Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition.
Genes Chromosomes Cancer
; 60(2): 73-78, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-33099839
ABSTRACT
Hereditary predisposition to cancer concerns between 5% and 10% of cancers. The main genes involved in the most frequent syndromes (hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome) were identified in the 1990s. Exploration of their functional pathways then identified novel genes for hereditary predisposition to cancer, and candidate genes whose involvement remains unclear. To determine the contribution of truncating variants in 11 candidate genes (BARD1, FAM175A, FANCM, MLH3, MRE11A, PMS1, RAD50, RAD51, RAD51B, RINT1, and XRCC2) to cancer predisposition in a population of interest, panel sequencing was performed in 849 patients with a suspected hereditary predisposition to cancer for whom a diagnostic panel of 38 genes identified no causal mutation. Sixteen truncating variants were found in FANCM (n = 7), RINT1 (n = 4), RAD50 (n = 2), BARD1, PMS1, and RAD51B. FANCM (adjusted P-value .03) and RINT1 (adjusted P-value .04) were significantly associated with hereditary breast and ovarian cancer. However, further studies are required to determinate the risk of cancer, including the segregation of the variants in the families of our cases. No mutation was identified in RAD51, MRE11A, FAM175A, XRCC2, or MLH3. The involvement of these genes in the hereditary predisposition to cancer cannot be ruled out, although if it exists it is rare or does not seem to involve truncating variants.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms, Hereditary Nonpolyposis
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Genetic Predisposition to Disease
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Genetic Loci
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Hereditary Breast and Ovarian Cancer Syndrome
Limits:
Female
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Humans
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Male
Language:
En
Journal:
Genes Chromosomes Cancer
Journal subject:
BIOLOGIA MOLECULAR
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NEOPLASIAS
Year:
2021
Document type:
Article
Affiliation country:
France
Publication country:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA