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Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer
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| Zeitschriftentitel: | Cancer Epidemiology, Biomarkers & Prevention |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , |
| In: | Cancer Epidemiology, Biomarkers & Prevention, 26, 2017, 3, S. 404-412 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
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. 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. |
|---|---|
| author |
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. |
| spellingShingle |
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. Cancer Epidemiology, Biomarkers & Prevention Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer Oncology Epidemiology |
| author_sort |
win, aung ko |
| spelling |
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. 1055-9965 1538-7755 American Association for Cancer Research (AACR) Oncology Epidemiology http://dx.doi.org/10.1158/1055-9965.epi-16-0693 <jats:title>Abstract</jats:title> <jats:p>Background: Although 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.</jats:p> <jats:p>Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, 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 HR for unidentified major gene mutations, and the variance of the residual polygenic component.</jats:p> <jats:p>Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, 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% to 50% after allowing for unidentified major genes and decreased from 3.3 for age &lt;40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).</jats:p> <jats:p>Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer.</jats:p> <jats:p>Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404–12. ©2016 AACR.</jats:p> Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer Cancer Epidemiology, Biomarkers & Prevention |
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10.1158/1055-9965.epi-16-0693 |
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American Association for Cancer Research (AACR), 2017 |
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American Association for Cancer Research (AACR), 2017 |
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Cancer Epidemiology, Biomarkers & Prevention |
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| title |
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_unstemmed |
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_full |
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_fullStr |
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_full_unstemmed |
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_short |
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_sort |
prevalence and penetrance of major genes and polygenes for colorectal cancer |
| topic |
Oncology Epidemiology |
| url |
http://dx.doi.org/10.1158/1055-9965.epi-16-0693 |
| publishDate |
2017 |
| physical |
404-412 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Background: Although 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.</jats:p>
<jats:p>Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, 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 HR for unidentified major gene mutations, and the variance of the residual polygenic component.</jats:p>
<jats:p>Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, 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% to 50% after allowing for unidentified major genes and decreased from 3.3 for age &lt;40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).</jats:p>
<jats:p>Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer.</jats:p>
<jats:p>Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404–12. ©2016 AACR.</jats:p> |
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| author | 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. |
| author_facet | 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., 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. |
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| description | <jats:title>Abstract</jats:title> <jats:p>Background: Although 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.</jats:p> <jats:p>Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, 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 HR for unidentified major gene mutations, and the variance of the residual polygenic component.</jats:p> <jats:p>Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, 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% to 50% after allowing for unidentified major genes and decreased from 3.3 for age &lt;40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).</jats:p> <jats:p>Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer.</jats:p> <jats:p>Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404–12. ©2016 AACR.</jats:p> |
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| imprint_str_mv | American Association for Cancer Research (AACR), 2017 |
| institution | DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4 |
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| spelling | 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. 1055-9965 1538-7755 American Association for Cancer Research (AACR) Oncology Epidemiology http://dx.doi.org/10.1158/1055-9965.epi-16-0693 <jats:title>Abstract</jats:title> <jats:p>Background: Although 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.</jats:p> <jats:p>Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, 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 HR for unidentified major gene mutations, and the variance of the residual polygenic component.</jats:p> <jats:p>Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, 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% to 50% after allowing for unidentified major genes and decreased from 3.3 for age &lt;40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).</jats:p> <jats:p>Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer.</jats:p> <jats:p>Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404–12. ©2016 AACR.</jats:p> Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer Cancer Epidemiology, Biomarkers & Prevention |
| spellingShingle | 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., Cancer Epidemiology, Biomarkers & Prevention, Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer, Oncology, Epidemiology |
| title | Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_full | Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_fullStr | Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_full_unstemmed | Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_short | Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| title_sort | prevalence and penetrance of major genes and polygenes for colorectal cancer |
| title_unstemmed | Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer |
| topic | Oncology, Epidemiology |
| url | http://dx.doi.org/10.1158/1055-9965.epi-16-0693 |