Microbiome and pancreatic cancer: A comprehensive topic review of literature

Table 2 Helicobacter pylori and pancreatic cancer

Ref.	Study Design	Case No.	Control No.	Detection	Bacteria association	Outcome	Author conclusion
				Method
Raderer et al[33], 1998, Austria	Case-control	92	27	Plasma IgG ELISA	H. pylori	OR = 2.1	H. pylori seropositivity prominent in pancreatic cancer patients compared with colorectal cancer combined with normal controls
						95%CI: 1.1-4.1
						P = 0.035
Stolzenberg-Solomon et al[34] 2001, Finland	Nested case-control	121	226	Plasma IgG ELISA	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	H. pylori	Male smokers seropositive for H. pylori were nearly twice as likely to develop pancreatic cancer compared to seronegative. Stronger influence adjusting for years of smoking
						OR = 1.87;
						95%CI: 1.05-3.34
						CagA+ strains
						OR = 2.01;
						95%CI: 1.09-3.70
de Martel et al[35], 2008, United States	Nested Case-control	104	262	Plasma IgG ELISA	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	H. pylori	H. pylori infection is not associated with development of pancreatic cancer
						OR = 0.85;
						95%CI: 0.49-1.48
						CagA+
						OR = 0.96;
						95%CI: 0.48-1.92
Lindkvist et al[36], 2008, Sweden	Nested Case-control	87	263	Plasma IgG ELISA	H. pylori	H. pylori overall	Adjusted risk for development of pancreatic cancer highly increased in never-smokers seropositive for H. pylori
						OR = 1.25
						95%CI: 0.75-2.09
						H. pylori in Never smokers
						AOR = 3.81
						95%CI: 1.06-13.63
Risch et al[37] 2010, United States	Case-control	373	690	Plasma IgG ELISA	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	CagA negative H. pylori non-O blood group	CagA-negative H. pylori seropositivity is a risk factor for pancreatic cancer among individuals with non–O blood type
						OR = 2.78,
						95%CI: 1.49-5.20,
						P = 0.0014;
						CagA negative H. pylori O-blood group
						OR = 1.28,
						95%CI: 0.62-2.64,
						P = 0.51
Trikudanathan et al[11], 2011	Meta-analysis	822	1513	meta-analysis of 6 case control studies	H. pylori	AOR = 1.38,	Significant positive association between the presence of H. pylori infection and pancreatic cancer.
						95%CI: 1.08-1.75
Gawin et al[38], 2012, Poland	Case-control	139	177	Plasma IGg, ELISA, western blot	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	H. pylori	No association between seropositivity of H. pylori or CagA with development of pancreatic cancer
						OR = 1.27;
						95%CI: 0.64-2.61
						P = 0.514
						CagA+
						OR = 0.90;
						95%CI: 0.46-1.73,
						P = 0.744
Xiao et al[39], 2013	Meta-analysis	1083	1950	meta-analysis of 9 case-control studies	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	H. pylori Overall	Borderline positive association H. pylori seropositivity overall. Adjusted risk for high quality studies revealed a significant, but modest association. CagA virulence seropositivity was not associated with pancreatic cancer
						OR = 1.47
						95%CI: 1.22-1.77
						Adjusted for “High quality” studies
						AOR = 1.28;
						95%CI: 1.01-1.63
						Adjusted for CagA positive
						AOR = 1.47;
						95%CI: 0.79-2.57
Yu et al[40], 2013, Finland	Case-control	353	353	multiplex serology to 4 H. pylori antigens	H. pylori	OR = 0.85;	No association between seropositivity of H. pylori with development of pancreatic cancer
						95%CI: 0.49 -1.49
Wang et al[41], 2014	Meta-analysis	2049	2861	Meta-analysis of 9 case-control studies (2 non- English language)	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	H. pylori overall	Eastern Asian populations demonstrate significant decreased risk pancreatic cancer associated with H. pylori seropositivity. No association present in Western populations
						OR = 1.06,
						95%CI: 0.74-1.37
						Eastern Asian Population
						H. pylori
						OR = 0.62,
						95%CI: 0.49-0.76
						Cag-A positive
						OR = 0.66,
						95%CI: 0.52-0.80
						Western European population
						H. pylori
						OR = 1.14
						95%CI: 0.89-1.40
						Cag-A positive
						OR = 0.84
						95%CI: 0.63-1.04
Risch et al[42], 2014, Shanghai	Case-control	761	794	Plasma IGg, ELISA	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	Cag-A positive H. pylori	Decreased pancreas-cancer risk was seen for CagA positive H. pylori compared to seronegativity for both H. pylori and CagA. A modest increased risk for CagA-negative H. pylori seropositivity
						AOR = 0.68;
						95%CI: 0.54-0.84
						Cag-A negative H. pylori
						AOR = 1.28;
						95%CI: 0.76-2.13
Chen et al[9], 2015	Meta-analysis	1446	2236	meta-analysis of 5 case control studies	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	Overall	CagA-negative, nonvirulent strains of H. pylori may be a risk factor for pancreatic cancer. No association with seropositivity for H. pylori infection overall, nor when adjusted for CagA or virulent strain infection
						OR = 0.99;
						95%CI: 0.65-1.50
						CagA+
						OR = 0.92;
						95%CI: 0.65 -1.3
						Virulent strain infection
						OR = 0.97
						95%CI: 0.50-1.89
						Nonvirulent infection
						OR = 1.47
						95%CI: 1.11-1.96
Schulte et al[10], 2015	Combination Case-control and meta-analysis	580	626	Plasma IGg, ELISA and meta-analysis of 10 case-control studies	cytotoxin-associated gene-A (CagA) virulence factor and H. pylori	H. pylori overall	No overall association observed for H. pylori seropositivity and risk of pancreatic cancer, but evidence of non-significant CagA strain-specific associations
						OR = 1.00
						95%CI: 0.74-1.35
						Cag-A negative
						AOR = 1.23
						95%CI: 0.83-1.82
						Cag-A positive
						OR = 0.74
						95%CI: 0.48-1.15