TY - JOUR
T1 - Multi-locus inherited neoplasia alleles syndromes in cancer
T2 - implications for clinical practice
AU - Yuen, Jeanette
AU - Zhou, Siqin
AU - Caeser, Rebecca
AU - Venkatramani, Mallika
AU - Bte Ishak, Diana Nur
AU - Li, Shao Tzu
AU - Zhang, Zewen
AU - Chiang, Jianbang
AU - Chan, Sock Hoai
AU - Ngeow, Joanne
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025
Y1 - 2025
N2 - The popularity of multi-gene testing has identified more families with two or more pathogenic variants (PV) in cancer predisposition genes, also known as ‘MINAS’ (multilocus inherited neoplasia alleles syndromes). They are at risk of suboptimal treatment and management as little on this topic is known. We conducted a systematic review of published MINAS cases within cancer predisposition genes to understand their association with more severe presentations. We analysed 413 MINAS carriers, which included 33 novel cases from the Cancer Genetics Service, National Cancer Centre Singapore. Statistical tests were conducted to assess association between carrier characteristics and the number PV identified. Results suggest that MINAS carriers have more malignancies (31.7% vs 21.5% vs 10.3% %; p < 0.001), a younger median age of first cancer diagnosis (40.0 vs. 44.0 vs. 49.0 years; p < 0.001) and an early onset of cancer (defined as <5% PV-associated cancer risk at age of diagnosis) (24.9% vs 7.7% vs 4.7%; p < 0.001) compared to monoallelic and non-carriers. We also studied the association of clinical characteristics by the dominant or recessive nature of PV harboured, where more dominant-dominant (D-D) carriers reported multiple malignancies (34.0%), compared to dominant-recessive (D-R) (23.9%) and recessive-recessive (R-R) carriers (20%;) (p = 0.051). Our findings suggest that MINAS carriers are prone to more and younger malignancies and the dominant or recessive nature of PV within double carriers can affect clinical presentation. We suggest a framework to guide management based on the dominant or recessive nature of PV within double PV carriers.
AB - The popularity of multi-gene testing has identified more families with two or more pathogenic variants (PV) in cancer predisposition genes, also known as ‘MINAS’ (multilocus inherited neoplasia alleles syndromes). They are at risk of suboptimal treatment and management as little on this topic is known. We conducted a systematic review of published MINAS cases within cancer predisposition genes to understand their association with more severe presentations. We analysed 413 MINAS carriers, which included 33 novel cases from the Cancer Genetics Service, National Cancer Centre Singapore. Statistical tests were conducted to assess association between carrier characteristics and the number PV identified. Results suggest that MINAS carriers have more malignancies (31.7% vs 21.5% vs 10.3% %; p < 0.001), a younger median age of first cancer diagnosis (40.0 vs. 44.0 vs. 49.0 years; p < 0.001) and an early onset of cancer (defined as <5% PV-associated cancer risk at age of diagnosis) (24.9% vs 7.7% vs 4.7%; p < 0.001) compared to monoallelic and non-carriers. We also studied the association of clinical characteristics by the dominant or recessive nature of PV harboured, where more dominant-dominant (D-D) carriers reported multiple malignancies (34.0%), compared to dominant-recessive (D-R) (23.9%) and recessive-recessive (R-R) carriers (20%;) (p = 0.051). Our findings suggest that MINAS carriers are prone to more and younger malignancies and the dominant or recessive nature of PV within double carriers can affect clinical presentation. We suggest a framework to guide management based on the dominant or recessive nature of PV within double PV carriers.
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U2 - 10.1038/s41431-025-01785-1
DO - 10.1038/s41431-025-01785-1
M3 - Article
C2 - 39843919
AN - SCOPUS:85217225338
SN - 1018-4813
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
M1 - 15
ER -