Parent of origin effects on age at colorectal cancer diagnosis

Noralane Morey Lindor, Kari G. Rabe, Gloria M Petersen, Helen Chen, Bharati Bapat, John Hopper, Joanne Young, Mark Jenkins, John Potter, Polly Newcomb, Allyson Templeton, Loic LeMarchand, John Grove, Michael R. Burgio, Robert Haile, Jane Green, Michael O. Woods, Daniela Seminara, Paul John Limburg, Stephen N Thibodeau

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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/ 〈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.

Original languageEnglish (US)
Pages (from-to)361-366
Number of pages6
JournalInternational Journal of Cancer
Volume127
Issue number2
DOIs
StatePublished - Jul 15 2010

Fingerprint

Nuclear Family
Colorectal Neoplasms
Fathers
Genomic Imprinting
Organized Financing
Mothers
Genes
X Chromosome Inactivation
Neoplasms
X-Linked Genes
DNA Mismatch Repair
X Chromosome
Human Genome
Colonic Neoplasms
Registries
Gene Expression
Population

Keywords

  • Gender
  • Imprinting
  • Pseudoautosomal
  • X-linked

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Parent of origin effects on age at colorectal cancer diagnosis. / Lindor, Noralane Morey; 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 John; Thibodeau, Stephen N.

In: International Journal of Cancer, Vol. 127, No. 2, 15.07.2010, p. 361-366.

Research output: Contribution to journalArticle

Lindor, NM, Rabe, KG, Petersen, GM, Chen, H, Bapat, B, Hopper, J, Young, J, Jenkins, M, Potter, J, Newcomb, P, Templeton, A, LeMarchand, L, Grove, J, Burgio, MR, Haile, R, Green, J, Woods, MO, Seminara, D, Limburg, PJ & Thibodeau, SN 2010, 'Parent of origin effects on age at colorectal cancer diagnosis', International Journal of Cancer, vol. 127, no. 2, pp. 361-366. https://doi.org/10.1002/ijc.25037
Lindor, Noralane Morey ; 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 John ; Thibodeau, Stephen N. / Parent of origin effects on age at colorectal cancer diagnosis. In: International Journal of Cancer. 2010 ; Vol. 127, No. 2. pp. 361-366.
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