臨床検査51巻12号

2007年11月発行

特集 遺伝子検査―診断とリスクファクター 3．遺伝子診断の実際

1) 悪性腫瘍　(5)大腸癌―自然排泄便からの大腸癌細胞分離と遺伝子診断の実際

著者： 古賀宣勝¹ 松村保広¹

所属機関： ¹国立がんセンター東病院 臨床開発センターがん治療開発部

ページ範囲：P.1376 - P.1382

背景

1．大腸癌とは

　世界において大腸癌は全悪性腫瘍のうち，肺癌についで第2位の年間約1,065万人が罹患し，肺癌，胃癌についで第3位の約62万人が死亡する癌である(2002年，WHO統計)．わが国においても生活様式の欧米化に伴って増加傾向にあり，胃癌に次いで第2位の年間約9万人が罹患し，肺癌，胃癌に次いで第3位の約4万人が死亡している(出典：国立がんセンターがん対策情報センター)．しかし，一般的に早期発見し，内視鏡的切除や外科的切除による治療が行えれば生存率が極めて良好な癌である．そのため，早期発見のスクリーニング検査が重要である．

参考文献

1) Mandel JS, Bond JH, Church TR, et al：Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med　328：1365-1371, 1993

2) Kronborg O, Fenger C, Olsen J, et al：Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet　348：1467-1471, 1996

3) Hardcastle JD, Charmberlain JO, Robinson MH, et al：Randomised controlled trial of faecel-occult-blood screening for colorectal cancer. Lancet　348：1472-1477, 1996

4) Lieberman DA, Weiss DG, Veterans Affairs Cooperative Study Group 380：One-time screening for colorectal cancer with combined fecal occult-blood testing and examination of the distal colon. N Engl J Med　345：555-560, 2001

5) Sung JJ, Chan FK, Leung WK, et al：Screening for colorectal cancer in Chinese：comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. Gastroenterology　124：608-614, 2003

6) Imperiale TF, Ransohoff DF, Itzkowitz SH, et al：Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med　351：2704-2714, 2004

7) Morikawa T, Kato J, Yamaji Y, et al：A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population. Gastroenterology　129：422-428, 2005

8) Levi Z, Rozen P, Hazazi R, et al：A quantitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med　146：244-255, 2007

9) Lee KJ, Inoue M, Otani T, et al：Colorectal cancer screening using fecal occult blood test and subsequent risk of colorectal cancer：a prospective cohort study in Japan. Cancer Detect Prev　31：3-11, 2007

10) Groden J, Thliveris A, Samowitz W, et al：Identification and characterization of the familial adenomatous polyposis coli gene. Cell　66：589-600, 1991

11) Powell SM, Zilz N, Beazer-Barclay Y, et al：APC mutations occur early during colorectal tumorigenesis. Nature　359：235-237, 1992

12) Kinzler KW, Vogelstein B：Lessons from hereditary colorectal cancer. Cell　87：159-170, 1996

13) Miyoshi Y, Nagase H, Ando H, et al：Somatic mutations of the APC gene in colorectal tumors：mutation cluster region in the APC gene. Hum Mol Genet　1：229-233, 1992

14) Fearnhead NS, Britton MP, Bodmer WF：The ABC of APC. Hum Mol Genet 10：721-733, 2001

15) Vogelstein B, Fearon ER, Hamilton SR, et al：Genetic alterations during colorectal-tumor development. N Engl J Med　319：525-532, 1988

16) Smith AJ, Stern HS, Penner M, et al：Somatic APC and K-ras codon 12 mutations in aberrant crypt foci from human colons. Cancer Res　54：5527-5530, 1994

17) Gradfy WM, Markowitz SD：Genetic and epigenetic alterations in colon cancer. Annu Rev Genomics Hum Genet　3：101-128, 2002

18) Fearon ER, Hamilton SR, Vogelstein B：Clonal analysis of human colorectal tumors. Science　238：193-197, 1987

19) Vogelstein B, Fearon ER, Hamilton SR, et al：Genetic alterations during colorectal-tumor development. N Engl J Med　319：525-532, 1988

20) Traverso G, Shuber A, Levin B, el al：Detection of APC mutations in fecal DNA from patients with colorectal tumors. N Engl J Med　346：311-320, 2002

21) Ahlquist DA, Skoletsky JE, Boynton KA, et al：Colorectal cancer screening by detection of altered human DNA in stool：feasibility of a multitarget assay panel. Gastroenterology　119：1219-1227, 2000

22) Yamao T, Matsumura Y, Shimada Y, et al：Abnormal expression of CD44 variants in the exfoliated cells in the feces of patients with colorectal cancer. Gastroenterology　114：1196-1205, 1998

23) Matsushita H, Matsumura Y, Moriya Y, et al：A new method for isolating colonocytes from naturally evacuated feces and its clinical application to colorectal cancer diagnosis. Gastroenterology　129：1918-1927, 2005

24) Matsumura Y, Train D：Significance of CD44 gene products for cancer diagnosis and disease evaluation. Lancet　340：1053-1058, 1992

25) Matsumura Y, Hanbury D, Smith J, et al：Non-invasive detection of malignancy by identification of unusual CD44 gene activity in exfoliated cancer cells. BMJ　308：619-624, 1994