MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer.
Two common mutations, 677 C-->T and a1298 A-->C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors. Helicobacter pylori (HP) infection was also determined. An increased risk was found for 677TT in GC patients with respect to blood donors (odds ratio (OR) = 1.98), and statistical significance was sustained when we compared sex-age-matched GC patients and donors (OR = 2.37). The 677TT genotype association with GC was found in women (OR = 3.10), while a reduction in the 667C allele frequency was present in both the sex. No statistically significant association was detected when 677-1298 genotype was stratified by sex and age. Men of GC-relatives showed a higher 1298C allele frequency than donors (OR = 4.38). Between GC and GC-relatives, HP infection frequency was similar. In conclusion, overall findings support the hypothesis that folate plays a role in GC risk. GC-relatives evidence a similar 677TT frequency to that found in the general population.
Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Aviano, Italy. vdere@cro.it
Valli
V
De Re
R
R
Cannizzaro
V
V
Canzonieri
E
E
Cecchin
L
L
Caggiari
E
E
De Mattia
C
C
Pratesi
P
P
De Paoli
G
G
Toffoli
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics*
D042965:Methylenetetrahydrofolate Reductase (NADPH2)