ABSTRACT
Serologic screening of gastric cancer [GC] by serum pepsinogens [sPG] levels and Helicobacter pylori [Hp] sero-status, though highly informative, has provided heterogeneous results. Here, we have evaluated the modifying effects of demographic factors on the risk impact of Hp sero-status/sPG levels in gastric cancer, with particular emphasis on age. A cross-sectional study was carried out on 1341 individuals [GC = 578, healthy = 763], who were stratified into two age groups: 35-59 years [middle-aged, n = 830] and >/= 60 years [60 years-plus, n = 511]. Demographic factors and serological states [Hp sero-staus and sPG levels] were recorded by subject interview and serum ELISAs, respectively. Covariate-specific odds ratios were calculated by multivariable logistic regression. Hp infection was consistently associated with increased sPGI and sPGII levels in the 60 year-plus, but not the middle-aged group. The joint examination of the variable states of the three serum biomarkers [Hp serology, sPGI, and sPGI/II ratio], in the 60 year-plus age group, demonstrated a stepwise escalation of risk from the single [sPGI[low]; OR = 2.6], to double [sPGI[low]/sPGI/II[low]; OR = 3.55, and Hp[positive]/sPGI[low]; OR = 5.0] and ultimately triple [Hp[positive]/PGI[low]/PGI/II[low]; OR = 10.48] positive states, in reference to the triple negatives. However, this pattern was not exhibited in the middle-aged subjects. Age was clearly identified as a modifying factor on the risk projection of the combined states of Hp serology and sPG levels in gastric cancer screening, reflected by the augmented [tilde10.5 fold] risk of GC in the triple positive [Hp[positive]/sPGI[low]/sPGI/II[low]] 60 year-plus subjects, which was not evident in the middle-aged group
ABSTRACT
Attempts for early detection of gastric cancer have recently focused on host's genetic susceptibility factors and gene-environment interactions. We have, herein, studied the association of MTHFR C677T single nucleotide polymorphism [SNP] and its interaction with Helicobacter pylori infection, smoking, age and gender on the risk of gastric cancer among an Iranian population. Gastric cancer patients [n = 450] and cancer-free controls [n = 780] were studied for serum H. pylori-specific IgG antibodies by ELISA and MTHFR C677T polymorphism [SNP] by PCR-RFLP. Demographic and life style data were collected through patient interviews. Unconditional logistic regression model estimated odds ratio [OR] and the corresponding 95% confidence intervals [CI]. The interactions of MTHFR genotype with H. pylori infection [P = 0.03], age [P = 0.049] and gender [P = 0.007] were statistically significant. Accordingly, MTHFR C677T carriers who were also positive for H. pylori infection exhibited 80% [OR = 1.8, 95% CI = 1.0-2.9] significant excess risk of non-cardia gastric cancer. Furthermore, subjects over the age of 50 or female subjects carrying MTHFR C677T SNP showed 40 [OR = 1.4, 95% CI = 1.0-2.0] and 100 [OR = 2.0, 95% CI = 1.2-3.2] percent increased risk of gastric cancer, respectively. MTHFR C677T SNP seems to increase the risk of gastric cancer and the effect is significantly inflated by interactions with H. pylori infection, age and gender