Colorectal cancer mortality in relation to glucose-6-phosphate dehydrogenase deficiency and consanguinity in Sardinia: A spatial correlation analysis

Background: 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 homozygosity has been postulated. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been hypothesized to decrease CRC risk. In Sardinians, this disorder has a frequency of 12-24% due to selection by past malaria. In this study the relationship between mortality for CRC, homozygosity and G6PD deficiency was analysed using spatial analysis. Methods: The spatial association between CRC mortality and G6PD deficiency and homozygosity was assessed in the 377 municipalities of the island using ordinary least squares regression and geographically weighted regression. Results: 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 were observed on the south-western side of Sardinia. Conclusions: These results indicate that G6PD deficiency might contribute to reduce colon carcinogenesis, and is in line with in vitro and in vivo studies.