Hereditary cancer syndromes are genetic conditions that increase an individual's risk for multiple cancer types, often due to mutations that affect critical cellular processes such as DNA repair and cell cycle regulation. Skin cancers, including malignant melanoma (MM), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and related precancerous lesions may be underrecognized in some hereditary cancer syndromes, as suggested by underlying biological mechanisms and their underreporting in studies. In this narrative review, we examine the skin cancer risks associated with the most prevalent hereditary cancer syndromes, including Li-Fraumeni syndrome (LFS), Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), ATM-associated hereditary cancer syndrome, CHEK2-associated hereditary cancer syndrome, BRIP1-associated cancer predisposition, and hereditary leiomyomatosis and renal cell carcinoma (HLRCC). This review consolidates existing evidence and suggests that mixed cancer syndromes, especially LFS, LS, and HBOC but also pathogenic ATM and CHEK2 variants may predispose individuals to skin cancers, warranting tailored screening and preventive measures. On the basis of emerging evidence, we recommend dermatologic evaluation and individualized UV protection strategies for patients with reviewed hereditary cancer syndromes to reduce skin cancer risk and enhance early detection.

Colorectal cancer (CRC) is the third most common cancer worldwide, with 70% of cases attributed to sporadic mutations and the remaining linked to inherited genetic predispositions. This mini-review focuses on low-penetrance genetic variants that modestly influence CRC risk, categorizing them by mutation type - single nucleotide polymorphisms (SNPs) and non-SNP variants. Missense mutations in genes such as , , , and are highlighted for their varying associations with CRC risk across populations. Additionally, silent mutations, untranslated region variants, and promoter modifications, such as those in , , and , are discussed for their potential, albeit modest, roles in CRC predisposition. Non-SNP variants, including deletions and insertions in genes like , , , and , are explored for their frameshift effects and influence on CRC susceptibility. The review underscores the complexity of CRC risk, shaped by genetic, environmental, and lifestyle factors, and advocates for comprehensive, population-specific research to enhance genetic counseling and advance personalized medicine in CRC prevention and treatment.

Multiple polyposis syndromes include Familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome (PJS), Juvenile polyposis syndrome (JPS), PTEN hamartoma tumor syndrome (PHTS), MUTYH-associated polyposis (MAP), NTHL1-associated polyposis (NAP), Polymerase proofreading-associated polyposis (PPAP), and MBD4-associated polyposis. Common to these syndromes is the presence of polyps in the large intestine and very high risk of developing colorectal cancer (CRC), which can reach up to 100% in the case of FAP. The development of FAP is associated with pathogenic variants of the APC gene. However, pathogenic variants are not always detected in patients with FAP, which poses a significant clinical challenge for both patients and their families, who may be at increased risk for developing the disease. A second strong predisposition to CRC is MAP, characterized by biallelic pathogenic variants in the MUTYH gene, with a phenotype similar to FAP. This mini review focuses on potential approaches to improve the diagnosis of patients in whom pathogenic variants in the APC and MUTYH genes are not detected by routine testing.

Colorectal cancer (CRC) is the fourth most common cancer in Pakistan and poses significant public health challenges. While the majority of CRC cases are sporadic, ~ 5-10% are hereditary, linked to germline pathogenic variants (PVs) in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and other susceptibility genes (APC, EPCAM). In Pakistan, small-range PVs in MLH1 and MSH2 account for 34.5% of hereditary nonpolyposis colorectal cancer (HNPCC)/suspected-HNPCC and 1.1% of non-HNPCC cases. However, the contribution of large genomic rearrangements (LGRs) in MLH1, MSH2, MSH6, and the 3' end of EPCAM remains uncharacterized.

Neurofibromatosis type 1 (NF1; 613113) is a hereditary neurocutaneous disorder that causes tumors in the nervous system, significantly impacting the quality of life (QoL). It is characterized by diverse clinical manifestations, including café-au-lait macules (CALMs), axillary or inguinal freckling, Lisch nodules, skeletal abnormalities, and various types of neurofibromas. Plexiform neurofibromas (PN), a common complication of NF1, are often inoperable and prone to recurrence. The study aimed to describe the clinical characteristics and healthcare burden of NF1, including those with PN and those receiving Selumetinib therapy, in Saudi Arabia.

Lynch syndrome is due to error in DNA mismatch repair (MMR) genes caused by germline pathogenic variants. For some families highly suspicious of Lynch syndrome, the diagnosis may not be confirmed.

To systematically describe the genotypes and phenotypes of -associated tumour syndrome (NATS) cases reported in the literature.

Medullary breast cancer is a rare subtype of invasive breast cancer, representing from 0.2% to 6% of all breast carcinomas, with a higher proportion among women with triple-negative breast cancer and among those with a BRCA1 mutation. This review article aims to investigate the frequency of medullary breast cancer among all breast cancers and to assess its association with BRCA1 mutations. We surveyed studies involving patients diagnosed with breast cancer that report both the histology of the breast cancer as well as the presence of BRCA1 mutations. Among women with medullary breast cancer, the proportion of cases that carry a BRCA1 mutation ranges from 3% up to 35.3%, depending on the study. Among BRCA1-mutated breast cancers, the proportion that are medullary ranges from 8 to 20%. Given the notable association between medullary breast cancer and BRCA1 mutations, we propose to consider medullary breast cancer as a criterion for genetic testing in order to improve the identification of a larger number of carriers, thereby enhancing screening and prevention strategies.

Hereditary colorectal cancer (CRC) predisposition syndromes account for 5-10% of all diagnosed CRC cases. Lynch syndrome (LS), Familial Adenomatous Polyposis (FAP), and MUTYH-associated polyposis (MAP) are well-characterized hereditary syndromes known to contribute to colorectal cancer predisposition. However, other inherited genetic factors beyond these established conditions remain underexplored. Recent advancements in next-generation sequencing (NGS) have facilitated the identification of germline pathogenic variants (gPV) in cancer predisposition genes, enhancing diagnostic and management strategies for hereditary CRC syndromes. Using this technology, this study aimed to investigate the genetic causes of CRC in 23 Turkish patients belonging to 23 different families.

The genetic background of ductal carcinoma in situ (DCIS) has not been well explored. Previously, we reported that Polish founder mutations of confer susceptibility to DCIS. The aim of our study was to investigate the role of , , and mutations in the ethology of DCIS.

Methylation of has been associated with an increased risk of breast cancer and specific clinical characteristics of the disease. In the British population, the genetic alteration c.-107 A/T has been shown to cause allelic methylation, leading to familial breast and ovarian cancer. However, this variant has not been detected in Polish population. Nonetheless, other genetic variants may still be associated with methylation, highlighting the need for further research.

Cancer-related worry can significantly impact psychosocial wellbeing and decision-making, especially among individuals with hereditary cancer risk. Although the Cancer Worry Scale is a commonly used instrument, no culturally adapted version exists for German speaking populations. This study aimed to translate, culturally adapt and pilot-test a German version of the 8-item Cancer Worry Scale in individuals carrying BRCA1 or BRCA2 pathogenic variants in Austria.

The role of genetics in breast cancer management is becoming increasingly essential in sub-Saharan Africa (SSA). Harmonized Guidelines by the National Comprehensive Cancer Network (NCCN) for SSA outline the subset of patients requiring genetic testing for hereditary breast cancer as part of their treatment plan. However, in low-and middle-income countries (LMICs) like Nigeria, access to genetic counselling and testing remains limited. Additionally, the knowledge and acceptability of these available services from the healthcare provider (HCP) perspective are largely unknown. This study aimed to assess the knowledge and perceptions of hereditary breast cancer testing among HCPs in Nigeria.

While numerous studies have demonstrated variations in colorectal cancer (CRC) incidence among Lynch Syndrome (LS)-associated germline pathogenic variant (gPV) carriers, limited data are available regarding tailoring surveillance and treatment strategies. The main goal of this study was to estimate whether personalised care could be offered based on the different gPVs (MLH1, MSH2, MSH6 or PMS2). Additionally, the outcome from patient-shared care for early (T1) CRC was investigated.

While enhanced breast screening of germline pathogenic variant (GPV) carriers results in earlier stage at diagnosis, the impact of tumour biology and GPV on chemotherapy receipt in early-stage disease remains understudied.

Pathogenic variants in BRCA1 and BRCA2 are associated with an increased risk of developing several types of cancer, including breast cancer. However, the risk varies by other environmental and genetic factors present in carriers of mutation. To understand the value of these factors more clearly, a number of common genetic susceptibility variants have been studied through genome-wide association studies as potential genetic risk modifiers for BRCA1 and BRCA2 pathogenic variants carriers. Several studies have identified specific polymorphisms that may influence the risk of breast cancer development, either by increasing or reducing susceptibility. These variants are implicated in biological pathways such as DNA damage repair, hormonal regulation or cell proliferation. The identification and understanding of key genetic modifiers may provide valuable insights into development of personalized prevention, targeted therapies and screening strategies for high-risk individuals. This review presents the overview of known genetic risk modifiers for carriers of BRCA1 and BRCA2 pathogenic variants, their potential impact on risk, and their functional roles. Furthermore, it highlights the need for further research directions, including understanding the biological role of genetic modifiers in cancer development and the refinement of risk assessment models.

Prostate Cancer (PrCa) is one of the most common cancers worldwide and causes a significant healthcare burden. Recent predictions estimate the incidence of new cases of PrCa will double from 1.4 million in 2020 to 2.9 million by 2040.The known risk factors for PrCa are increasing age, family history, ancestry and genetics. PrCa is one of the most heritable of the more common cancers. The heritability of PrCa is due to both rare moderate to high-risk monogenic variants and more common variants known as single nucleotide polymorphisms (SNPs) which can be used to calculate a polygenic risk score (PRS) for PrCa, while there is some of the genetic risk as yet unexplained. In recent years more PrCa risk-associated SNPs have been identified, increasing over time with the inclusion of more persons of diverse ancestry in studies. The identification of germline variants known to be associated with increased PrCa risk and disease aggressiveness has led to targeted treatments for certain pathogenic variant carriers.This is a mini review of how the genetics of PrCa can impact on screening and early detection of the disease and the treatment and management of the disease when diagnosed.

Breast cancer (BC) is the most common malignancy among Iranian females, accounting for 24.4% of all malignancies. Germ line mutations in DNA repair system-related genes are associated with an increased risk of BC. This study aims to evaluate the frequencies of single nucleotide polymorphisms (SNPs) in the BRCA1, BRCA2, and PALB2 genes in patients with BC from a subset of the Iranian population in the western part of Iran.

The Swedish Family-Cancer Database (FCD) is the largest source of data on familial cancer in the world, including practically complete family structures and individual cancer diagnoses from the high-quality cancer registry. We present a novel application of FCD by analyzing age-specific familial risks and interpreting them through likely causes, such as germline pathogenic variants and/or environmental exposures.

Germline genetic susceptibilities of rare cancers of the esophagus, stomach, small intestine, testis, (nonmedullary) thyroid gland and bone with high familial risks are not well known. Here, we use familial risk data from the Swedish Family-Cancer Database which contains records of cancers in Swedish families obtained over a century. We compare familial risks for offspring diagnosed with any of these cancers when their parent had or had not that cancer. We review the global literature of the reported constitutional variants that may explain part of the familial risk.

There is an increasing recognition that comprehensive tumour profiling (CTP) represents an important adjunct to the diagnosis of malignancy providing not only an assessment of how many mutations there are in any given tumour which reflects the probability of immune checkpoint inhibitor success, but also which mutations are associated with targeted therapies, a signature that reflects environmental insult and potentially the identification of cancers of unknown origin.This short review describes an approach to assaying tumour mutational burden (TMB), what the difficulties are in the assessment of the TMB and what it can be applied to in regards to improving patient outcomes. A final section of the review delves into some examples of colorectal cancer studies that identify findings that suggest there remains much to learn about tumour development.