Phylogenetic origin of Helicobacter pylori pathogenicity island and risk of stomach cancer and high-grade premalignant gastric lesions.

Infection by Helicobacter pylori (Hp) has been causally linked to risk of gastric cancer (GC). The coevolution of Hp and humans shaped the risk of GC as our species left Africa and migrated to the other continents. Latin America (LatAm) is a high GC incidence region where Hp evolved uniquely in the 500 years since European colonization. Differential virulence of the Hp cagA -pathogenicity island (cagPAI) by ancestral origin has been reported. We hypothesized that Hp phylogenetic origin might play a role in determining GC risk in LatAm. We used genotypes of 50 Hp genetic variants mapping to the Hp cagPAI, studied in 1220 subjects from Venezuela, Colombia, Mexico and Paraguay, who were infected with cagA-positive Hp, including 150 GC, 177 high-grade premalignant lesions (HGPMLs) and 893 low-grade premalignant lesions. We estimated the phylogenetic origin of Hp cagPAI in all study subjects by use of the STRUCTURE software and principal component analysis (PCA) and tested whether the estimated African ancestry percentage was associated with the risk of GC or HGPML. African ancestral component estimates by STRUCTURE and PCA were highly correlated. STRUCTURE-based African origin estimate was not significantly associated with the risk of HGPML, but it was inversely associated with GC risk: the OR associated with the continuous values of African component was 0.09 (95% CI, 0.01-0.85; P = 0.035). Similar trends were observed for GC with PCA-based estimates, but the association was not statistically significant. These results suggest that Hp ancestral origin may play a role in gastric carcinogenesis.

Asociación de los polimorfismos IL-1B-511 e IL-1RN y Helicobacter pylori CagA positivo con cáncer gástrico en una zona de riesgo alto en Colombia / Association of interleukin-1 genetic polymorphism and CagA positive Helicobacter pylori with gastric cancer in Colombia

Background: There is an association of interleukin (IL)1B polymorphism with gastric cancer risk. However systematic reviews of the existing evidence have shown that such association varies across populations with different genetic ancestry. Aim: To evaluate the association of IL-1B-511 and IL-1RN polymorphism and Helicobacter pylori IgG antibodies CagA, with gastric cancer in two Colombian cities located in a high risk area for gastric cancer. Material and Methods: A case-control study including 46 gastric cancer cases and 99 controls with non-atrophic gastritis from a high risk zone for gastric cancer. Polymorphism genotyping was carried out by polymerase chain reaction (PCR) and IgG CagA status by ELISA. Results: IgG CagA seropositive individuals had an increased gastric cancer risk (odds ratio (OR) = 11.56; 95 percent confidence intervals (CI) 2.62-50.91 in Tunja and OR = 19.66, 95 percentCI 0.98-395 in Bogotá). IL-1B-511TT carriers in Tunja had increased risk of gastric cancer (OR = 11.31; 95 percentCI 1.20-106.54)), while IL-1RN*2 alelle carriers in Bogotá showed an inverse association with gastric cancer risk (OR = 0.03; 95 percentCI 0.01-0.65). Conclusions: This study adds evidence to the positive association of Helicobacter pylori CagA positive strains with non-cardial gastric cancer etiology. There is a possible heterogeneity in the association of IL-1B gene polymorphism with cancer, in populations of similar ethnic background and settled in the same risk area.

A non-radioactive PCR-SSCP analysis allows to distinguish between HPV 16 European and Asian-American variants in squamous cell carcinomas of the uterine cervix in Colombia.

UNLABELLED: Human Papillomavirus type 16 (HPV 16) DNA is regularly found in around 50% of all cervical carcinomas. Variants of this type have been found associated with different risks for cervical cancer development. Presence of HPV 16 variants in Colombia has not been previously reported. The aims of this study were to assess the feasibility of non-radioactive PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) analysis for determination of variability of ORF of E6, variability in the enhancer sequence of the LCR, and for establishment of the distribution of HPV 16 variants in invasive squamous cell carcinoma of the uterine cervix in Colombian women. Biopsies from 59 patients at the Instituto Nacional de Cancerología (INC) in Bogotá (Colombia) were collected. HPV detection was performed using universal primers. HPV 16 variants were detected by non-radioactive single-stranded conformational polymorphism (SSCP) analysis and direct sequencing. HPV 16 was detected in 57.6% of the tumors. The European branch was identified in 88.2% of the samples with the E-G350 class being the most prevalent variant (41.1%). The Asian-American branch was identified in 8.8% of the samples. Within this group it was possible to distinguish between c and a classes. It was not possible to determine the branch in 2.9% of the cases. A nucleotide transition (G to A) at position 7521 was the most prevalent variation (80%) found in the enhancer sequence of the LCR region. CONCLUSION: A non-radioactive PCR-SSCP analysis allowed us to distinguish between European and Asian-American branches of HPV 16, and to distinguish among classes in squamous cell carcinomas of the uterine cervix in Colombia. This method is an excellent alternative that can be used as a screening tool for identification of HPV 16 variants.