ESGE HEADLINE NEWS N°4

Application of genomics and proteomics
to the prevention of colorectal cancen

R Lambert

Synopsis

The completion of the Human Genome Project in 2003 led to significant developments in the field of genomics—the aim of which is to characterize all of the DNA coding elements that determine the phenotype of cells. Genomics can now be applied to issues involved in the hereditary transmission of diseases, as well as the molecular events that take place in the sequence of carcinogenesis.

The incidence of colorectal cancer and the mortality associated with it can be significantly reduced through the early detection and treatment of premalignant and malignant lesions. Colonoscopy is still the gold standard procedure, but there is growing interest in genomic approaches. Hereditary colorectal cancer includes syndromic familial diseases with autosomal-dominant Mendelian inheritance. It also includes nonsyndromic familial conditions in which multiple genetic variants interact with environmental factors. As emphasized by Burt and Neklason (2005), colorectal cancer occurs in three distinct situations:

Syndromic familial cases (less than 5% of the total)
Nonsyndromic familial clustering of cases (30% of the total)
Sporadic cases with no increased familial clustering (65% of the total)

When patients have provided informed consent, gene testing of blood samples is now carried out routinely for syndromic familial colorectal cancer in order to detect individuals who are at risk in a family. Identifying the specific mutation requires DNA sequencing. Once the mutation has been characterized, a simpler site-specific analysis can be carried out in the other members of the family.

In the other two groups, using a systematic questionnaire to assess a proband’s family antecedents helps distinguish between sporadic cancer and nonsyndromic familial cancer. The application of genomic techniques to tumor samples is now leading to more sophisticated analysis in both groups.

Identifying biomarkers for cancer depends on noninvasive tests that can identify alterations in the genes or proteins in the tumor. The reliability of these tests for early diagnosis and classification of hereditary and sporadic colorectal cancer is still a matter of debate.

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