Parent of origin effects on age at colorectal cancer diagnosis

Genomic imprinting refers to a parent‐of‐origin specific effect on gene expression. At least 1% of genes in the human genome are modulated in this manner. We sought evidence for genomic imprinting in colorectal cancer by studying the ages at diagnosis in the offspring of 2,061 parent–child pairs in...

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Veröffentlicht in:International journal of cancer 2010-07, Vol.127 (2), p.361-366
Hauptverfasser: Lindor, Noralane M., Rabe, Kari G., Petersen, Gloria M., Chen, Helen, Bapat, Bharati, Hopper, John, Young, Joanne, Jenkins, Mark, Potter, John, Newcomb, Polly, Templeton, Allyson, LeMarchand, Loic, Grove, John, Burgio, Michael R., Haile, Robert, Green, Jane, Woods, Michael O., Seminara, Daniela, Limburg, Paul J., Thibodeau, Stephen N.
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container_end_page 366
container_issue 2
container_start_page 361
container_title International journal of cancer
container_volume 127
creator Lindor, Noralane M.
Rabe, Kari G.
Petersen, Gloria M.
Chen, Helen
Bapat, Bharati
Hopper, John
Young, Joanne
Jenkins, Mark
Potter, John
Newcomb, Polly
Templeton, Allyson
LeMarchand, Loic
Grove, John
Burgio, Michael R.
Haile, Robert
Green, Jane
Woods, Michael O.
Seminara, Daniela
Limburg, Paul J.
Thibodeau, Stephen N.
description Genomic imprinting refers to a parent‐of‐origin specific effect on gene expression. At least 1% of genes in the human genome are modulated in this manner. We sought evidence for genomic imprinting in colorectal cancer by studying the ages at diagnosis in the offspring of 2,061 parent–child pairs in which both parent and child were affected by nonsyndromic colorectal cancer. Families were ascertained through the colon Cancer Family Registry [http://epi.grants.cancer.gov/CFR/] from both population‐based and clinic‐based sources. We found that the affected offspring of affected fathers were on average younger than offspring of affected mothers (55.8 vs. 53.7 years; p = 0.0003), but when divided into sons and daughters, this difference was driven entirely by younger age at diagnosis in daughters of affected fathers compared to sons (52.3 years vs. 55.1 years; p = 0.0004). A younger age at diagnosis in affected daughters of affected fathers was also observable in various subsets including families that met Amsterdam II Criteria, families that did not meet Amsterdam Criteria, and in families with documented normal DNA mismatch repair in tumors. Imprinting effects are not expected to be affected by the sex of the offspring. Possible explanations for these unexpected findings include: (i) an imprinted gene on the pseudoautosomal regions of the X chromosome; (ii) an imprinted autosomal gene that affects a sex‐specific pathway; or (iii) an X‐linked gene unmasked because of colonic tissue‐specific preferential inactivation of the maternal X chromosome.
doi_str_mv 10.1002/ijc.25037
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At least 1% of genes in the human genome are modulated in this manner. We sought evidence for genomic imprinting in colorectal cancer by studying the ages at diagnosis in the offspring of 2,061 parent–child pairs in which both parent and child were affected by nonsyndromic colorectal cancer. Families were ascertained through the colon Cancer Family Registry [http://epi.grants.cancer.gov/CFR/] from both population‐based and clinic‐based sources. We found that the affected offspring of affected fathers were on average younger than offspring of affected mothers (55.8 vs. 53.7 years; p = 0.0003), but when divided into sons and daughters, this difference was driven entirely by younger age at diagnosis in daughters of affected fathers compared to sons (52.3 years vs. 55.1 years; p = 0.0004). A younger age at diagnosis in affected daughters of affected fathers was also observable in various subsets including families that met Amsterdam II Criteria, families that did not meet Amsterdam Criteria, and in families with documented normal DNA mismatch repair in tumors. Imprinting effects are not expected to be affected by the sex of the offspring. Possible explanations for these unexpected findings include: (i) an imprinted gene on the pseudoautosomal regions of the X chromosome; (ii) an imprinted autosomal gene that affects a sex‐specific pathway; or (iii) an X‐linked gene unmasked because of colonic tissue‐specific preferential inactivation of the maternal X chromosome.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.25037</identifier><identifier>PMID: 19904757</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Age Factors ; Age of Onset ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Colorectal Neoplasms - diagnosis ; Colorectal Neoplasms - genetics ; Fathers ; Female ; Gastroenterology. Liver. Pancreas. 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A younger age at diagnosis in affected daughters of affected fathers was also observable in various subsets including families that met Amsterdam II Criteria, families that did not meet Amsterdam Criteria, and in families with documented normal DNA mismatch repair in tumors. Imprinting effects are not expected to be affected by the sex of the offspring. Possible explanations for these unexpected findings include: (i) an imprinted gene on the pseudoautosomal regions of the X chromosome; (ii) an imprinted autosomal gene that affects a sex‐specific pathway; or (iii) an X‐linked gene unmasked because of colonic tissue‐specific preferential inactivation of the maternal X chromosome.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19904757</pmid><doi>10.1002/ijc.25037</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Age Factors
Age of Onset
Aged
Aged, 80 and over
Biological and medical sciences
Colorectal Neoplasms - diagnosis
Colorectal Neoplasms - genetics
Fathers
Female
Gastroenterology. Liver. Pancreas. Abdomen
gender
Genetic Linkage
Genetic Predisposition to Disease
Genomic Imprinting - genetics
Humans
imprinting
Male
Medical sciences
Middle Aged
Mothers
pseudoautosomal
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
X‐linked
Young Adult
title Parent of origin effects on age at colorectal cancer diagnosis
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