Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A Prospective Cohort Study

Win, Aung Ko, Young, Joanne P., Lindor, Noralane M., Tucker, Katherine M., Ahnen, Dennis J., Young, Graeme P., Buchanan, Daniel D., Clendenning, Mark, Giles, Graham G., Winship, Ingrid, Macrae, Finlay A., Goldblatt, Jack, Southey, Melissa C., Arnold, Julie, Thibodeau, Stephen N., Gunawardena, Shanaka R., Bapat, Bharati, Baron, John A., Casey, Graham, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Haile, Robert W., Hopper, John L. and Jenkins, Mark A. (2012) Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A Prospective Cohort Study. Journal of Clinical Oncology, 30 9: 958-964. doi:10.1200/JCO.2011.39.5590

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ273653_OA.pdf application/pdf 131.49KB 0

Author Win, Aung Ko
Young, Joanne P.
Lindor, Noralane M.
Tucker, Katherine M.
Ahnen, Dennis J.
Young, Graeme P.
Buchanan, Daniel D.
Clendenning, Mark
Giles, Graham G.
Winship, Ingrid
Macrae, Finlay A.
Goldblatt, Jack
Southey, Melissa C.
Arnold, Julie
Thibodeau, Stephen N.
Gunawardena, Shanaka R.
Bapat, Bharati
Baron, John A.
Casey, Graham
Gallinger, Steven
Le Marchand, Loïc
Newcomb, Polly A.
Haile, Robert W.
Hopper, John L.
Jenkins, Mark A.
Title Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A Prospective Cohort Study
Journal name Journal of Clinical Oncology   Check publisher's open access policy
ISSN 0732-183X
1527-7755
Publication date 2012-03-01
Sub-type Article (original research)
DOI 10.1200/JCO.2011.39.5590
Open Access Status File (Publisher version)
Volume 30
Issue 9
Start page 958
End page 964
Total pages 7
Place of publication Alexandria, VA, United States
Publisher American Society of Clinical Oncology
Collection year 2013
Language eng
Abstract To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97). We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.
Keyword Lynch-Syndrome
Breast-Cancer
Colon-Cancer
Polymorphisms
Individuals
Onset
Hnpcc
Hmlh1
Diagnosis
Variants
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print 13 February 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 123 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 139 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 08 May 2012, 04:59:40 EST by System User on behalf of Molecular and Cellular Pathology - Sch of Med Cent