Cumulative Incidence of Colorectal and Extracolonic Cancers in MLH1 and MSH2 Mutation Carriers of Hereditary Nonpolyposis Colorectal Cancer

被引：97

作者：

Lin K.M. ^{[1
]}

Shashidharan M. ^{[1
]}

Thorson A.G. ^{[1
,3
]}

Ternent C.A. ^{[1
]}

Blatchford G.J. ^{[1
]}

Christensen M.A. ^{[1
]}

Watson P. ^{[2
]}

Lemon S.J. ^{[2
]}

Franklin B. ^{[2
]}

Karr B. ^{[2
]}

Lynch J. ^{[2
]}

Lynch H.T. ^{[2
]}

机构：

[1] Section of Colon and Rectal Surgery, Department of Surgery, Creighton Univ. School of Medicine, Omaha, NE

[2] Dept. of Prev. Med. and Pub. Health, Hereditary Cancer Institute, Creighton University, Omaha, NE

[3] Creighton University Medical Center, Section of Colon and Rectal Surgery, Omaha, NE 68131-2197, 601 N. 30th St.

来源：

Journal of Gastrointestinal Surgery | 1998年 / 2卷 / 1期

关键词：

Endometrial Cancer; Cumulative Incidence; Lynch Syndrome; Hereditary Nonpolyposis Colorectal Cancer; Colorectal Cancer Risk;

D O I：

10.1016/S1091-255X(98)80105-4

中图分类号：

学科分类号：

摘要：

The extracolonic tumor spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) includes cancer of the endometrium, ovaries, stomach, biliary tract, and urinary tract. This study was designed to determine the penetrance of colorectal and extracolonic tumors in HNPCC mutation carriers. Forty-nine patients (22 females and 27 males) were identified with an MSH2 germline mutation, and 56 patients (28 females and 28 males) were identified with an MLH1 mutation. Cumulative incidence by age 60 (lifetime risk) and mean age of cancer diagnosis were compared. The lifetime risk of extracolonic cancers in MSH2 and MLH1 carriers was 48% and 11% respectively (P = 0.016). Extracolonic cancer risk in MSH2 females and males was 69% and 34%, respectively (P = 0.042). Mean age of extracolonic cancer diagnosis was significantly older for MSH2 males than females (55.4 vs. 39.0, P = 0.013). No difference was observed in colorectal cancer risk between MLH1 and MSH2 carriers (84% vs. 71%). Colorectal cancer risk was 96% in MSH2 males compared to 39% in MSH2 females (P = 0.034). No differences in colorectal and extracolonic cancer risks between MLH1 females and males were identified. The risk of extracolonic cancer by age 60 was greater in MSH2 mutation carriers than in MLH1 carriers. Gender differences in colorectal and extracolonic cancer risk were observed for MSH2 carriers only. These phenotypic features of HNPCC genotypes may have clinical significance in the design of genotype-specific screening, surveillance, and follow-up for affected individuals.

引用

页码：67 / 71

页数：4

共 31 条

[1]

Winawer S.J., Fletcher R.H., Miller R., Et al., Colorectal cancer screening: Clinical guidelines and rationale, Gastroenterology, 112, pp. 594-642, (1997)

[2]

Bellacosa A., Genuardi M., Anti M., Viel A., Ponz De Leon M., Hereditary nonpolyposis colorectal cancer: Review of clinical, molecular genetics, and counseling aspects, Am J Med Genet, 62, pp. 353-364, (1996)

[3]

Marra G., Boland C.R., Hereditary nonpolyposis colorectal cancer: The syndrome, the genes, and historical perspectives, J Natl Cancer Inst, 87, pp. 1114-1125, (1995)

[4]

Mecklin J.P., Jarvinen H.J., Hakkiluoto A., Et al., Frequency of hereditary nonpolyposis colorectal cancer. A prospective multicenter study in Finland, Dis Colon Rectum, 38, pp. 588-593, (1995)

[5]

Lynch H.T., Smyrk T., Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review, Cancer, 78, pp. 1149-1167, (1996)

[6]

Tomoda H., Baba H., Oshiro T., Clinical manifestations in patients with hereditary nonpolyposis colorectal cancer, J Surg Oncol, 61, pp. 262-266, (1996)

[7]

D'Emilia J.C., Rodriguez-Bigas M.A., Petrelli N.J., The clinical and genetic manifestations of hereditary nonpolyposis colorectal carcinoma, Am J Surg, 169, pp. 368-372, (1995)

[8]

Percesepe A., Anti M., Marra G., Et al., Role of clinical criteria in the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC): Results of a multivariate analysis, Int J Cancer, 58, pp. 799-802, (1994)

[9]

Lynch H.T., Smyrk T.C., Cavalieri J., Lynch J.F., Identification of an HNPCC family, Am J Gastroenterol, 89, pp. 605-609, (1994)

[10]

Whitehouse A., Taylor G.R., Deeble J., Et al., A carboxy terminal domain of the hMSH-2 gene product is sufficient for binding specific mismatched oligonucleotides, Biochem Biophys Res Commun, 225, pp. 289-295, (1996)

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