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Etiology of Pancreatic Cancer

Pancreatic cancer is fundamentally a disease caused by damage to the DNA. This


damage is often referred to as mutations. As individuals with an inherited cancer syndrome
age, some of will sustain damage the good copy of the gene in a cell in their pancreas. That cell
will then have two damaged copies of the gene (one inherited and one acquired during life),
and, as a result, that cell in the pancreas will begin to grow abnormally and will eventually
form a cancer. The second way that can damage the DNA is with individuals’behavior. For
example, the carcinogens (cancer causing chemicals) in cigarette smoke can damage our DNA.
If the carcinogens damage a key cancer-associated gene in a cell in the pancreas, then that cell
may grow into a cancer(1). There are some risk factors that made individuals prone to
pancreatic cancer :
1. Family history and genetic factors
A family history of pancreatic cancer is an important risk factor for disease
about 7–10% of affected individuals have a family history(2). Approximately 5-10% of
patients with pancreatic carcinoma have some genetic predisposition to developing the
disease(3). The most frequent genetic abnormalities in invasive pancreatic
adenocarcinomas are mutational activation of the KRAS oncogene, inactivation of
tumour-suppressor genes including CDKN2A, TP53, SMAD4, and BRCA2 widespread
chromosomal losses, gene amplifications,and telomere shortening(2).

2. Smoking
A meta-analysis of 12 studies of approximately 1.500 patients with PC
associated levels of smoking with PC. The excess risk of PC was more than 2-fold
(relative risk, 2.4) among subjects who smoked less than one pack/day and more than
3-fold (relative risk, 3.3) among those who smoked one or more packs/day. Studies
have consistently confirmed the relationship between smoking and pancreatic cancer,
with smokers having about a 2-fold excess risk compared with nonsmokers(4).
Tobacco smoking releases many carcinogens. Several gene products mediate
the degradation of tobacco carcinogens; a recent study examined several detoxifying
genes in 455 patients with pancreatic cancer. 50 Variants in genes, such as CYP1B1-
4390-GG and uridine 5=-diphosphoglucuronosyltransferase, reduced the risk of
pancreatic cancer, whereas variants in others, such as GSTM1, increased risk. Little is
known about the mechanisms by which these genes affect the risk of cancer, but their
products could affect the inflammatory response, fibrosis, cell proliferation, and other
processes involved in carcinogenesis(5).

3. Diet and Obesity


A Mediterranean dietary pattern, when combined with other factors indicative
of a healthy lifestyle, protects against pancreatic cancer(6). Red meats, particularly
when cooked at high temperatures, increase the risk of pancreatic cancer. Based on data
from more than 500.000 persons in 10 countries, consumption of fruit and vegetables
does not decrease the risk of pancreatic cancer. Similarly, carbohydrate intake was not
associated with risk of pancreatic cancer(7).
Obesity is also a risk factor for several types of cancer, including pancreatic
cancer. A meta-analysis of 6391 patients with pancreatic cancer found a relative risk of
1.19 for cancer among obese persons compared with persons of normal weight. The
available data for obesity are stronger than that for diet and reinforce the concept that
maintaining a healthy body weight can prevent pancreatic cancer(8).

4. Others medical condition


a. Diabetes Mellitus type 2
Clinicians are aware that new-onset diabetes can be a symptom of pancreatic
cancer, particularly in low-weight, middle-aged, or older patients with no family
history of this disease. A systematic review of 30 studies concluded that patients
with diabetes mellitus of at least 5-years' duration have a 2-fold increased risk of
developing pancreatic carcinoma. Pancreatic cancer may follow 18-36 months after
a diagnosis of diabetes mellitus in elderly patients with no family history of diabetes
mellitus(3).
b. Chronic pancreatitis
Chronic pancreatitis is a substantial risk factor for the development of pancreatic
cancer. A multicenter study of more than 2000 patients with chronic pancreatitis
showed a 26-fold increase in the risk of developing pancreatic cancer. This risk
increased linearly with time, with 4% of patients who had chronic pancreatitis for 20
years' duration developing pancreatic cancer(9).
References
1. Medicine JH. What Causes Pancreatic Cancer [Internet]. 2014. Available from:
http://pathology.jhu.edu/pc/BasicCauses.php?area=ba
2. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet.
Elsevier Ltd; 2011;378(9791):607–20.
3. Dragovich T. Pancreatic Cancer : Practice Essentials, Background, Pathophysiology
[Internet]. Medscape; 2012. Available from:
http://emedicine.medscape.com/article/280605-overview#a4
4. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer.
Gastroenterology. Elsevier Inc.; 2013;144(6):1252–61.
5. Pandol SJ, Apte M V., Wilson JS, Gukovskaya AS, Edderkaoui M. The burning
question: Why is smoking a risk factor for pancreatic cancer? Pancreatology. Elsevier
India, a division of Reed Elsevier India Pvt. Ltd; 2012;12(4):344–9.
6. Study H. A Combined Healthy Lifestyle Score and Risk of Pancreatic Cancer in a Large
Cohort Study. 2015;169(8):764–70.
7. Jiao L, Flood A, Subar AF, Hollenbeck AR, Schatzkin A, Stolzenberg-Solomon R.
Glycemic index, carbohydrates, glycemic load, and the risk of pancreatic cancer in a
prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1144–51.
8. Berrington de Gonzalez A, Sweetland S, Spencer E. A meta-analysis of obesity and the
risk of pancreatic cancer. Br J Cancer. 2003;89(3):519–23.
9. Gold EB, Cameron JL. Chronic Pancreatitis and Pancreatic Cancer. N Engl J Med.
1993;328.

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