Two enemies, one fight: An update of oral cancer in patients with Fanconi anemia

Abstract

Fanconi anemia (FA) is a rare inherited genetic condition that may lead to bone marrow failure, leukemia, and/or solid tumors. It is caused by the loss of function of at least 1 gene of the FA/BRCA pathway, which is necessary for DNA repair. Patients with FA have a 200‐fold to 1000‐fold risk of developing head and neck cancer, mainly oral squamous cell carcinoma (OSCC), and of doing so at a much younger age than individuals within the general population. Also, patients who have FA with OSCC have poor overall survival rates, reinforcing the necessity to detect OSCC early. The scope of the current review is to provide an update on OSCC in patients with FA.

Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer

“…Therefore, young people who develop HNSCC must receive FA diagnostic tests. Patients with FA can present with potentially malignant disorders, especially oral leukoplakia (Amenábar et al, 2019). Among 138 Brazilian patients with FA who had not undergone hematopoietic stem cell transplantation (HSCT), 16 cases (12%) were diagnosed with oral leukoplakia, with a median age of 16.5 years (Cavalcanti et al, 2015).…”

Oral Squamous Cell Carcinoma in a Patient with Fanconi Anemia

“…It is inherited mainly via an autosomal recessive pathway [1]. The disease is characterized by progressive bone marrow failure, hyperpigmentation, pancytopenia, predisposition to both solid tumors and hematological malignancies (i.e., acute myeloid leukemia), and different kinds of congenital malformations [1][2][3]. Pathogenesis of FA involves biallelic mutations in at least one of the 23 genes responsible for chromosome stability and DNA repair via the FA/BRCA pathway [3].…”

“…As the overall outcome of HSCT has improved during the last decade, the patients with FA live longer lives. Thus, considering the cumulative risk of carcinoma development and increased survival in FA, frequency of OSCCs associated with this rare disorder can be expected to increase in the future [3][4][5].…”

“…FA leads to a 200- to 800-fold increased risk for head and neck squamous cell carcinomas. Majority of the tumors are oral squamous cell carcinomas (OSCC), and the patients are unusually young at disease presentation [ 3 ]. As the overall outcome of HSCT has improved during the last decade, the patients with FA live longer lives.…”

Fanconi Anemia: A Syndrome of Anemia and Skeletal Malformations Progressing to a Gene Network Involved in Genomic Stability and Malignant Disease

“…With the exception of the X chromosomal FANCB gene and an autosomal dominant variant in FANCR, biallelic mutations in any of these genes cause FA, and heterozygous variants in FANCD1 (BRCA2), FANCS (BRCA1), and FANCN (PALB2) result in elevated susceptibility to breast and ovarian cancer [Niraj et al, 2019]. In addition, the FANCN (PALB2; Partner and Localizer of Breast Cancer 2 [BRCA2]) gene appears to be mutated in gastric, pancreatic, and in head and neck cancer, mainly oral squamous cell carcinoma [Nepomuceno et al, 2017, Lott andCarvajal-Carmona, 2018;Amenábar et al, 2019]. Moreover, several FANC genes were previously identified in a different context (e.g., FANCG as XRCC9; FANCJ as BRIP1; FANCN as PALB2; FANCO as RAD51C; FANCP as SLX4; FANCQ as ERCC4/ XPF; FANCR as RAD51; FANCT as UBE2T; FANCU as XRCC2; FANCV as REV7/MAD2L2, and FANCW as RFWD3) [Knies et al, 2017].…”