Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome

被引：167

作者：

Win, Aung Ko ^{[1
]}

Lindor, Noralane M. ^{[3
]}

Young, Joanne P. ^{[4
,6
]}

Macrae, Finlay A.

Young, Graeme P. ^{[9
]}

Williamson, Elizabeth ^{[10
]}

Parry, Susan ^{[11
,12
]}

Goldblatt, Jack

Lipton, Lara ^{[8
]}

Winship, Ingrid ^{[2
]}

Leggett, Barbara ^{[5
,6
,13
]}

Tucker, Katherine M. ^{[14
]}

Giles, Graham G. ^{[15
]}

Buchanan, Daniel D. ^{[4
]}

Clendenning, Mark ^{[4
]}

Rosty, Christophe ^{[4
,7
]}

Arnold, Julie ^{[11
]}

Levine, A. Joan

Haile, Robert W. ^{[16
]}

Gallinger, Steven ^{[17
,18
]}

Le Marchand, Loic ^{[19
]}

Newcomb, Polly A. ^{[20
]}

Hopper, John L.

Jenkins, Mark A.

机构：

[1] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3010, Australia

[2] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia

[3] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA

[4] Queensland Inst Med Res, Canc & Populat Studies Grp, Herston, Qld 4006, Australia

[5] Queensland Inst Med Res, Conjoint Gastroenterol Lab, Pathol Queensland, Clin Res Ctr,Royal Brisbane & Womens Hosp Res Fdn, Herston, Qld 4006, Australia

[6] Univ Queensland, Sch Med, Herston, Qld, Australia

[7] Univ Queensland, Dept Mol & Cellular Pathol, Herston, Qld, Australia

[8] Royal Melbourne Hosp, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia

[9] Flinders Univ S Australia, Flinders Ctr Canc Prevent & Control, Adelaide, SA, Australia

[10] Monash Univ, Dept Epidemiol & Prevent Med, Clayton, Vic 3800, Australia

[11] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand

[12] Middlemore Hosp, Dept Gastroenterol, Auckland 6, New Zealand

[13] Royal Brisbane & Womens Hosp, Dept Gastroenterol & Hepatol, Brisbane, Qld, Australia

[14] Prince Wales Hosp, Hereditary Canc Clin, Randwick, NSW 2031, Australia

[15] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia

[16] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA

[17] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

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

[19] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA

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

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2012年 / 104卷 / 18期

基金：

美国国家卫生研究院;

关键词：

2ND PRIMARY CANCERS; SMALL-BOWEL CANCER; SUBSEQUENT PRIMARY CANCERS; MULTIPLE PRIMARY CANCERS; REPAIR GENE MUTATION; COLON-CANCER; PROSTATE-CANCER; MICROSATELLITE INSTABILITY; ENDOMETRIAL CANCER; GERMLINE MUTATIONS;

D O I：

10.1093/jnci/djs351

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers. We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The KaplanMeier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar periodspecific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population. Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97). Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.

引用

页码：1363 / 1372

页数：10

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