Abstract
BackgroundHeritable factors are well known to increase the risk of cancer in families. Known susceptibility genes account for a small proportion of all colorectal cancer cases. The aim of this study was to identify the genetic background in a family suggested to segregate a dominant cancer syndrome with a high risk of rectal- and gastric cancer. We performed whole exome sequencing in three family members, 2 with rectal cancer and 1 with gastric cancer and followed it up in additional family members, other patients and controls.ResultsWe identified 12 novel non-synonymous single nucleotide variants, which were shared among 5 affected members of this family. The mutations were found in 12 different genes; DZIP1L, PCOLCE2, IGSF10, SUCNR1, OR13C8, EPB41L4B, SEC16A, NOTCH1, TAS2R7, SF3A1, GAL3ST1, and TRIOBP. None of the mutations was suggested as a high penetrant mutation. It was not possible to completely rule out any of the mutations as contributing to disease, although seven were more unlikely than the others. Neither did we rule out the effect of all thousands of intronic, intergenic and synonymous variants shared between the three persons used for exome sequencing.ConclusionsWe propose this family, suggested to segregate dominant disease, could be an example of complex inheritance.
Highlights
Heritable factors are well known to increase the risk of cancer in families
Epidemiological studies have estimated that the risk of developing colorectal cancer in first-degree relatives of patients diagnosed with cancer is increased by two to four-fold [1]
Several hereditary syndromes, such as Familial Adenomatous Polyposis (FAP) and Lynch syndrome, are known where the risk of cancer development can be as high as 100 %
Summary
Heritable factors are well known to increase the risk of cancer in families. Known susceptibility genes account for a small proportion of all colorectal cancer cases. Epidemiological studies have estimated that the risk of developing colorectal cancer in first-degree relatives of patients diagnosed with cancer is increased by two to four-fold [1] Several hereditary syndromes, such as Familial Adenomatous Polyposis (FAP) and Lynch syndrome, are known where the risk of cancer development can be as high as 100 %. No hereditary cause has been identified in most of the families with familial cancer Even though these families show empirical evidence of an increased risk of developing cancer, most of them do not fulfill the criteria for FAP or Lynch syndrome [2]. This is indicative of additional genes predisposing to cancer
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