Various environmentalfactors play a role in disease development as a whole including obesity,smoking, drinking, and a poor diet.63, , -66 A retrospective study by Kim et al has shown that womennot only have a higher incidence of diffuse type GC but have a worse overallprognosis as well as genetic differences compared to men including ER-b expression67 suggesting a hormonal component may also be a contributing factor to thissubset of disease. This evidence concerns the gene ESR2 and obesity due to melanocortin 4 receptor deficiency.