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©2011 Baishideng Publishing Group Co.
World J Gastroenterol. Jun 28, 2011; 17(24): 2897-2908
Published online Jun 28, 2011. doi: 10.3748/wjg.v17.i24.2897
Published online Jun 28, 2011. doi: 10.3748/wjg.v17.i24.2897
Table 1 Pancreatic cancer risk factors
Factor | Type | Group | Maximum risk to average ratio |
Smoking | Exogenous | Behavioral | 3 |
Alcohol | Exogenous | Behavioral | Non-significant |
Diet/obesity | Exogenous | Behavioral | 1.72 |
Occupational hazard | Exogenous | Environmental | - |
Radiation | Exogenous | Environmental | Inconclusive |
Age | Endogenous | Biological | - |
Race | Endogenous | Biological/behavioral/environmental | 1.4 |
Family history | Endogenous | Genetic | 32 |
Peutz-Jeghers syndrome | Endogenous | Genetic | 132 |
FAMMM syndrome | Endogenous | Genetic | 13.1 |
HNPCC | Endogenous | Genetic | 7 |
Hereditary pancreatitis | Endogenous | Genetic | 60 |
Chronic pancreatitis | Endogenous | Behavioral | 26.3 |
Diabetes mellitus | Endogenous | Biological/environmental | 2.0 |
Hormonal | Endogenous | Biological | Inconclusive |
Allergy | Endogenous | Biological | Non-significant |
Gene symbols | Protein name | Mutation frequency (%) | Type | Main signaling or system |
KRAS | K-ras | 58 | Proto-oncogene | Ras/Raf/MAPK |
TP53 | Tumor protein p53 | 37 | Tumor suppressor | Apoptosis Cell cycle control |
CDKN2A | Tumor protein p16 (INK4A) | 29 | Tumor suppressor | Cell cycle control |
CTNNB1 | β-catenin | 24 | Proto-oncogene | Wnt |
SMAD4 DPC4 | Smad Dpc4 | 22 | Tumor suppressor | TNFbeta/SMAD |
APC | Apc | 16 | Tumor suppressor | Wnt |
PIK3CA | Phosphoinositide 3-kinase | 5 | Proto-oncogene | PTEN/PI3K/AKT |
Table 3 Overview of hereditary syndromes predisposing to pancreatic cancer
Syndrome | Gene | Life-time risk | Relative risk |
FAMMM | CDKN2A | 10%-15% | 20-34 |
HBOC | BRCA2 | 5% | 10 |
HBOC | BRCA1 | Not known | 2 |
Hereditary pancreatitis | PRSS1/TRY1 | 30%-50% | 50 |
Lynch syndrome | MLH1/MSH2 | Not known | Not known |
Peutz–Jeghers syndrome | STK11/LKB1 | 36% | 136 |
FAP | APC | Not known | 4 |
Li–Faumeni syndrome | p53 | Not known | Not known |
FPC | Not known | Up to 50% | 18-57 |
Table 4 Overview of biomarkers in pancreatic cancer
Biomarker | Sensitivity (%) | Specificity (%) |
CEA | 45 | 75 |
Carcinoembryonic antigen-related cell adhesion molecule-1 | 85 | 98 |
Ca 19-9 | 80 | 73 |
SPan-1 | 81-94 | 75 |
DUPAN-2 | 48-80 | 75-85 |
Macrophage inhibitory cytokine 1 | 90 | 62 |
Alpha4GnT | 76 | 83 |
PAM4 | 77 | 95 |
Pancreatic juice DNA methylation | 82 | 100 |
Fecal K-ras | 77 | 81 |
Table 5 Level of risk according to cumulative risk factors
Factors | Risk level |
Race/sex: Male; black; Ashkenazi Jewish descent. Exposures: obesity; smoking; diabetes mellitus; Helicobacter pylori infection.Family history: Cancer history in a first-degree relative; history of pancreatic cancer in one first-degree relative. Inherited conditions: Hereditary non-polyposis colorectal cancer; familial adenomatous polyposis; BRCA1 mutation carrier | Low (less than 5-fold) |
Family history: History of pancreatic cancer in two first-degree relatives. Inherited conditions: cystic fibrosis; BRCA2 mutation carrier. Comorbidity: Chronic pancreatitis | Moderate (5- to 10-fold) |
Inherited conditions: FAMMM kindreds with p16 germline mutation and at least one case of pancreatic cancer in a first-degree or second-degree relative; hereditary pancreatitis; Peutz–Jeghers syndrome; BRCA2 or BRCA1 mutation carrier with at least one case of pancreatic cancer in a first-degree or second-degree relative. Family history: Three or more first-degree; second-degree or third-degree relatives with pancreatic cancer | High (greater than 10-fold) |
- Citation: Zavoral M, Minarikova P, Zavada F, Salek C, Minarik M. Molecular biology of pancreatic cancer. World J Gastroenterol 2011; 17(24): 2897-2908
- URL: https://www.wjgnet.com/1007-9327/full/v17/i24/2897.htm
- DOI: https://dx.doi.org/10.3748/wjg.v17.i24.2897