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Pancreatic Cancer

November 15, 2017

Disease synonyms

Pancreatic cancer, Pancreatic carcinoma, Pancreatic adenocarcinoma, PC, Familial pancreatic cancer, FPC, Pancreatic ductal adenocarcinoma, PDAC


Inheritance pattern

Autosomal dominant, somatic


Clinical features

Pancreatic cancer is one of the world’s most lethal malignant neoplasms, with a 5-year survival rate of about 5-7%1, 2, 6.

Pancreatic cancer now represents the fourth to fifth most frequent cause of cancer mortality in North America, Europe, and Japan3, 4. The incidence of pancreatic cancer varies greatly across regions and populations. Incidence rates for pancreatic cancer are highest in Northern America (7.4 per 100000 people) and Western Europe (7.3 per 100000), followed by other regions in Europe and Australia/New Zealand (~ 6.5 per 100000)6.

Approximately 75% of all pancreatic carcinomas occur within the head or neck of the pancreas, 15-20% occur in the body of the pancreas, and 5-10% occur in the tail7. The two main tumor types of pancreatic cancer are adenocarcinoma (which accounts for about 85% of cases), and pancreatic endocrine tumors (which comprise fewer than 5% of all cases)8.

Pancreatic cancer symptoms infographics

Typical presenting symptoms of pancreatic cancer include abdominal or mid-back pain, obstructive jaundice, and weight loss. Pancreatic-duct obstruction could result in attacks of pancreatitis. Gastric-outlet obstruction with nausea and vomiting sometimes happens with more advanced disease. Deep and superficial venous thrombosis is not unusual and might be a presenting sign of malignant disease. About 25% of patients with pancreatic cancer have diabetes mellitus at diagnosis and roughly another 40% have impaired glucose tolerance. Less common manifestations include panniculitis and depression.

Early-stage pancreatic cancer is usually clinically silent, and the disease only becomes apparent after the tumor invades the surrounding tissues. Most people who present with symptoms attributable to pancreatic cancer already have the advanced disease.

Risk factors for pancreatic cancer include smoking, a family history of chronic pancreatitis, advancing age, male sex, diabetes mellitus, obesity, non-O blood group, occupational exposures, African-American ethnic origin, a high-fat diet, diets high in meat and low in vegetables and folate, and possibly Helicobacter pylori infection and periodontal disease3, 6.

Approximately 20% of hereditary cases of PC are currently attributed to a known genetic syndrome4, 9. The term familial pancreatic cancer (FPC) applies to the remaining 80% of patients with an inherited predisposition: families in which at least two first-degree relatives (FDRs) have been diagnosed with PC but that do not meet the diagnostic criteria for the previous settings4.

Numerous hereditary cancer syndromes are known to be associated with an increased risk of pancreatic cancer, including Peutz-Jeghers syndrome (PJS), melanoma pancreatic-cancer syndrome (MPCS) or familial atypical multiple mole melanoma (FAMMM)-PC, hereditary breast-ovarian cancer (HBOC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP). In addition, an increased risk of PC is present in patients with hereditary pancreatitis or cystic fibrosis4, 9, 6.

Several pancreatic cancer genes have been established, including high-penetrance genes such as BRCA2, STK11, CDKN2A, PALB2 and others (see table).


Gene OMIM (Gene) Associated diseases (OMIM) Inheritance
APC 611731 colorectal cancer; Hepatocellular Carcinoma; Desmoid disease, hereditary; familial adenomatous polyposis; Gastric Cancer AD
ATM 607585 familial breast-ovarian cancer type 2; ataxia-telangiectasia AD, AR
AXIN2 604025 colorectal cancer; oligodontia-colorectal cancer syndrome AD
BLM 604610 Bloom syndrome AR
BMPR1A 601299 Juvenile polyposis syndrome, infantile form AD
BRCA1 113705 familial breast-ovarian cancer type 1; pancreatic cancer type 4; Fanconi anemia, complementation group S AD, AR
BRCA2 600185 familial breast-ovarian cancer type 2; Medulloblastoma; Prostate Cancer; Wilms tumor, type 1; Fanconi anemia complementation group D1; pancreatic cancer type 2 AD, AR
CDH1 192090 familial breast-ovarian cancer type 2; blepharocheilodontic syndrome 1; Gastric Cancer, Hereditary Diffuse; Ovarian Cancer; Prostate Cancer; endometrial cancer AD
CDKN2A 600160 Malignant melanoma 2; Pancreatic cancer/melanoma syndrome AD
CHEK2 604373 familial breast-ovarian cancer type 2; Prostate Cancer; Osteogenic Sarcoma; Li-Fraumeni syndrome 2 AD
EPCAM 185535 Diarrhea 5, with tufting enteropathy, congenital; Colorectal cancer, hereditary nonpolyposis, type 8 AR
FLCN 607273 colorectal cancer; Birt-Hogg-Dube syndrome; Renal carcinoma, chromophobe, somatic; primary spontaneous pneumothorax AD
GALNT12 610290 Colorectal cancer, susceptibility to, 1
MLH1 120436 Muir-Torre syndrome; mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-2 AD, AR
MLH3 604395 colorectal cancer; endometrial cancer; Colorectal cancer, hereditary nonpolyposis, type 7 AD
MSH2 609309 Lynch syndrome; Muir-Torre syndrome; mismatch repair cancer syndrome AD, AR
MSH3 600887 endometrial cancer; Familial adenomatous polyposis 4 AR
MSH6 600678 mismatch repair cancer syndrome; endometrial cancer; hereditary nonpolyposis colorectal cancer-5 AD, AR
MUTYH 604933 familial adenomatous polyposis type 2; Gastric Cancer AR
NBN 602667 Nijmegen breakage syndrome; Aplastic Anemia; Acute lymphoblastic leukemia AR
NTHL1 602656 Familial adenomatous polyposis 3 AR
PALB2 610355 familial breast-ovarian cancer type 2; Fanconi anemia of complementation group N; Pancreatic cancer, susceptibility to, 3 AD
PMS2 600259 mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-4 AR
POLD1 174761 Colorectal cancer, susceptibility to type 10; MANDIBULAR HYPOPLASIA, DEAFNESS, PROGEROID FEATURES, AND LIPODYSTROPHY SYNDROME AD
POLE 174762 Colorectal cancer, susceptibility to, 12; FILS syndrome AD, AR
PRSS1 276000 hereditary pancreatitis AD
PTEN 601728 Cowden syndrome 1; Cowden syndrome type 2; Bannayan-Riley-Ruvalcaba syndrome; Prostate Cancer; Macrocephaly/autism syndrome; Meningioma, familial, susceptibility to AD
RNF43 612482 AD
SMAD4 600993 Myhre syndrome; Juvenile polyposis syndrome, infantile form; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Pancreatic Cancer AD
STK11 602216 Peutz-Jeghers syndrome; Pancreatic Cancer; Spermatocytic seminoma, somatic AD
TGFBR2 190182 Esophageal cancer, somatic; Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6 AD
TP53 191170 familial breast-ovarian cancer type 2; colorectal cancer; Hepatocellular Carcinoma; Glioma susceptibility 1; Li-Fraumeni syndrome 1; Osteogenic Sarcoma; Pancreatic Cancer AD
VHL 608537 Renal carcinoma, chromophobe, somatic; pheochromocytoma; von Hippel-Lindau disease; Erythrocytosis, familial, 2 AD, AR

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance
ABRAXAS1 611143
APC 611731 colorectal cancer; Hepatocellular Carcinoma; Desmoid disease, hereditary; familial adenomatous polyposis; Gastric Cancer AD
ATM 607585 familial breast-ovarian cancer type 2; ataxia-telangiectasia AD, AR
AXIN2 604025 colorectal cancer; oligodontia-colorectal cancer syndrome AD
BAP1 603089 Tumor predisposition syndrome AD
BARD1 601593 familial breast-ovarian cancer type 2 AD
BLM 604610 Bloom syndrome AR
BMPR1A 601299 Juvenile polyposis syndrome, infantile form AD
BRCA1 113705 familial breast-ovarian cancer type 1; pancreatic cancer type 4; Fanconi anemia, complementation group S AD, AR
BRCA2 600185 familial breast-ovarian cancer type 2; Medulloblastoma; Prostate Cancer; Wilms tumor, type 1; Fanconi anemia complementation group D1; pancreatic cancer type 2 AD, AR
BRIP1 605882 familial breast-ovarian cancer type 2; Fanconi anemia of complementation group J AD
CDH1 192090 familial breast-ovarian cancer type 2; blepharocheilodontic syndrome 1; Gastric Cancer, Hereditary Diffuse; Ovarian Cancer; Prostate Cancer; endometrial cancer AD
CDK4 123829 Melanoma, Cutaneous Malignant, Susceptibility To, 3 AD
CDKN2A 600160 Malignant melanoma 2; Pancreatic cancer/melanoma syndrome AD
CHEK2 604373 familial breast-ovarian cancer type 2; Prostate Cancer; Osteogenic Sarcoma; Li-Fraumeni syndrome 2 AD
DICER1 606241 Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma AD
DIS3L2 614184 Perlman syndrome AR
EPCAM 185535 Diarrhea 5, with tufting enteropathy, congenital; Colorectal cancer, hereditary nonpolyposis, type 8 AR
FANCC 613899 Fanconi anemia of complementation group C AR
FH 136850 Leiomyomatosis and renal cell cancer; Fumarase deficiency AD, AR
FLCN 607273 colorectal cancer; Birt-Hogg-Dube syndrome; Renal carcinoma, chromophobe, somatic; primary spontaneous pneumothorax AD
GALNT12 610290 Colorectal cancer, susceptibility to, 1
HNF1B 189907 noninsulin-dependent diabetes mellitus / Diabetes mellitus type II; MODY type 5; Renal carcinoma, chromophobe, somatic AD
HOXB13 604607 Hereditary prostate cancer type 9
KIT 164920 Mast cell disease; Piebaldism; Spermatocytic seminoma, somatic; acute myeloid leukemia; gastrointestinal stromal tumor AD
MC1R 155555 oculocutaneous albinism type 2; skin/hair/eye pigmentation 2; Melanoma, cutaneous malignant, susceptibility to, 5 AR
MEN1 613733 multiple endocrine neoplasia type 1 AD
MET 164860 Hepatocellular Carcinoma; Renal cell carcinoma, papillary; deafness type 97 AD, AR
MITF 156845 Albinism, Ocular, With Sensorineural Deafness; Tietz Syndrome; Waardenburg syndrome type 2A; Melanoma, Cutaneous Malignant, Susceptibility To, 8 AD, AR
MLH1 120436 Muir-Torre syndrome; mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-2 AD, AR
MLH3 604395 colorectal cancer; endometrial cancer; Colorectal cancer, hereditary nonpolyposis, type 7 AD
MRE11 600814 Ataxia-telangiectasia-like disorder type 1 AR
MSH2 609309 Lynch syndrome; Muir-Torre syndrome; mismatch repair cancer syndrome AD, AR
MSH3 600887 endometrial cancer; Familial adenomatous polyposis 4 AR
MSH6 600678 mismatch repair cancer syndrome; endometrial cancer; hereditary nonpolyposis colorectal cancer-5 AD, AR
MUTYH 604933 familial adenomatous polyposis type 2; Gastric Cancer AR
NBN 602667 Nijmegen breakage syndrome; Aplastic Anemia; Acute lymphoblastic leukemia AR
NF1 613113 neurofibromatosis type 1; Neurofibromatosis-Noonan syndrome; Leukemia, juvenile myelomonocytic AD
NTHL1 602656 Familial adenomatous polyposis 3 AR
PALB2 610355 familial breast-ovarian cancer type 2; Fanconi anemia of complementation group N; Pancreatic cancer, susceptibility to, 3 AD
PMS1 600258
PMS2 600259 mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-4 AR
POLD1 174761 Colorectal cancer, susceptibility to type 10; MANDIBULAR HYPOPLASIA, DEAFNESS, PROGEROID FEATURES, AND LIPODYSTROPHY SYNDROME AD
POLE 174762 Colorectal cancer, susceptibility to, 12; FILS syndrome AD, AR
POT1 606478 Melanoma, cutaneous malignant, susceptibility to, 10 AD
PRSS1 276000 hereditary pancreatitis AD
PTCH1 601309 Gorlin syndrome; Holoprosencephaly-7 AD
PTEN 601728 Cowden syndrome 1; Cowden syndrome type 2; Bannayan-Riley-Ruvalcaba syndrome; Prostate Cancer; Macrocephaly/autism syndrome; Meningioma, familial, susceptibility to AD
RAD50 604040 Nijmegen breakage syndrome-like disorder
RAD51C 602774 Fanconi anemia of complementation group O; Breast-ovarian cancer, familial, susceptibility to, 3 AR
RAD51D 602954 susceptibility to familial breast-ovarian cancer type 4
RECQL 600537
RET 164761 Hirschsprung disease; familial medullary thyroid carcinoma; multiple endocrine neoplasia 2B; pheochromocytoma; multiple endocrine neoplasia 2A; congenital central hypoventilation syndrome AD
RNF43 612482 AD
SDHA 600857 mitochondrial complex II deficiency; Leigh syndrome; dilated cardiomyopathy-1GG; paragangliomas type 5 AD, AR, M
SDHAF2 613019 paragangliomas type 2 AD
SDHB 185470 paragangliomas type 4; pheochromocytoma; gastrointestinal stromal tumor; paraganglioma and gastric stromal sarcoma AD
SDHC 602413 Paragangliomas 3; gastrointestinal stromal tumor; paraganglioma and gastric stromal sarcoma AD
SDHD 602690 paragangliomas 1; pheochromocytoma; mitochondrial complex II deficiency; paraganglioma and gastric stromal sarcoma AD, AR
SMAD4 600993 Myhre syndrome; Juvenile polyposis syndrome, infantile form; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Pancreatic Cancer AD
SMARCA4 603254 Rhabdoid tumor predisposition syndrome 2; mental retardation-16 AD
STK11 602216 Peutz-Jeghers syndrome; Pancreatic Cancer; Spermatocytic seminoma, somatic AD
TGFBR2 190182 Esophageal cancer, somatic; Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6 AD
TP53 191170 familial breast-ovarian cancer type 2; colorectal cancer; Hepatocellular Carcinoma; Glioma susceptibility 1; Li-Fraumeni syndrome 1; Osteogenic Sarcoma; Pancreatic Cancer AD
TSC1 605284 tuberous sclerosis type 1 AD
TSC2 191092 tuberous sclerosis-2 AD
VHL 608537 Renal carcinoma, chromophobe, somatic; pheochromocytoma; von Hippel-Lindau disease; Erythrocytosis, familial, 2 AD, AR
WT1 607102 Frasier syndrome; Mesothelioma, somatic; Wilms tumor, type 1; Denys-Drash syndrome; Nephrotic syndrome, type 4; Meacham syndrome AD
XRCC2 600375 Fanconi anemia, complementation group U AR
XRCC3 600675 familial breast-ovarian cancer type 2 AD

With genetic testing, we are able today to analysis pancreatic cancer susceptibility for better planning of preventive cancer screening in at risk individuals and thereby able to detect cancer at early stage and to reduce cancer mortality. Genetic testing for pancreatic cancer is the most accurate means of determining the genetic risk of pancreatic cancer.

The only potentially curative treatment for pancreatic cancer is surgical resection. Early detection of disease with curative resection has been shown to improve 5-year survival rates up to 60% 5. In addition, an important role exists for chemotherapy and/or radiation therapy.


Differential diagnosis

The differential diagnosis of pancreatic cancer-related disorders – depending on the major symptoms in the initial case – includes the following diseases1:

  • Acute pancreatitis
  • Chronic pancreatitis
  • Cholangitis and/or cholecystitis, cholelithiasis
  • Choledochal cysts
  • Gastric cancer/peptic ulcer disease

Testing strategy

CENTOGENE offers an advanced, fast and cost-effective strategy to test large NGS panels and diagnose complex phenotypes based on PCR-free whole genome sequencing and NGS technology. This approach offers an unparalleled advantage by reducing amplification/capture biases and providing sequencing of the entire gene with more uniform coverage.

To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for pancreatic cancer using NGS Panel Genomic targeted towards this specific phenotype:

Step 1: Whole genome sequencing from a single filter card. The sequencing covers the entire gene (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the pancreatic cancer panel. Copy Number Variants analysis derived from NGS data is also included.

Step 2: If no pathogenic variants is identified after analysis of the Pancreatic cancer panel, we further recommend continuing the bioinformatics analysis of the data using whole genome sequencing to cover those genes which are either implicated in an overlapping phenotype or could be involved in a similar pathway but are not strongly clinically implicated based on the current information in literature.


Referral reasons

Genetic testing for pancreatic cancer is recommended for people who show one or more of the following features:

  • History of colon or any gastrointestinal cancer
  • Positive family history of pancreatic cancer and premalignant gastrointestinal conditions
  • Present endocrinological and/or gastrointestinal conditions and family history of cancer
  • History of chronic and complex gastrointestinal condition.

Test utility

Sequencing, deletion/duplication of pancreatic cancer related genes should be performed in all individuals suspected of having pancreatic cancer. In parallel, other genes reported to be related with this clinical phenotype should also be analyzed for the presence of pathogenic variants, due to the overlap in many clinical features caused by those particular genes.

Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family with the natural history of pancreatic cancer, identify at-risk family members, provide information about reproductive risks as well as preconception/prenatal options, and allow for appropriate referral for patient support and/or resources.