Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans.
Cancer Lett
; 380(2): 442-446, 2016 10 01.
Article
in En
| MEDLINE
| ID: mdl-27424524
ABSTRACT
Non-specific chromosomal aberrations (CAs) are microscopically detected in about 1% of lymphocytes drawn from healthy persons. Causes of CAs in general population are not known but they may be related to risk of cancer. In view of the importance of the mitotic checkpoint machinery on maintaining chromosomal integrity we selected 9 variants in main checkpoint related genes (BUB1B, BUB3, MAD2L1, CENPF, ESPL1/separase, NEK2, PTTG1/securin, ZWILCH and ZWINT) for a genotyping study on samples from healthy individuals (N = 330 to 729) whose lymphocytes had an increased number of CAs compared to persons with a low number of CAs. Genetic variation in individual genes played a minor importance, consistent with the high conservation and selection pressure of the checkpoint system. However, gene pairs were significantly associated with CAs PTTG1-ZWILCH and PTTG1-ZWINT. MAD2L1 and PTTG1 were the most common partners in any of the two-way interactions. The results suggest that interactions at the level of cohesin (PTTG1) and kinetochore function (ZWINT, ZWILCH and MAD2L1) contribute to the frequency of CAs, suggesting that gene variants at different checkpoint functions appeared to be required for the formation of CAs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Variation
/
Lymphocytes
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Chromosome Aberrations
/
Genes, cdc
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Cell Cycle Proteins
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M Phase Cell Cycle Checkpoints
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Cancer Lett
Year:
2016
Document type:
Article