# From Genomics to AI: Revolutionizing Precision Medicine in Oncology
## 3 Genomics in Cancer Risk Assessment
Germline heterozygous variants in the mismatch repair genes predispose individuals to [PERSON] syndrome, and, in rare cases, genomic deletions at the 3\({}^{\prime}\) end of EPCAM can lead to epigenetic silencing of MSH2, further contributing to genetic predisposition [30]. Early detection through genetic testing allows for tailored surveillance programs and preventive measures to reduce cancer risk in individuals with [PERSON] syndrome, such as prophylactic surgeries [31]. Other examples of hereditary cancer syndromes are hereditary retinoblastoma, caused by pathogenic variants in the _RB1_ gene, which follows [PERSON]'s two-hit hypothesis [32]. High-penetrance genes, such as _TP53_, associated with Li-Fraumeni Syndrome, and _APC_, responsible for Familial Adenomatous Polyposis, also require specific surveillance strategies [33; 34]. A summary of key genes associated with hereditary cancer syndromes, their related malignancies, and clinical management approaches is provided in Table 2.  
The advent of NGS has expanded the capacity to identify novel cancer susceptibility genes and rare variants with significant clinical impact. Germline testing for these variants has increasingly been integrated into oncology care, particularly in cases of early onset or multiple primary tumors. These insights have not only improved clinical outcomes but also support informed reproductive decisions, with preimplantation genetic diagnosis (PGD) now available for families with known hereditary cancer syndromes [40]. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Gene** & **Syndrome** & **Associated Cancers** & **Risk Management/Notes** & **References** \\ \hline \multirow{4}{*}{_BRCA1/BRCA2_} & Hereditary Breast and & Breast, ovarian, & Enhanced surveillance, & \\  & Ovarian Cancer & prostate, pancreatic & chemopre, & \\  & (HBOC) & & risk-reducing surgery & \\  & & Colorectal, & risk-reducing surgery & \\  & _MLH1_, _MSH2_, _MSH6_, & & & \\  & Lynch Syndrome & endometrial, ovarian, & Colonoscopic surveillance, & \\  & & gastric, small & prophylactic surgery & \\  & & intestine & & \\  & Hereditary & Retinoblastoma, & Regular ophthalmologic & \\  & Retinoblastoma & sarcoma, melanoma & exams, risk of secondary & \\  & & Breast, sarcomas, & tumors & \\  & Li–Fraumeni & brain tumors, & Whole-body MRI, early & \\  & Syndrome (LFS) &adrenocortical & cancer screening & \\  & & carcinoma & & \\  & Familial Adenomatous & Colorectal, duodenal & Colonoscopy, & \\  & Polyposis (FAP) & & prophylactic osteotomy & \\  & & Breast, thyroid, & Early screening, & \\  & & endometrial & risk-reducing surgery & \\  & & Familial Melanoma & Melanoma, & Dermatologic screening, & \\  & Syndrome & pancreatic & pancreatic imaging & \\  & Von Hippel–Lindau & Renal cell carcinoma, & Renal imaging, CNS & \\  & Syndrome & hemangioblastoma & surveillance & \\  & Multiple Endocrine & Medullary thyroid & Prophylactic & \\  & Neoplasia Type 2 & carcinoma, & thyroidectomy, & [39] \\  & & pheochromocytoma & biochemical monitoring & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Overview of major genes involved in hereditary cancer syndromes. The table outlines the associated cancer types and typical risk management strategies, including surveillance and preventive interventions. With the continuous progression of genomic technologies and their integration into clinical practice, genetic counseling will remain a cornerstone of personalized cancer risk management. The ability to combine germline testing, somatic tumor profiling, and polygenic risk scores into a unified cancer risk assessment framework will allow oncologists and genetic counselors to provide more personalized recommendations, ultimately improving patient outcomes and reducing the impact of hereditary cancer. Beyond single-gene variants, genomics has also fostered the use of polygenic risk scores (PRSs), which assess an individual's risk of developing cancer based on the cumulative effect of multiple genetic variants.