Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.204
Revised: August 17, 2013
Accepted: September 15, 2013
Published online: January 7, 2014
AIM: To evaluate the risk associated with variants of the UNC5C gene recently suspected to predispose to familial colorectal cancer (CRC).
METHODS: We screened patients with familial CRC forms as well as patients with sporadic CRCs. In a first time, we analyzed exon 11 of the UNC5C gene in 120 unrelated patients with suspected hereditary CRC, 58 patients with suspected Lynch-associated cancer or polyposis, and 132 index cases of Lynch syndrome families with a characterized mutation in a DNA mismatch repair (MMR). Next, 1023 patients with sporadic CRC and 1121 healthy individuals were screened for the variants identified in patients with familial cancer.
RESULTS: Of 120 patients with familial CRC of unknown etiology, one carried the previously reported mis-sense mutation p.Arg603Cys (R603C) and another exhibited the unreported variant of unknown significance p.Thr617Ile (T617I). The p.Ala628Lys (A628K) mutation previously described as the main UNC5C risk variant for familial CRC was not detected in any cases of familial CRC of unknown etiology, but was present in a patient with familial gastric cancer and in two Lynch syndrome patients in co-occurrence with MMR mutations. A statistically non-significant increase in cancer risk was identified in familial CRC and/or other Lynch-associated cancers (1/178 patients vs 2/1121 healthy controls, OR = 3.2, 95%CI: 0.29-35.05, P = 0.348) and in sporadic CRCs (4/1023 patients vs 2/1121 healthy controls, OR = 2.2, 95%CI: 0.40-12.02, P = 0.364).
CONCLUSION: We confirm that UNC5C mutations are very rare in familial and sporadic CRCs, but further investigations are needed to justify routine UNC5C testing for diagnostic purposes.
Core tip:UNC5C was recently described as a new gene potentially predisposing to familial forms of colorectal cancer (CRC). In order to evaluate the risk of CRC associated with the variants of UNC5C exon 11 suggested to underlie this predisposition, we screened both patients with familial CRC forms of hitherto unknown etiology, and patients with sporadic CRCs. Overall, we confirm that UNC5C mutations are very rare in familial and sporadic forms of CRC. Further identifications of families with UNC5C mutations are needed to justify routine UNC5C testing in patients with CRC or gastric cancer for potential genetic counseling purposes.