胃と腸45巻13号

2010年12月発行

今月の主題 遺伝性消化管疾患の特徴と長期経過 主題

家族性大腸腺腫症―家族性大腸腺腫症の長期経過

著者： 前畠裕司¹ 松本主之¹ 浅野光一¹ 藤澤律子¹ 江㟢幹宏¹ 中村昌太郎¹ 藤田恒平² 平橋美奈子² 植木隆³ 飯田三雄¹⁴

所属機関： ¹九州大学大学院病態機能内科学 ²九州大学大学院形態機能病理学 ³九州大学大学院臨床腫瘍外科 ⁴公立学校共済組合九州中央病院

ページ範囲：P.2026 - P.2037

要旨　自験家族性大腸腺腫症（FAP）91例の診断時消化管徴候，および長期経過観察中における消化管病変の推移と悪性腫瘍を遡及的に検討し，APC遺伝子型と対比した．その結果，密生型大腸腺腫症，十二指腸非乳頭部腺腫が3´側変異群に高率に発生しており，遺伝子型と臨床徴候の関係が示唆された．一方，3´側変異群で胃腺腫と残存直腸腺腫の進行例が多かった．また，大腸癌以外の悪性腫瘍として，3´側変異群で肝細胞芽腫と致死的デスモイドがみられたが，そのほかの悪性腫瘍は3群で有意差なくほぼ均等に発生していた．以上より，FAPにおいて臨床徴候と腸管病変の推移はAPCの遺伝子型の影響を受けるが，本症の長期管理では遺伝子型に関係なく全身のサーベイランスが必要と考えられた．

参考文献

1）Bussey HJR. Familial polyposis coli. Johns Hopkins University Press, Baltimore, 1975

2）飯田三雄，小堀陽一郎，水野充，他．家族性大腸腺腫症の大腸外腫瘍状病変．胃と腸 35 : 327-336, 2000

3）松本主之，矢鳴律子，小堀陽一郎，他．家族性大腸腺腫症の臨床徴候と遺伝子変異の関係．胃と腸 39 : 1099-1112, 2004

4）Nakamura S, Matsumoto T, Kobori Y, et al. Impact of Helicobacter pylori infection and mucosal atrophy on gastric lesions in patients with familial adenomatous polyposis. Gut 51 : 485-489, 2002

5）Iida M, Matsui T, Itoh H, et al. The value of push-type jejunal endoscopy in familial adenomatosis coli/Gardner's syndrome. Am J Gastroenterol 85 : 1346-1348, 1990

6）Matsumoto T, Esaki M, Moriyama T, et al. Comparison of capsule endoscopy and enteroscopy with the double-balloon method in patients with obscure bleeding and polyposis. Endoscopy 37 : 827-832, 2005

7）Matsumoto T, Esaki M, Yanaru-Fujisawa R, et al. Small-intestinal involvement in familial adenomatous polyposis : evaluation by double-balloon endoscopy and intraoperative enteroscopy. Gastrointest Endosc 68 : 911-919, 2008

8）Yanaru-Fujisawa R, Matsumoto T, Ushijima Y, et al. Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis. Clin Genet 73 : 545-553, 2008

9）Iwata T, Mishima Y, Utsunomiya J. The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment Ann Surg 217 : 101-108, 1993

10）Nishisho I, Nakamura Y, Miyoshi Y, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253 : 665-669, 1991

11）Soravia C, Berk T, Madlensky L, et al. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet 62 : 1290-1301, 1998

12）Nagase H, Miyoshi Y, Horii A, et al. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Res 52 : 4055-4057, 1992

13）Iida M, Yao T, Itoh H, et al. Natural history of fundic gland polyposis in patients with familial adenomatosis coli/Gardner's syndrome. Gastroenterology 89 : 1021-1025, 1985

14）Iida M, Yao T, ltoh H, et al. Natural history of gastric adenomas in patients with familial adenomatosis coli/Gardner's syndrome. Cancer 61 : 605-611, 1988

15）Iida M, Yao T, ltoh H, et al. Natural history of duodenal lesions in Japanese patients with familial adenomatosis coli（Gardner's syndrome）. Gastroenterology 96 : 1301-1306, 1989

16）飯田三雄，檜沢一興，松本主之，他．家族性大腸腺腫症における胃・十二指腸病変の長期経過．胃と腸 32 : 563-576, 1997

17）Matsumoto T, lida M, Nakamura S, et al. Natural history of ampullary adenoma in familial adenomatous polyposis : reconfirmation of benign nature during extended surveillance. Am J Gastroenterol 95 : 1557-1562, 2000

18）Toyooka M, Konishi M, Kikuchi-Yanoshita R, et al. Somatic mutations of the adenomatous polyposis coli gene in gastroduodenal tumors from patients with familial adenomatous polyposis. Cancer Res 55 : 3165-3170, 1995

19）Enomoto M, Konishi M, Iwama T, et al. The relationship between frequencies of extracolonic manifestations and the position of APC germline mutation in patients with familial adenomatous polyposis. Jpn J Clin Oncol 30 : 82-88, 2000

20）Jagelman DG, DeCosse JJ, Bussey HJ. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1 : 1149-1151, 1988

21）Offerhaus GJ, Giardiello FM, Krush AJ, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 102 : 1980-1982, 1992

22）Abraham SC, Nobukawa B, Giardiello FM, et al. Fundic gland polyps in familial adenomatous polyposis : neoplasms with frequent somatic adenomatous polyposis coli gene alterations. Am J Pathol 157 : 747-754, 2000

23）Zwick A, Munir M, Ryan CK, et al. Gastric adenocarcinoma and dysplasia in fundic gland polyps of a patient with attenuated adenomatous polyposis coli. Gastroenterology 113 : 659-663, 1997

24）Hofgärtner WT, Thorp M, Ramus MW, et al. Gastric adenocarcinoma associated with fundic gland polyps in a patient with attenuated familial adenomatous polyposis. Am J Gastroenterol 94 : 2275-2281, 1999

25）Wu JS, Paul P, McGannon EA, et al. APC genotype, polyp number, and surgical options in familial adenomatous polyposis. Ann Surg 227 : 57-62, 1998

26）Nieuwenhuis MH, Mathus-Vliegen LM, Slors FJ, et al. Genotype-phenotype correlations as a guide in the management of familial adenomatous polyposis. Clin Gastroenterol Hepatol 5 : 374-378, 2007

27）Valanzano R, Ficari F, Curia MC, et al. Balance between endoscopic and genetic information in the choice of ileorectal anastomosis for familial adenomatous polyposis. J Surg Oncol 95 : 28-33, 2007

28）Vasen HF, Möslein G, Alonso A, et al. Guidelines for the clinical management of familial adenomatous polyposis（FAP）. Gut 57 : 704-713, 2008

29）Matsumoto T, Iida M, Tada S, et al. Early detection of nonpolypoid cancers in the rectal remnant in patients with familial adenomatous polyposis/Gardner's syndrome. Cancer 74 : 12-15, 1994

30）Soravia C, Klein L, Berk T, et al. Comparison of ileal pouch-anal anastomosis and ileorectal anastomosis in patients with familial adenomatous polyposis. Dis Colon Rectum 42 : 1028-1033, 1999

31）Vasen HF, van Duijvendijk P, Buskens E, et al. Decision analysis in the surgical treatment of patients with familial adenomatous polyposis : a Dutch-Scandinavian collaborative study including 659 patients. Gut 49 : 231-235, 2001

32）Yamaguchi T, Yamamoto S, Fujita S, et al. Long-term outcome of metachronous rectal cancer following ileorectal anastomosis for familial adenomatous polyposis. J Gastrointest Surg 14 : 500-505, 2010

33）Bertario L, Russo A, Radice P, et al. Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis. Ann Surg 231 : 538-543, 2000

34）Bülow C, Vasen H, Järvinen H, et al. Ileorectal anastomosis is appropriate for a subset of patients with familial adenomatous polyposis. Gastroenterology 119 ; 1454-1460, 2000

35）Nieuwenhuis MH, Bülow S, Björk J, et al. Genotype predicting phenotype in familial adenomatous polyposis : a practical application to the choice of surgery. Dis Colon Rectum 52 : 1259-1263, 2009

36）Matsumoto T, Iida M, Kobori Y, et al. Genetic predisposition to clinical manifestations in familial adenomatous polyposis with special reference to duodenal lesions. Am J Gastroenterol 97 : 180-185, 2002

37）Björk J, Akerbrant H, Iselius L, et al. Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis : cumulative risks and APC gene mutations. Gastroenterology 121 : 1127-1135, 2001

38）Groves C, Lamlum H, Crabtree M, et al. Mutation cluster region, association between germline and somatic mutations and genotype-phenotype correlation in upper gastrointestinal familial adenomatous polyposis. Am J Pathol 160 : 2055-2061, 2002

39）Saurin JC, Ligneau B, Ponchon T, et al. The influence of mutation site and age on the severity of duodenal polyposis in patients with familial adenomatous polyposis. Gastrointest Endosc 55 : 342-347, 2002

40）Leggett BA, Young JP, Biden K, et al. Severe upper gastrointestinal polyposis associated with sparse colonic polyposis in a familial adenomatous polyposis family with an APC mutation at codon 1520. Gut 41 : 518-521, 1997

41）Matsumoto T, Iida M, Kobori Y, et al. Progressive duodenal adenomatosis in a familial adenomatous polyposis pedigree with APC mutation at codon 1556. Dis Colon Rectum 45 : 229-233, 2002

42）Umeno J, Matsumoto T, Esaki M, et al. Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis. Int J Colorectal Dis 25 : 293-301, 2010

43）Sturt NJ, Gallagher MC, Bassett P, et al. Evidence for genetic predisposition to desmoid tumours in familial adenomatous polyposis independent of the germline APC mutation. Gut 53 : 1832-1836, 2004

44）Bala S, Wünsch PH, Ballhausen WG. Childhood hepatocellular adenoma in familial adenomatous polyposis : mutations in adenomatous polyposis coli gene and p53. Gastroenterology 112 : 919-922, 1997