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Parent of origin effects on age at colorectal cancer diagnosis
Author(s) -
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.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25037
Subject(s) - pseudoautosomal region , offspring , genomic imprinting , colorectal cancer , imprinting (psychology) , cancer , population , genetics , biology , gene , x chromosome , medicine , pregnancy , gene expression , dna methylation , environmental health
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.