New genes emerging for colorectal cancer predisposition

Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic differences.Mendelian syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common forms.Excluding hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause.CRC can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect.So far,30 common,low-penetrance susceptibility variants have been identified for CRC.Recently,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition.By using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis.

Identification of Lynch syndrome: How should we proceed in the 21^(st) century?

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. This is especially relevant since colonoscopy has been proven effective for reducing colorectal cancer incidence and mortality in individuals at-risk for this disorder. In this manuscript, we summarize the most significant contributions to this important issue that have appearedin the last few years.

Colorectal cancer prognosis twenty years later

AIM:To evaluate changes in colorectal cancer(CRC) survival over the last 20 years.METHODS:We compared two groups of consecutive CRC patients that were prospectively recruited:Group Ⅰincluded 1990 patients diagnosed between 1980 and 1994.GroupⅡincluded 871 patients diagnosed in 2001.RESULTS:The average follow up time was 21 mo(1-229)for GroupⅠand 50 mo(1-73.4)for GroupⅡ.Overall median survival was significantly longer in Group Ⅱthan in GroupⅠ(73 mo vs 25 mo,P<0.001)and the difference was significant for all tumor stages.Post surgical mortality was 8% for GroupⅠand 2% for Group Ⅱ(P<0.001).Only 17% of GroupⅠpatients received chemotherapy compared with 50% of GroupⅡpatients(P<0.001).CONCLUSION:Survival in colorectal cancer patients has doubled over the past 20 years.This increase seems to be partly due to the generalization in the administration of chemotherapy and to the decrease of post surgical mortality.

Rare germline copy number variants in colorectal cancer predisposition characterized by exome sequencing analysis

Colorectal cancer （CRC） is one of the most common neoplasms and an important cause of mortality worldwide （http：//globocan. iarc.fr]）. Approximately 35% of the variation in CRC susceptibility is likely due to heritable factors （Lichtenstein et al., 2000}. Genetic variations in the human genome include single nucleotide variants （SNVs）, short insertions and deletions, and larger structural variants resulting in gain or loss of genomic DNA larger than 1 kb, such as copy number variants （CNVs）. Leaving aside the importance of CNVs in sporadic tumor development, these variants can also be present in the germline DNA of healthy individuals from the general population and be considered polymorphic.