title: Identification of predictive factors for the occurrence of predisposing MLH1 and MSH2 germline mutations among Sardinian patients with colorectal carcinoma.
abstract: Factors predictive of carrying MLH1 and MSH2 germline mutations in patients with colorectal cancer (CRC) are as yet unknown. The aim of this population-based study, was to further define the role of MLH1/MSH2 mutations through an evaluation clinic program with 362 consecutive Sardinian CRC patients. Eight MLH1/MSH2 germline mutations were detected in 21 (6%) patients. Examining family cancer history, MLH1/MSH2 mutations were found in 14/48 (29.2%) probands from CRC families and, among them, in 10/13 (76.9%) families fulfilling the Amsterdam criteria. The patients with low familial recurrence (two CRCs in the family) presented a much lower frequency of MLH1/MSH2 mutations (2/55; 3.6%). Significantly higher rates of MLH1/MSH2 mutations were found in patients with age of onset 45 years (P=0.012) or with 3 affected family members (P=0.009). While no significant predictive value was found for the presence of endometrial cancer within the family, earlier age of diagnosis and/or familial CRC recurrence should be considered as strong predictors for the occurrence of MLH1/MSH2 mutations, and therefore useful in recommending CRC patients for genetic testing.
authors.affiliation: Istituto di Chimica Biomolecolare-Sezione di Sassari, CNR, Traversa La Crucca, 3-Reg. Baldinca, 07040 Li Punti-Sassari (SS), Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Colombino
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: Maria P
authors.initials: MP
authors.lastname: Satta
authors.forename: Paola
authors.initials: P
authors.lastname: Baldinu
authors.forename: Milena
authors.initials: M
authors.lastname: Casula
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.forename: Marina
authors.initials: M
authors.lastname: Pisano
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sini
authors.forename: Angelo
authors.initials: A
authors.lastname: Deiana
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein