Pancreatic cancer risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Aravind Reddy Kothagadi M.B.B.S[2]

## Overview

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Pancreatic cancer is associated with number of predisposing risk factors such as age, gender, ethnicity, and environmental exposures. The most potent risk factors for pancreatic cancer include smoking, alcoholism, increased BMI, diabetes mellitus, chronic pancreatitis and a family history of pancreatic cancer. Individuals with hereditary pancreatitis, familial pancreatic cancer, Peutz-Jeghers disease, familial atypical multiple mole melanoma syndrome (FAMMM), von Hippel-Lindau syndrome, multiple endocrine neoplasia type 1, cystic fibrosis of the pancreas and familial cancer syndromes such as lynch syndrome, familial adenomatous polyposis (FAP) and hereditary breast and ovarian cancer-BRCA1 and BRCA2 mutations are also at an increased risk of pancreatic cancer. Other medical conditions which pose as a risk factor for pancreatic cancer are inflammatory bowel disease, periodontal disease and peptic ulcer disease.

## Risk Factors

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* The most potent risk factors for pancreatic cancer include smoking, alcoholism, increased BMI, diabetes mellitus, chronic pancreatitis and a family history of pancreatic cancer.
* Individuals with the following conditions are also at an increased risk of pancreatic cancer:[1][2][3]

*     * Hereditary pancreatitis
* Familial pancreatic cancer
* Peutz-Jeghers disease
* Familial atypical mole melanoma syndrome (FAMMM)
* Cystic fibrosis of pancreas
* Familial cancer syndromes such as:
* Lynch syndrome
* Familial adenomatous polyposis (FAP)
* Von Hippel-Lindau syndrome
* Multiple endocrine neoplasia type 1
* Hereditary breast and ovarian cancer-BRCA1 and BRCA2 mutations

* Risk factors for Pancreatic cancer are illustrated in the following tables:

* Risk factors for Pancreatic Cancers:[4]

Risk factors for Pancreatic Cancer

Risk factors

* Smoking

* Alcohol

* Increased BMI

* Diabetes mellitus

* Chronic pancreatitis

* Family history of pancreatic cancer

Familial Cancer Syndromes

* BRCA1, BRCA2

* Familial adenomatous polyposis (FAP)

* Peutz-Jeghers syndrome

* Familial atypical multiple mole melanoma syndrome (FAMMM)

* Lynch syndrome

* Von Hippel-Lindau syndrome

* Multiple endocrine neoplasia type 1

* Gardner syndrome

Other medical conditions

* Inflammatory bowel disease

* Periodontal disease

* Peptic ulcer disease

* Risk Factors and Inherited Syndromes associated with Pancreatic Cancer:[5]

Risk Factors and Inherited Syndromes associated with Pancreatic Cancer

Risk Factor | Approximate Risk
Smoking | 2-3 %
Long-standing Diabetes mellitus | 2 %
Nonhereditary and chronic pancreatitis | 2-6 %
Obesity, Inactivity or both  | 2 %
Non O Blood Group  | 1-2 %
Genetic Syndrome and Associated Gene or Genes
Hereditary pancreatitis (PRSS1, SPINK1)  | 50 %
Familial atypical multiple mole and melanoma syndrome (p16)  | 10-20 %
Hereditary breast and ovarian cancer syndromes (BRCA1, BRCA2, PALB2)  | 1-2 %
Peutz-Jeghers syndrome (STK11 [LKB1])  | 30-40 %
Hereditary nonpolyposis colorectal cancer (Lynch syndrome) (MLH1, MSH2, MSH6)  | 4 %
Ataxia-telangiectasia (ATM)  | Unknown
Li-Fraumeni syndrome (P53)  | Unknown

### Early-Onset Pancreatic Cancer

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Early-Onset Pancreatic Cancer is defined as pancreatic cancer at age of onset less than 50 years.

Risk Factors for Early-Onset Pancreatic Cancer

Alcohol*
Metabolic dysfunction with associated Steatotic Liver Disease
Obesity
Sedentary lifestyle
Smoking

*Alcohol consumption of more than 26g/day compared to less than 26g/day was associated with early-onset pancreatic cancer, particularly among individuals younger than 45 years.[6]

Following risk factors were more strongly associated with early-onset pancreatic cancer than with later-onset pancreatic cancer[7]:

* Diabetes
* Non-O Blood Group
* Non-O Blood Group was more strongly associated with pancreatic risk among participants aged 70 years or younger vs those older than 70 years.
* Obesity
* Smoking
* Tall Height
* Those with early-onset pancreatic cancer were more likely to have a family history of pancreatic cancer were more likely to have a family history of pancreatic cancer in a first degree relative.[6]

## References

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1. ↑ Goral V (2015). "Pancreatic Cancer: Pathogenesis and Diagnosis". Asian Pac J Cancer Prev. 16 (14): 5619–24. PMID 26320426.
2. ↑ Pandol, Stephen; Gukovskaya, Anna; Edderkoui, Mouad; Dawson, David; Eibl, Guido; Lugea, Aurelia (2012). "Epidemiology, risk factors, and the promotion of pancreatic cancer: Role of the stellate cell". Journal of Gastroenterology and Hepatology. 27: 127–134. doi:10.1111/j.1440-1746.2011.07013.x. ISSN 0815-9319.
3. ↑ Lowenfels, Albert B.; Maisonneuve, Patrick (2005). "Risk factors for pancreatic cancer". Journal of Cellular Biochemistry. 95 (4): 649–656. doi:10.1002/jcb.20461. ISSN 0730-2312.
4. ↑ Bond-Smith G, Banga N, Hammond TM, Imber CJ (2012). "Pancreatic adenocarcinoma". BMJ. 344: e2476. doi:10.1136/bmj.e2476. PMID 22592847.CS1 maint: Multiple names: authors list (link)
5. ↑ Ryan DP, Hong TS, Bardeesy N (2014). "Pancreatic adenocarcinoma". N Engl J Med. 371 (11): 1039–49. doi:10.1056/NEJMra1404198. PMID 25207767.CS1 maint: Multiple names: authors list (link)
6. ↑ 6.0 6.1 McWilliams RR, Maisonneuve P, Bamlet WR, et al. Risk factors for early-onset and very-early-onset pancreatic adenocarcinoma: a Pancreatic Cancer Case-Control Consortium (PanC4) analysis. Pancreas. 2016;45(2):311-316. doi:10.1097/MPA.0000000000000392
7. ↑ Yuan C, Kim J, Wang QL, et al; PanScan/PanC4 I-III Consortium. The age-dependent association of risk factors with pancreatic cancer. Ann Oncol. 2022;33(7):693-701. doi:10.1016/j.annonc.2022.03. 276

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