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Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition
Author(s) -
Cavaillé Mathias,
Uhrhammer Nancy,
Privat Maud,
PonelleChachuat Flora,
GayBellile Mathilde,
Lepage Mathis,
Molnar Ioana,
Viala Sandrine,
Bidet Yannick,
Big YvesJean
Publication year - 2021
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22911
Subject(s) - genetics , genetic predisposition , cancer , ovarian cancer , candidate gene , medicine , colorectal cancer , genetic testing , mutation , breast cancer , biology , gene
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.