OC.08.1 NATURAL HISTORY OF LYNCH SYNDROME IN NORTHEASTERN ITALY

Background and aim: Lynch Syndrome (LS) is an inherited cancer predisposition bringing about 2-3% of all new cases of ColoRectal Cancer (CRC), caused by mutation in mismatch repair (MMR) genes. LS patients have a lifetime risk to develop a CRC up to 75% in men and 52% in women and an Endometrial Carcinoma (EC) up to 71%. The cancer spectrum involves other organs (ovary, stomach, urinary tract and small bowel), but with a lower risk. Material and methods: Families included in the study were registered in the “Registro Tumori Ereditari del colon-retto”, settled since 1992 at our Institution. Pathogenic mutations in MSH2, MLH1 and MSH6 were identified in 37 unrelated families. We tested 251 members of the families including the probands: 113 (45%) were gene carries (44M and 69F) and 138 were wild-type. 25 families displayed mutation in MSH2, 11 families in MLH1 and one in MSH6. Surveillance program included colonoscopy from age 22 with an interval of 1-2 years, abdominal ultrasound, urine cytology every two years and upper GI endoscopy every 4 years from age 35. For women, the gynecological work out included transvaginal ultrasonography and endometrial biopsy every two years from 30-35 years. Results: The first cancer diagnosed was CRC in almost all males. EC and CRC were equally diagnosed in women. The number of CRC increased abruptly until age 40 and decreased slowly with aging. Extra-colonic cancers (EXC) increased from age 50. 78 (69%) patients developed at least one cancer: 57 (50.4%) CRC and 32 female patients (46.4%) EC. Cancer of any type occurred in all patients over age 60. 66 (56.4%) had multiple primary cancers related to aging. A progressive increase of CRC and EXC was seen and patients with six EXC had a mean age of 74 years. The deaths registered were 11 (9.7%): 2 (1.7%) for pancreatic cancer and 9 (7.9%) for other diseases between 69 and 83 of age. Colonic surveillance lasted for an average period of 10.5 years (2-22 years). 5 patients (4.4%) out of 113 had CRC at stage T1 (2 pts), T2 (2 pts) and T2N1 (1 pt) and 38 (33.6%) patients had 121 advanced adenomas. Conclusions: Getting old, all LS patients displayed at least one cancer and more than 50% had multiple primary cancers. Colectomy with ileo-rectum anastomosis is the therapy of choice at first CRC diagnosed to avoid any further surgical procedures for that disease. Surveillance of organ targets should be included in long survivors from CRC.