Prevalence and Penetrance of Major Genes and Polygenes for Colorectal
Cancer

Win, Aung Ko; Jenkins, Mark A.; Dowty, James G.; Antoniou, Antonis C.; Lee, Andrew; Giles, Graham G.; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Ahnen, Dennis J.; Thibodeau, Stephen N.; Casey, Graham; Gallinger, Steven; Le Marchand, Loïc; Haile, Robert W.; Potter, John D.; Zheng, Yingye; Lindor, Noralane M.; Newcomb, Polly A.; Hopper, John L.; MacInnis, Robert J.

Back to Previous Page

- Add this to...
- Twitter
- Facebook
- Google Bookmarks
- LinkedIn

Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer

Published Date:

Oct 31 2016

Source:

Cancer Epidemiol Biomarkers Prev. 26(3):404-412.

[PDF-398.65 KB]

Details:

Personal Authors:

Win, Aung Ko ; Jenkins, Mark A. ; Dowty, James G. ; Antoniou, Antonis C. ; Lee, Andrew ; ... More ▼

Keywords:

[+]

Pubmed ID:

27799157

Pubmed Central ID:

PMC5336409

Description:

Background

While high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known.

Methods

We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the USA, Canada and Australia and screened probands for mutations in mismatch repair genes and MUTYH. We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband’s age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of and hazard ratio for unidentified major gene mutations, and the variance of the residual polygenic component.

Results

We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1= 1 in 1946, MSH2= 1 in 2841, MSH6= 1 in 758, PMS2= 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30–50% after allowing for unidentified major genes and decreased from 3.3 for age <40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).

Conclusion

Unidentified major genes might explain one-third to one-half of the missing heritability of colorectal cancer.

Impact

Our findings could aid gene discovery and development of better colorectal cancer risk prediction models.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

Supporting Files:

	NIHMS827219-supplement-1.docx	application/vnd.openxmlformats-officedocument.wordprocessingml.document
	NIHMS827219-supplement-2.docx	application/vnd.openxmlformats-officedocument.wordprocessingml.document
	nihms827219.nxml	text/xml
	nihms827219f1.gif	image/gif
	nihms827219f1.jpg	image/jpeg

No Related Documents.

You May Also Like:

How can polygenic inheritance be used in population screening for common diseases?

Personal Author:

Khoury, Muin J.; Janssens, A. Cecile J.W.; Ransohoff, David F.;

Published:

Feb 14 2013

Source:

Genet Med. 15(6):437-443.

Description:

Advances in genomics have near-term impact on diagnosis and management of monogenic disorders. For common complex diseases, the use of genomic information from multiple loci (polygenic model) is generally not useful for diagnosis and individual predi...

File Type:

[PDF - 96.37 KB]
Clinical penetrance in hereditary hemochromatosis: estimates of the cumulative incidence of severe liver disease among HFE C282Y homozygotes

Personal Author:

Grosse, Scott D.; Gurrin, Lyle C.; Bertalli, Nadine A.; Allen, Katrina J.;

Published:

August 03 2017

Source:

Genet Med. 20(4):383-389

Description:

Iron overload (hemochromatosis) can cause serious, symptomatic disease that is preventable if detected early and managed appropriately. The leading cause of hemochromatosis in populations of predominantly European ancestry is homozygosity of the C282...

File Type:

[PDF - 75.82 KB]
Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH

Personal Author:

Win, Aung Ko; Reece, Jeanette C.; Dowty, James G.; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Southey, Melissa C.; Young, Joanne P.; Cleary, Sean P.; Kim, Hyeja; Cotterchio, Michelle; Macrae, Finlay A.; Tucker, Katherine M.; Baron, John A.; Burnett, Terrilea; Le Marchand, Loïc; Casey, Graham; Haile, Robert W.; Newcomb, Polly A.; Thibodeau, Stephen N.; Hopper, John L.; Gallinger, Steven; Winship, Ingrid M.; Lindor, Noralane M.; Jenkins, Mark A.;

Published:

Jun 02 2016

Source:

Int J Cancer. 139(7):1557-1563.

Description:

Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands...

File Type:

[PDF - 235.11 KB]
Can targeted genetic testing offer useful health information to adoptees?

Personal Author:

May, Thomas; Strong, Kimberly A.; Khoury, Muin J.; Evans, James P.;

Published:

Apr 23 2015

Source:

Genet Med. 17(7):533-535.

File Type:

[PDF - 50.01 KB]
Genomics and population health; United States 2003

Personal Author:

Gwinn, Marta

Corporate Author:

Centers for Disease Control and Prevention (U.S.), Office of Genomics and Disease Prevention.

Published:

March 2004

Description:

Foreword -- Genomics and Population Health, 2003: Year at a Glance -- Genomics Lingo⁵..What Do the Terms Mean? -- List of Authors -- -- I. Population Health Research -- Chapter 1. National Health and Nutrition Examination Survey (NHANES) III DNA Ba...

File Type:

[PDF - 9.08 MB]