Advancements in Early Detection and Screening Strategies for Pancreatic Cancer: From Genetic Susceptibility to Novel Biomarkers
Abstract
:1. Introduction
2. Risk Factors for Pancreatic Cancer
2.1. Genetic and Familial Risk Factors
2.1.1. Peutz–Jeghers Syndrome
2.1.2. Lynch Syndrome
2.1.3. Hereditary Breast and Ovarian Cancer
2.1.4. Familial Atypical Multiple Mole Melanoma (FAMMM)
2.1.5. Li–Fraumeni Syndrome (LFS)
2.1.6. Familial Adenomatous Polyposis (FAP)
2.1.7. Ataxia–Telangiectasia Mutated (ATM)
2.1.8. Cystic Fibrosis
2.1.9. Hereditary Pancreatitis
2.2. Non-Genetic and Environmental Risk Factors
3. Age-Appropriate Screening for Pancreatic Cancer in High-Risk Groups
4. How Often Should Patients Be Screened?
5. Modalities for Screening of Pancreatic Cancer
Snapshotting Pancreatic Cancer: Exploring Early Detection with Imaging Techniques
6. Efficacy and Limitations of Current Screening Strategies for Pancreatic Cancer
6.1. Challenges in Sensitivity and Specificity
6.2. False-Positive Rates
6.3. Long-Term Outcomes
6.4. Psychological Impact
7. Promoter Methylation of ADAMTS1, BNC1, and Novel cfDNA Methylation Markers
8. Exploring Novel Biomarkers for Pancreatic Cancer Detection
9. Unlocking the Potential of Circulating Exosomes: A Promising Avenue for Pancreatic Cancer Screening
10. Advancing Pancreatic Cancer Screening: Future Directions and Recommendations
10.1. Integration of Multi-Modal Approaches
10.2. Advancements in Technology
10.3. Personalized Risk Assessment
10.4. Interdisciplinary Collaboration
10.5. Prospective Studies
11. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Genetic Syndrome | Genes Affected | Risk of Pancreatic Cancer |
---|---|---|
Peutz–Jeghers Syndrome | STK11 | Relative Risk: 132; Cumulative Risk: 2.4% at age 40, 3.9% at age 50, 11.1% at age 60, and 25.6% at age 70 years |
Lynch Syndrome | MLH1, MSH2, MSH6, PMS2 | Relative Risk: 5–9; Cumulative Risk: 1.3% by age 50 years, 3.7% by age 70 years |
Hereditary Breast and Ovarian Cancer | BRCA1, BRCA2, PALB2 | BRCA1: Relative Risk: 2.26; BRCA2: Relative Risk: 3.51 |
Familial Atypical Multiple Mole Melanoma | CDKN2A | Cumulative Risk: 17% by age 75 years |
Li–Fraumeni Syndrome | TP53 | Relative Risk: 7.73 |
Familial Adenomatous Polyposis | APC | Hazard Ratio: 6.45; Relative Risk: 4.46 |
Ataxia–Telangiectasia | ATM | Relative Risk: 6.5 |
Cystic Fibrosis | CFTR | Risk Ratio: 5.3 (95% CI: 2.4–10.1) |
Hereditary Pancreatitis | PRSS1 | Standardized Incidence Ratio: 53 (95% CI: 23–105) Cumulative Risk: 40% by age 70 years |
Risk Group | AGA Recommendation | ASGE Recommendation | CAPS Recommendation |
---|---|---|---|
Familial Pancreatic Cancer | Start screening at age 50 or 10 years younger than the initial age of onset | Start screening at age 50 or 10 years younger than the youngest relative | Start screening at age 50 or 10 years younger than the youngest relative |
Peutz–Jeghers Syndrome | Start screening at age 35 | Start screening at age 35 | Start screening at age 40 or 10 years younger than youngest relative (Grade 2: probably do it); Start screening at age 30 or 35 (Grade 4: probably do not do it) |
PRSS1 Mutation | Start screening at age 40 | Start screening at age 40 | Start screening at age 40 |
CDKN2A Mutation | Start screening at age 40 | Start screening at age 40 | Start screening at age 40 |
BRCA2 Mutation | Start screening at age 50 or 5 years earlier than high-risk individuals | Start screening at age 50 or 10 years younger than the youngest relative | Start screening at age 50 or 5 years earlier than high-risk individuals |
ATM Mutation | Start screening at age 50 | Start screening at age 50 or 10 years younger than the youngest relative | Start screening at age 50 |
PALB2 Mutation | Start screening at age 50 or 5 years earlier than high-risk individuals | Start screening at age 50 or 10 years younger than the youngest relative | Start screening at age 50 or 5 years earlier than high-risk individuals |
Lynch Syndrome | Start screening at age 50 or 10 years younger than the youngest relative | Start screening at age 50 or 10 years younger than the youngest relative | Not specified |
TP53 Mutation | Start screening at age 50 or younger depending on family history | Not specified | Not specified |
Aspect | Efficacy | Limitations |
---|---|---|
Screening Modalities | EUS and MRI are primary methods, with EUS showing high sensitivity in detecting anomalies. | Accuracy varies, and no single method is universally effective. |
Diagnostic Yield | EUS can detect 0 to 68.2 cases of pancreatic adenocarcinoma per 1000 individuals screened. | The yield for CT is lower, with 0 to 12 cases per 1000 individuals. |
Sensitivity and Specificity | High sensitivity of screening methods ensures most malignant lesions are detected. | High sensitivity may also detect benign conditions, leading to false positives. |
False-Positive Rates | - | False positives can cause psychological distress and unnecessary healthcare utilization. |
Long-Term Outcomes | Some studies suggest potential survival benefits for high-risk individuals through screening. | Conflicting results on whether screening significantly improves overall survival rates. |
Multi-Modal Approach | Description |
---|---|
Imaging Techniques | Combining CT scans, MRIs, and endoscopic ultrasound (EUS) to provide a comprehensive view of the pancreas and detect lesions. |
Biomarker Analysis | Utilizing blood tests for biomarkers like CA 19-9 alongside imaging to improve the detection of pancreatic cancer. |
Genetic Screening | Incorporating genetic testing for hereditary cancer syndromes that increase the risk of pancreatic cancer. |
Artificial Intelligence | Applying AI algorithms to analyze imaging and biomarker data for enhanced accuracy in diagnosis. |
Interdisciplinary Evaluation | A collaborative approach where gastroenterologists, oncologists, radiologists, and geneticists work together to interpret screening results. |
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Shah, Y.; Dahiya, D.S.; Tiwari, A.; Kumar, H.; Gangwani, M.K.; Ali, H.; Hayat, U.; Alsakarneh, S.; Singh, S.; Malik, S.; et al. Advancements in Early Detection and Screening Strategies for Pancreatic Cancer: From Genetic Susceptibility to Novel Biomarkers. J. Clin. Med. 2024, 13, 4706. https://doi.org/10.3390/jcm13164706
Shah Y, Dahiya DS, Tiwari A, Kumar H, Gangwani MK, Ali H, Hayat U, Alsakarneh S, Singh S, Malik S, et al. Advancements in Early Detection and Screening Strategies for Pancreatic Cancer: From Genetic Susceptibility to Novel Biomarkers. Journal of Clinical Medicine. 2024; 13(16):4706. https://doi.org/10.3390/jcm13164706
Chicago/Turabian StyleShah, Yash, Dushyant Singh Dahiya, Angad Tiwari, Harendra Kumar, Manesh Kumar Gangwani, Hassam Ali, Umar Hayat, Saqr Alsakarneh, Sahib Singh, Sheza Malik, and et al. 2024. "Advancements in Early Detection and Screening Strategies for Pancreatic Cancer: From Genetic Susceptibility to Novel Biomarkers" Journal of Clinical Medicine 13, no. 16: 4706. https://doi.org/10.3390/jcm13164706