Hereditary colorectal cancer syndromes in Estonia
Date
2023-11-29
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Abstract
Kolorektaal- ehk jämesoolevähki defineeritakse kui pahaloomulist kasvajat, mis saab alguse käär- või pärasoolest. Kuni 10% jämesoolevähi juhtudest on pärilikud. Eestis on jämesoolevähk üks levinumaid pahaloomulisi kasvajaid, olles ka sage vähisurma põhjus. Enne 2012. aastat oli Eestis võimalik teostada vaid üksikuid päriliku jämesoolevähi geneetilisi uuringuid. Teistest diagnostilistest meetoditest oli põhiline MMR (mismatch repair) geenide immuunhistokeemiline (IHK) uuring. Tänapäeval teostatakse vastavalt näidustustele geeniuuringuid kasutades paljude geenide samaaegset sekveneerimist, seda nii pärilike kasvajasündroomide diagnostikaks verest kui ka kasvajakoest eelkõige raviotsuste tegemiseks. Geneetiliste uuringute roll on oluline ka tervete pereliikmete vähiriskide hindamisel, mis võimaldab rakendada jälgimisprogramme ning seeläbi langetada vähisuremust.
Käesolevas uuringus hindasime esiteks rutiinse töö käigus teostatud sekveneerimise analüüside diagnostilist efektiivsust jämesoolevähiga patsientidel, ning selgus, et 22,3% esines haigus-seoseline pärilik geenimuutus. Lynchi sündroomi (LS) sünnilevimus oli Eestis aastatel 1930-2003 hinnanguliselt 1:8 638 (95% CI: 1:9 859-7 588). 10a jooksul on LS levimus tõusnud ligi kuus korda, tulenedes eelkõige parematest diagnostilistest võimalustest ning teadlikkuse tõusust. Võrreldes soolevähist haaratud indiviidiga saavad pereliikmed LS diagnoosi keskmiselt 8 aastat varem, mis võimaldab varasemat ennetust. MMR geenide IHK analüüsi diagnostilise efektiivsuse hindamisel >50a kolorektaalvähiga patsientide hulgas leidsime, et üle pooltel juhtudest kinnitus LS diagnoos, mistõttu on edaspidi soovitatav MMR IHK uuringuid teostada kõigile kolorektaalvähi patsientidele sõltumata vanusest. AXIN2-ga seotud oligodontia-kolorektaalvähi sündroomi uuringud näitasid, et suulaelõhe võib olla antud sündroomi uus tunnus, kuid vajalikud on täiendavad uuringud fenotüübi osas ning koostöö patsientide jälgimisjuhendi koostamiseks
Colorectal cancer (CRC) is defined as a cancer that starts from the colon or rectum. Up to 10% of CRC cases are hereditary. In Estonia, CRC is one of the most common cancers as well as a frequent cause of cancer-related death. Until 2012, only a few genetic tests were available for hereditary CRC. MMR (mismatch repair) genes immunohistochemistry (IHC) was another diagnostic method available. Today, sequencing of many genes simultaneously is used for diagnostics: analysis from blood is used to diagnose hereditary CRC syndromes and for treatment-related decisions cancer tissue is used. Furthermore, genetic testing is also important in healthy family members to detect individuals at risk and survey them accordingly to decrease cancer-related death. In this study we estimated the diagnostic efficacy of sequencing in the routine clinical setting in CRC patients and found that 22.3% had a disease-causing hereditary gene variant. Birth prevalence of Lynch syndrome (LS) in 1930-2003 in Estonia was 1:8 638 (95% CI: 1:9 859-7 588). In ten years LS prevalence has risen approximately six times, which is probably the result of better diagnostic opportunities and knowledge. Compared to cancer patients, their family members are diagnosed approximately eight years earlier leading to earlier surveillance. Analysing MMR IHC diagnostic efficacy among CRC patients aged >50 years, in more than half of the cases LS was diagnosed. Because of that, we suggest MMR IHC for all CRC patients independent of their age. AXIN2-related oligodontia-colorectal cancer syndrome studies showed that cleft palate might be a new clinical feature of this syndrome. Still, further studies are needed to investigate the phenotype and develop a surveillance plan.
Colorectal cancer (CRC) is defined as a cancer that starts from the colon or rectum. Up to 10% of CRC cases are hereditary. In Estonia, CRC is one of the most common cancers as well as a frequent cause of cancer-related death. Until 2012, only a few genetic tests were available for hereditary CRC. MMR (mismatch repair) genes immunohistochemistry (IHC) was another diagnostic method available. Today, sequencing of many genes simultaneously is used for diagnostics: analysis from blood is used to diagnose hereditary CRC syndromes and for treatment-related decisions cancer tissue is used. Furthermore, genetic testing is also important in healthy family members to detect individuals at risk and survey them accordingly to decrease cancer-related death. In this study we estimated the diagnostic efficacy of sequencing in the routine clinical setting in CRC patients and found that 22.3% had a disease-causing hereditary gene variant. Birth prevalence of Lynch syndrome (LS) in 1930-2003 in Estonia was 1:8 638 (95% CI: 1:9 859-7 588). In ten years LS prevalence has risen approximately six times, which is probably the result of better diagnostic opportunities and knowledge. Compared to cancer patients, their family members are diagnosed approximately eight years earlier leading to earlier surveillance. Analysing MMR IHC diagnostic efficacy among CRC patients aged >50 years, in more than half of the cases LS was diagnosed. Because of that, we suggest MMR IHC for all CRC patients independent of their age. AXIN2-related oligodontia-colorectal cancer syndrome studies showed that cleft palate might be a new clinical feature of this syndrome. Still, further studies are needed to investigate the phenotype and develop a surveillance plan.
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Keywords
colorectal cancer, hereditary diseases, medical genetics, Estonia