家族性大腸腺腫症の臨床徴候と遺伝子変異の関係

Genotype-Phenotype Correlation in Familial Adenomatous Polyposis

要旨　自験家族性大腸腺腫症（FAP）52例の臨床徴候とAPC遺伝子変異の関係を検討した．臨床徴候をエクソン10までの5´側変異群，エクソン11より近位側の3´側変異群，変異陰性群で比較すると，密生型大腸腺腫症，十二指腸非乳頭部腺腫，骨腫，網膜色素上皮過形成の陽性率が3´側変異群で最も高かった．一方，3群間で十二指腸腺腫症と残存直腸の経過に明らかな違いを指摘できなかったが，大腸癌以外の悪性腫瘍として3´側変異群では十二指腸・小腸癌，および肝細胞芽腫が発生したのに対し，変異陰性群では膵癌，胃癌，直腸カルチノイドが発生していた．同一家系内の複数例では，デスモイド腫瘍，胃底腺ポリポーシス，十二指腸乳頭部腺腫の発生に乖離がみられた．以上より，FAPにおける網膜色素上皮過形成，骨腫，十二指腸非乳頭腺部腺腫，および大腸癌以外の悪性腫瘍はAPC遺伝子変異に影響を受ける可能性が示唆された．

　We examined comparatively phenotypic features and genotype of the APC gene in 52 patients with familial adenomatous polyposis (FAP). When the patients were divided into the 5´ mutation group, the 3´ mutation group and mutation-negative group according to the result of the protein truncation test, profuse polyposis, non-ampullary duodenal adenomatosis, osteoma, and congenital hypertrophy of the retinal pigment epithelium (CHRPE) were most frequently found in the 3´ mutation group. However, the clinical courses of adenomatosis in the duodenum and in the rectal remnant were similar among the three groups. In the 3´ mutation group, cancers of the small intestine and hepatoblastoma were identified as extracolonic malignant neoplasms, while pancreatic cancer, gastric cancer, and rectal carcinoid occurred in the mutation-negative group. Desmoid tumors, gastric fundic gland polyposis and ampullary adenomas were unable to be segregated as familial. These findings suggest that CHRPE, osteoma, nonampullary duodenal adenoma, and extracolonic malignant neoplasm are phenotypes of FAP, which are influenced by APC gene mutation.

　1) Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan