Cancer risk and overall survival in mismatch repair proficient hereditary non-polyposis colorectal cancer, Lynch syndrome and sporadic colorectal cancer.
Mismatch repair proficient hereditary non-polyposis colorectal cancer (MSS-HNPCC) encloses a heterogeneous group of families consisting of different unknown genetic syndromes and/or aggregations cases. The lack of information about the hereditability of cancer risk in these families makes it difficult to carry out an individualized Genetic Counseling. Therefore, deep description of such families becomes important for a better classification and search for underlying susceptibility causes. The aim of this study is to describe and compare the clinical, morphological features, tumor KRAS status and overall survival in MSS-HNPCC, Lynch and sporadic colorectal cancer. A total of 37 MSS-HNPCC families, 50 Lynch families and 612 sporadic CRC were included. Clinical and morphological data were evaluated by reviewing medical and pathology reports of 55, 69 and 102 tumors respectively. KRAS/BRAF status were detected by allele specific real-time PCR. Standardized incidence ratios (SIR) were calculated among 602 MSS-HNPCC relatives and 668 Lynch relatives. Main features distinguishing MSS-HNPCC were diagnosis age (55.1 ± 12.6), preferential distal location (76%), polyp detection (45%) and familial colorectal cancer incidence (SIR = 6.6). In addition, we found increased incidences rates for kidney, stomach and uterus tumors. KRAS mutation rates were similar in the study populations (48.8 ± 5.8) but higher than those described before by Sanger sequencing. MSS-HNPCC overall survival was similar to Lynch in B Dukes' stage tumors and between Lynch and sporadic in C stage tumors. Anatomical and morphological data of MSS-HNPCC are consistent with other described populations. Our studies disclose an increased HNPCC-extracolonic tumors incidence and improved overall survival in MSS-HNPCC families.
Laboratorio de Oncología Molecular, Servicio de Oncología Médica, Hospital Clínico San Carlos, IdISSC, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain, pilar_garre@hotmail.com.
Pilar
P
Garre
Lorena
L
Martín
Inmaculada
I
Bando
Alicia
A
Tosar
Patricia
P
Llovet
Julián
J
Sanz
Atocha
A
Romero
Miguel
M
de la Hoya
Eduardo
E
Díaz-Rubio
Trinidad
T
Caldés
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013577:Syndrome; D018631:ras Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins