Early-onset gastric cancer: Learning lessons from the young

Table 1 Environmental and other risk factors for conventional gastric cancer

Increased risk of gastric cancer	Decreased risk of gastric cancer
CHD1, TP53, BRCA2 germline mutation	Fruit and vegetables
Hereditary non-polyposis colorectal cancer	Ascorbic acid
Helicobacter pyloriinfection	Carotenoids
Ebstein barrvirus infection	Folates
Cigarette smoking	Tocopherols
Smoked or cured meat and fish	Cereal fibres
Pickled vegetables	Numerous polymorphisms (as mentioned under increased risk)
Chilli peppers
Alcohol
Exposure to nitrosamines + inorganic dust
Obesity
Pharmacological gastric acid suppression
IL-1β-31 polymorphism
1195 COX-2 polymorphism
Other polymorphisms: MTHFR, PSCA, XPA, XPC, ERCC2, GSTT1, SULT1A1, NAT2, EPHX1, Toll-like receptor 4

Table 2 Clinico-pathological and molecular-genetic differences between early-onset and conventional gastric cancers

Conventional gastric cancer	Early-onset gastric cancer	Ref.
Equally common in male and females	More common in females	[13,28,30,31]
Intestinal type cancer more common	Diffuse type cancer more common	[13,28]
Usually unifocal	Often multifocal	[32,33]
Often preceded by intestinal metaplasia	No intestinal metaplasia	[13,28]
Microsatellite Instability in 15%-20%	Lack of MSI	[24,29,41-43]
Commonly find loss of heterozygosity	Infrequent loss of heterozygosity	[24]
COX2 overexpression in 66%	COX2 overexpression in 10%	[46]
Loss of TFF1 expression in 73%	Loss of TFF1 expression in 39%	[46]
Loss of RUNX3 gene	No loss of RUNX3	[58-61]
Widespread gains throughout genome	Gains at chromosomes 17q, 19q and 20q	[40]
Distinct gene clusters on hierarchical analysis	Distinct gene clusters on hierarchical analysis	[39]
Infrequent LMW isoforms of cyclin E	Frequent LMW isoforms of cyclin E	[52]
CD44v6 expression	CD44v6 more commonly expressed	[57]
Usually no family history	10% with a family history	[13]