Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes

Table 1 Summary of modifiable risk factors associated with pancreatic cancer

Factor	Direction of association	Strength of association	Type of studies conducted	Related notable findings	Ref.
Smoking	Positive	Strong association; 74% increased risk in current smokers; 20% increased risk in former smokers	Case-control, cohort, nested case-control studies	Dose responsive; risk remains 10-20 yr following smoking cessation	[18-20]
Alcohol	Mixed between no association and positive	Various; 15%-43% increased risk in meta-analysis	Meta-analysis of cohort studies	Dose responsive; sex dependent; Increased risk in spirit drinkers; link with chronic pancreatitis which is a risk factor for pancreatic cancer	[9,21-24]
Obesity	Positive	10% increased risk for every 5 BMI units	Cohort studies	Link with Type 2 diabetes which is associated with increased risk of pancreatic cancer	[25]
Dietary factors	Variable	Non-significant positive association for red meat; 17% increased risk associated with 50 g/d of processed meat consumption compared to 20 g/d	Cohort studies	Overall consensus cannot be made and further research is required	[25]
Helicobacter pylori	Positive	45% increased risk	Meta-analysis of case-control studies	Significant publication bias and small numbers included therefore further studies are required	[26]

BMI: Body mass index.

Table 2 Range of increased relative risk of pancreatic cancer associated with specific syndromes as summarised by Chen et al[30] and Del Chiaro et al[31]

Gene	Syndrome	Increase relative risk vs general population
		Chen et al[30]	Del Chiaro et al[31]
BRCA2	Hereditary breast and ovarian cancer	2.2-5.9
BRCA1		1.6-4.7
STK11	Peutz-Jeghers syndrome	76.2-139.0	132.0
PRSS1	Hereditary pancreatitis	53-87	50-70
CDKN2A	Familial atypical multiple mole melanoma	14.8-80.0	34-39
MMR	Hereditary nonpolyposis colorectal cancer	0.0-10.7	4.7

Table 3 Summary of impact of dietary factors, nutrition and physical activity on pancreatic cancer risk

	Diet, nutrition, physical activity and pancreatic cancer
		Decreases risk	Increases risk
Strong evidence	Convincing		Body fatness
	Probable		Adult attained height
Limited evidence	Limited - suggestive		Red meat, Processed meat; alcoholic drinks (heavier drinking); foods and beverages containing fructose; foods containing saturated fatty acids
	Limited - no conclusion	Physical activity; fruits; vegetables; folate; fish; eggs; tea; soft drinks; coffee; carbohydrates; sucrose; glycaemic index; glycaemic load; total fat; monounsaturated fat; polyunsaturated fats; dietary cholesterol; vitamin C; and multivitamin/mineral supplements
Strong evidence	Substantial effect on risk unlikely

Adapted from World Cancer Research Fund Continuous Update Project[25].

Table 4 Summary of the different subtypes of pancreatic ductal adenocarcinoma[52]

Morphological Variant	Characteristics
Adenosquamous carcinoma	Significant components of ductal/glandular and squamous differentiation (at least 30%). Considered to have a worse prognosis than pancreatic adenocarcinoma.
Colloid/mucinous carcinoma	Production of copious amounts of extracellular stromal mucin. Most arise in association with intraductal papillary mucinous neoplasms; thought to have more favourable prognosis than pancreatic adenocarcinoma
Undifferentiated/anaplastic carcinoma	Minimal or no differentiation; highly atypical cells which may appear spindle shaped or sarcomatoid, often admixed with osteoclast-like giant cells. One of the most aggressive forms of pancreatic cancer with extremely poor survival rates
Signet ring cell carcinoma	Discohesive, singly invasive cells with intracytoplasmic mucin that may displace the nucleus. Similar tumours throughout the gastrointestinal tract. Very rare form of pancreatic cancer with prognosis similar to that of pancreatic adenocarcinoma
Medullary carcinoma	Syncytial arrangement of pleomorphic epithelial cells with associated intratumoral lymphoid infiltrate. Prognosis is slightly better than pancreatic adenocarcinoma
Hepatoid carcinoma	Morphological similarity to hepatocellular carcinoma. May produce bile. Very rare tumour with a poor prognosis similar to that of pancreatic adenocarcinoma