Colorectal Cancer Mortality in Relation to Glucose‒6‒Phosphate Dehydrogenase Deficiency and Consanguinity in Sardinia: A Spatial Correlation Analysis

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Colorectal cancer (CRC) is one of the most diffuse malignancy in the world. In Southern Europe, the incidence and prevalence are lower than in most Western countries, although some hot spots of increased risk are emerging. In Sardinia, the cancer rate has risen steeply in the last years. Among risk factors for CRC, genomic </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">homozygosity has been postulated. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been hypothesized to </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">decrease CRC risk. In Sardinians, this disorder has a frequency of 12-24% due to selection by past malaria. In this study </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">the relationship between mortality for CRC, homozygosity and G6PD deficiency was analysed using spatial analysis. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">The spatial association between CRC mortality and G6PD deficiency and homozygosity was assessed in the </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">377 municipalities of the island using ordinary least squares regression and geographically weighted regression. Results: </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">A consanguinity index, available across all municipalities, was used as a proxy for homozygosity. A significant inverse correlation was found between CRC mortality and G6PD deficiency (ρ = ‒0.216; p = 0.002) whereas no association was found for consanguinity (ρ = ‒0.077; p = 0.498). The geographical map of CRC mortality showed a significant clustering in mountain areas compared to the population living in lowlands, whereas hot spot areas of G6PD deficiency </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">were observed on the south-western side of Sardinia. </span></span><strong><span style="font-size: small;">Conclusions: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">These results indicate that G6PD deficiency might </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">contribute to reduce colon carcinogenesis, and is in line with in vitro and in vivo studies. </span></span>