The Association of Tumor Microsatellite Instability Phenotype with Family History of Colorectal Cancer

被引：25

作者：

Bapat, Bharati ^{[1
]}

Lindor, Noralane M. ^{[4
]}

Baron, John ^{[5
]}

Siegmund, Kim ^{[6
]}

Li, Lin ^{[7
]}

Zheng, Yingye ^{[7
]}

Haile, Robert ^{[6
]}

Gallinger, Steve ^{[2
]}

Jass, Jeremy R. ^{[8
]}

Young, Joanne P. ^{[9
]}

Cotterchio, Michelle ^{[3
]}

Jenkins, Mark ^{[10
]}

Grove, John ^{[11
]}

Casey, Graham ^{[6
]}

Thibodeau, Stephen N. ^{[4
]}

Bishop, D. Timothy ^{[12
]}

Hopper, John L. ^{[10
]}

Ahnen, Dennis ^{[13
,14
]}

Newcomb, Polly A. ^{[7
]}

Le Marchand, Loic ^{[11
]}

Potter, John D. ^{[7
]}

Seminara, Daniela ^{[15
]}

机构：

[1] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Pathol & Lab Med, Toronto, ON M5T 3L9, Canada

[2] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Surg, Toronto, ON M5T 3L9, Canada

[3] Canc Care Ontario, Toronto, ON, Canada

[4] Mayo Clin, Div Gastroenterol, Dept Med Genet, Lab Med & Pathol, Rochester, MN USA

[5] Dartmouth Med Sch, Hanover, NH USA

[6] Univ So Calif, Los Angeles, CA USA

[7] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA

[8] Univ London Imperial Coll Sci Technol & Med, Dept Pathol, London, England

[9] Royal Brisbane Hosp, Conjoint Gastroenterol Lab, Brisbane, Qld 4029, Australia

[10] Univ Melbourne, Dept Gen Practice & Publ Hlth, Melbourne, Vic 3010, Australia

[11] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA

[12] Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England

[13] Univ Colorado, Hlth Sci Ctr, Denver, CO USA

[14] Dept Vet Affairs Med Ctr, Denver, CO USA

[15] NCI, Div Canc Control & Populat Sci, Clin & Genet Epidemiol Res Branch, NIH, Bethesda, MD 20892 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2009年 / 18卷 / 03期

关键词：

COLON-CANCER; LYNCH-SYNDROME; BETHESDA GUIDELINES; LARGE BOWEL; RISK; CARCINOMA; HNPCC; FREQUENCY; RELATIVES; CRITERIA;

D O I：

10.1158/1055-9965.EPI-08-0878

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Family history is a strong predictor of colorectal cancer risk; however, a diagnosis of colorectal cancer among first-degree relatives has not been systematically investigated as a function of the colorectal cancer molecular subtypes related to tumor microsatellite instability (MSI) status. We investigated whether the observable familial colorectal cancer risks differed according to tumor MSI subtypes, stratified as MSI-High (>30% instability), MSI-Low (<30% instability), and MSS (no instability). Data from 3,143 population-based colorectal cancer cases from five institutions were assessed for family history according to the Amsterdam criteria and the Bethesda guidelines, age at diagnosis, sex, tumor location, and MST status. The distribution of patient characteristics by MST status was compared using polytomous logistic regression. Overall, 2.8% colorectal cancer cases met the Amsterdam criteria and 37% met the Bethesda guidelines. There were 14% MST-High, 13% MSI-Low, and 73% MSS colorectal cancers. MST-High (P < 0.0001) and MSI-Low tumors (P = 0.01) were more proximally located than MSS tumors. MSI-High tumors were more common among females (P < 0.001). The highest proportion of MSI-High tumors occurred in cases <40 years of age whereas the age-dependent distribution of MSI-Low tumors was unchanged. MSI-High tumors showed a statistically significant association with increasing numbers of first-degree relatives with colorectal cancer (P = 0.002); this association disappeared, however, when MSI-High cases meeting Amsterdam criteria were removed from the analysis. MSI-Low tumors did not show a similar association with family history of colorectal cancer. Familial risk associated with MSI-High tumors is primarily driven by the Amsterdam-criteria patients. MSI-Low tumors may represent a distinct subtype of colorectal cancer with respect to certain epidemiologic variables studied here. (Cancer Epidemiol Biomarkers Prev 2009;18(3): 967-75)

引用

页码：967 / 975

页数：9

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