Family risk of colorectal cancer

Kolorektalni karcinom (CRC) treći je po učestalosti, dok je drugi po smrtnosti u svijetu. Učestaliji je u razvijenim zemljama. Najčešće se pojavljuje sporadično, no studije pokazuju da postoji obiteljska sklonost u 30% slučajeva. U samo 3-6% slučajeva nađen je točan uzrok identifikacijom mutacija APC gena, MUTYH gena i mismatch repair gena (engl. mismatch repair genes, MMR). Najučestaliji, prema redoslijedu zastupljenosti, su Lynch sindrom i obiteljska adenomatozna polipoza (FAP) te rjeđi oblici kao što su MUTYH povezana polipoza, juvenilna polipoza, Peutz-Jeghersov sindrom itd. Najčešće povezane mutacije gena, u Lynch sindromu, su MLH1, MSH2, MSH6 te PMS2. Lynch sindrom je uzrok 2-4% karcinoma, zbog čega je najučestaliji oblik nasljednih kolorektalnih karcinoma. Karcinom se razvija u ranijoj životnoj dobi, negoli je to slučaj sa sporadičnim oblicima, a medijan dobi iznosi 45 godina. FAP je drugi najčešći CRC sindrom i čini oko 1% slučajeva CRC-a, a prepoznatljiv je zbog multiplih polipoznih promjena kolona. FAP je povezan s mutacijom APC gena. Iako je FAP povezan s autosomno dominantnim nasljeđivanjem, prosječno 30% oboljelih nema pozitivnu obiteljsku anamnezu te se bolest stoga povezuje s de novo mutacijama. Svi nasljedni oblici povezani su s ranijom pojavom CRC-a te je važno obiteljske srodnike oboljelih pratiti kako bi se bolest pravovremeno otkrila i uspješno liječila. U nasljednih oblika moguće je učiniti profilaktičku kolektomiju. Terapija aspirinom pokazala se uspješnom u prevenciji razvoja CRC-a u oboljelih od Lynch sindroma.Colorectal cancer is the third most common cancer and the second most common cause of death. The incidence is higher in developed countries. Most common cases of CRC are sporadic, while 30% has family history. Only 3-6% ofall cases are associated with genetic syndromes attributable to mutations of APC gene, MUTYH gene and mismatch repair genes (MMR). The most common are Lynch syndrome and Familial adenomatosis polyposis (FAP), while MUTYH associated polyposis, juvenile polyposis and Peutz-Jeghers syndrome are uncommon cases. Mutations, in Lynch syndrome, include MLH1, MSH2, MSH6 and PMS2. Lynch syndrome causes 2-4% of all CRC cases and is the most common of all family associated CRC. Carcinoma develops in younger age, than it is the case in sporadic forms and the median age at diagnosis is 45 years. FAP is the second most common CRC syndrome and makes approximately 1% of cases. It usually presents with development of multiple adenomas and is associated with the APC gene mutation. FAP is automosal dominantly inherited disease, but 30% of cases do not have a positive family history and are associated with de novo mutations. Inherited forms are connected with earlier disease development and it is important to screen for other family members in order to achieve better treatment outcome. It is possible to do profilactic colectomy in inherited individuals. Treatment with aspirine is efficient in preventing the development of CRC in individuals with Lynch syndrome