Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology -IDIBELL, Barcelona, Spain.Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology -IDIBELL, Barcelona, Spain.
A genome-wide study performed in a Japanese population identified a strong association between SNP rs2294008 (Met1Thr) in the Prostate Stem Cell Antigen gene (PSCA) and diffuse-type gastric cancer (GC). This association was validated in different Asian populations and very recently a study has been published in Caucasians. In this study we analyzed the association between PSCA variation and gastric cancer risk in Caucasians from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Six tagSNPs covering the PSCA gene region were genotyped in 411 incident gastric adenocarcinoma cases and 1530 matched controls from a nested case-control study in the EPIC cohort. Associations were analyzed by unconditional logistic regression, adjusting for age, sex and country. The T allele of rs2294008 in PSCA was found to be a highly significant risk factor for GC (per allele OR=1.42, 95%CI:1.23-1.66, p-value=6.5×10(-6) ), particularly of the noncardia-type (per allele OR=1.47, 95%CI:1.19-1.81, p-value=3×10(-4) ). At contrast with previous studies, no significant differences were observed between the diffuse (per allele OR=1.54, 95%CI:1.20-1.96, p-value=5×10(-4) ) and the intestinal (per allele OR=1.52, 95%CI:1.20-1.93, p-value=5×10(-4) ) GC histological subtypes. Although rs12155758 and rs9297976 were also found associated with GC, this association appeared to be due to LD with rs2294008. Haplotype analysis did not provide additional information. These results confirm the association between variation in the promoter region of PSCA and GC risk in Caucasians and also indicate that the rs2294008 variant is a similar risk factor for both the diffuse and intestinal-types of GC.
Sala N, Muñoz X, Travier N, Agudo A, Duell EJ, Moreno V, Overvad K, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Canzian F, Kaaks R, Boeing H, Meidtner K, Trichopoulos A, Tsiotas K, Zylis D, Vineis P, Panico S, Palli D, Krogh V, Tumino R, Lund E, Bueno-de-Mesquita HB, Numans ME, Peeters PH, Quirós JR, Sánchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Hallmans G, Stenling R, Manjer J, Allen NE, Travis RC, Khaw KT, Jenab M, Offerhaus GJ, Riboli E, González CA. Are you the author?
Reference: Int J Cancer. 2011 Jun 16. Epub ahead of print.