer recurrence and death among patients with stage III colon cancer receiving adjuvant chemotherapy. In fact, compared with patients
Conclusion
Although it is likely that syndromic entities with a Mendelian inheritance may emerge from the heterogeneous category of familial CRC, predisposition to such a neoplasm in this setting seems to be due to common, low-penetrance genetic components. Genetic testing involving the identified susceptibility genes or others could soon become part of the clinical armamentarium for assessing CRC risk and determining the optimal diagnostic, therapeutic, and preventive approaches. Indeed, identification
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Conflicts of interestThe authors disclose no conflicts.
Funding Supported by grants from the Ministerio de Educación y Ciencia (SAF 07-64873), Asociación Española contra el Cáncer (Fundación and Junta de Barcelona), Fondo de Investigación Sanitaria (05/0071 and 08/0024), Acción Transversal de Cáncer (Instituto de Salud Carlos III), Fundación Olga Torres, and Fundación de Investigación Médica Mutua Madrileña,. CIBERehd is funded by the Instituto de Salud Carlos III.