Role of gene polymorphisms in gastric cancer and its precursor lesions: Current knowledge and perspectives in Latin American countries

Table 1 Association studies of interleukin -1 gene cluster and gastric cancer/precancerous lesions

Year	Study population	Number of populations	Target genes and variants	Main findings associated with increased susceptibility
2004	Brazil Gatti et al[70]	56 GC; 56 ChrG	IL-1B-511C/T; -31T/C IL-1RN intron 2 VNTR	There was no association
2005	Costa RicaAlpizar-Alpizar et al[40]	58 GC; 41 nonneoplastic lesions; 58 cancer free patients; 41 healthy controls	IL-1B-511C/T; -31T/C; +3954C/TIL-10-1082G/A; -819C/T; -592C/A IL-1RN intron 2 VNTR	Carriers of the IL-1B+3954*T alle had an increased risk for developing GC (OR = 3.72, 95%CI: 1.34-10.2). IL-1RN heterozygote genotype (*2/*L) was associated with GC (OR = 2.942, 95%CI: 1.09-7.93).
2005	Mexico Garza-González et al[12]	63 distal GC; 215 non-cancer lesions	IL-1B-31T/C IL-1RN intron 2 VNTRTNF-α-308G/A	Presence of IL-1B-31*C allele was associated with increased risk of distal GC (OR = 7.631, 95%CI: 1.73-46.94)
2005	Brazil Rocha et al[73]	168 GC H. pylori +;541 asymptomatic controls	IL-1B-511C/T; -31T/CIL-1RN intron 2 VNTRTNF-α-308G/A	IL-1RN*2 was associated with noncardia GC (OR = 1.93, 95%CI: 1.06-3.49)
2006	Mexico Sicinschi et al[58]	183 GC; 377 controls	IL-1B-31T/C; +3954 C/TIL-10-592C/A IL-1RN intron 2 VNTR	IL-10-592*C allele carrier was associated with intestinal-type of GC (OR = 2.081, 95%CI: 1.07-4.05). Subjects with IL-1B-31 CC genotype and H. pylori CagA positive serology had an increased risk of intestinal-type GC (OR = 3.192, 95%CI: 1.05-9.68)
2006	HondurasMorgan et al[45]	170 GC; 162 healthy controls	IL-1B-511C/TIL-10-1082G/AIL-1RN intron 2 VNTRTNF-α-308 G/A	IL-1B-511 TT + IL-10-1082 AA combination increased risk of GC (OR = 2.6, 95%CI: 1.0-6.8)
2007	Costa Rica Con et al[43]	58 AG; 31 corpus AG; 23 IM	IL-1B-511C/T; +3954C/TIL-10-1082G/A; -592C/AIL-1RN intron 2 VNTR	IL-1B+3954*T carrier and IL-1RN homozygous *2 allele were associated with IM (OR = 3.41, 95%CI: 1.2-10.00 and OR = 3.12, 95%CI: 1.1-9.00, respectively)
2008	Costa Rica Sierra et al[42]	25 ABG; 76 AAG; 253 NAG; 21 Normal mucosa; 21 healthy controls	IL-1B+3954C/TIL-1RN intron 2 VNTR	No association was found
2009	Peru Gehmert et al[46]	133 GC vs 133 NAG86 NAG vs 43 ChrAG	IL-1B-511C/TIL-1RN intron 2 VNTR	IL-1B-511*C allele carrier and CT and CC genotypes were associated with AG (OR = 5.61, 95%CI: 2.02-15.51; OR = 4.82, 95%CI: 1.65-13.83; OR = 11.22, 95%CI: 2.27-55.37, respectively) and GC (OR = 2.361, 95%CI: 1.34-4.11; OR = 2.172, 95%CI: 1.23-3.84; OR = 4.152, 95%CI: 1.33-12.93, respectively)
2009	Brazil Melo Barbosa et al[74]	177 gastric benign pathologies; 100 asymptomatic controls	IL-1B-511C/T; -31T/C IL-1RN intron 2 VNTR TNF-α-308 G/A	Carriers of IL-1RN*2 allele with H. pylori CagA-positive serology had a greater risk of developing GU (OR = 8.82, 95%CI: 1.762-44.181) and GC (OR = 16.76, 95%CI: 1.99-140.71)
2009	Costa Rica Con et al[44]	52 GC; 191 non-cancer H. pylori positive patients	IL-1B-511C/T; +3954C/T IL-10-1082G/A; -592C/A IL-1RN intron 2 VNTR	IL-1B+3954 TC (OR = 2.12, 95%CI: 1.0-4.3), IL-1RN *2/*L (OR = 3.52, 95%CI: 1.7-7.3), IL-10-592 AA (OR = 3.12, 95%CI: 1.2-8.2) and IL-10-592 CA (OR = 3.22, 95%CI: 1.5-6.8) genotypes, as well the IL-1B+3954 TC, IL-1RN *2/*L, IL-10-592 CA (OR = 4.7, 95%CI: 1.7-13.0) combination were associated with GC
2009	Venezuela Cañas et al[84]	84 GC; 84 ChrG	IL-1B-511T/C; +3954C/TIL-10-592C/A IL-1RN intron 2 VNTR	IL-1B+3954*C carrier and IL-IRN *2/*2 genotype were associated with GC (OR = 6.21, 95%CI: 1.3-28.8 and OR = 7.02, 95%CI: 2.3-21.5, respectively). The IL-IRN *2/*2 genotype was also associated with a well/moderately-differentiated adenocarcinoma (OR = 8.12, 95%CI: 2.5-26.8)
2010	Mexico Martínez-Carrillo et al[56]	100 ChrG; 28 GU102 healthy controls	IL-1B-511C/T; -31T/C	The IL-1B-511 TC genotype and the -511*C allele were associated with ChrG (OR = 3.12, 95%CI: 1.4-6.8 and OR = 3.01, 95%CI: 1.4-6.3, respectively). The subjects carrying -31*T were found to be at a higher risk of having ChrG (OR = 2.81, 95%CI: 1.3-5.8). The IL-1B-511*C/-31*T haplotype was associated with ChrG (OR = 2.1, 95%CI: 1.2-3.8).
2010	Venezuela Chiurillo et al[85]	109 ChrG	IL-1B-511C/T; -31T/C; +3954C/T IL-1RN intron 2 VNTR	Carriage of IL-1B-511*T (OR = 5.4, 95%CI: 1.9–15.8) and -31*C (OR = 5.1, 95%CI: 1.8–14.7) alleles combined with iceA2+ H. pylori genotype increased the risk of ChrAG with severe histopathological changes.
2011	Colombia Martínez et al[88]	46 GC; 99 NAG	IL-1B-511C/T IL-1RN intron 2 VNTR	IL-1B-511 TT carriers had increased risk of GC (OR = 11.312, 95%CI: 1.20-106.54)
2011	Colombia Martínez et al[91]	58 GC; 89 DU (54 with precancerous lesions); 194 ChrG and normals	IL-1B-511C/T IL-1RN intron 2 VNTRIL-10-1082G/A; -819C/T;TNF-α-308G/A	Genotype IL-1B-511 TT was associated with GC (OR = 4.692, 95%CI: 1.22-18.09)
2011	Venezuela Chiurillo et al[86]	121 ChrG	IL-1B-511C/T; -31T/C; +3954C/T	There was association with severe histological changes only considering H. pylori genotypes
2012	Mexico López-Carrillo et al[57]	158 GC; 317 clinical controls	IL-1B-31T/C	IL-1B-31*C allele carriers who were both H. pylori CagA positive and with moderate to high Capsaicin consumption had increased risk of GC (OR = 3.411, 95%CI: 1.12-10.43)
2013	Brazil Mattar et al[94]	19 GC; 71 clinical controls; 196 inflammation of the upper gastrointestinal tract; 28 GU; 76 DU	IL-1RN intron 2 VNTR	The carriage of IL-1RN *2/*2 was an independent risk factor for GC (OR = 5.81, 95%CI: 1.06-31.98). The carriage of allele *2 had an independent protective effect on DU (OR = 0.45, 95%CI: 0.22-0.91)
2013	Brazil de Oliveira et al[79]	200 GC; 229 ChrG; 240 healthy individuals	IL-1RN intron 2 VNTR	Association with GC was observed for IL-1RN*2 (OR = 2.601, 95%CI: 1.65-4.10), TNF-α -857*T (OR = 1.701, 95%CI: 1.08-2.67), IL-8-845*C (OR = 3.461, 95 % CI: 1.69-7.07), IL-10-592*A (OR = 2.341, 95%CI: 1.47-3.70), TLR2 –196 to –174 *Del (OR = 2.201, 95%CI: 1.28-3.78) and TLR4+896*G (OR = 2.091, 95 % CI: 1.08-4.02) alleles. Association with ChrG was observed with IL-1RN*2 (OR = 1.881, 95%CI: 1.25-2.83) and IL-10-592*A (OR = 3.001, 95%CI: 1.99-4.50) alleles
			TNF-α-857C/T
			TNF-α-308G/A
			TNF-β-252G/A
			IL-8-251T/A
			IL-8-845T/C
			IL-10-592C/A
			TLR2–196 to –174 Ins/Del
			TLR4+896A/G (D299G); +1196C/T (T399I)

¹ Dominant;

² Co-dominant. H. pylori: Helicobacter pylori; GC: Gastric cancer; ChrG: Chronic gastritis; ChrAG: Chronic atrophic gastritis; DU: Duodenal ulcer; NAG: Non-atrophic gastritis; GU: Gastric ulcer; AAG: Atrophic antral gastritis; ABG: Atrophic body gastritis; IM: Intestinal metaplasia.