Glucose-6-phosphate dehydrogenase deficiency and risk of colorectal cancer in Northern Sardinia A retrospective observational study

Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with a lower cancer risk, possibly via a reduction of
mutagenic oxygen-free radicals and by reducing nicotinamide–adeninedinucleotide–phosphate for replicating cells. In Sardinia, the
enzyme defect is frequent as a consequence of selection by malaria in the past. This study investigated the relationship between
G6PD deficiency and colorectal cancer (CRC).
A retrospective case-control study of 3901 patients from Sardinia, who underwent a colonoscopy between 2006 and 2016, was
performed. G6PD phenotype was assessed for each subject. The proportion of pre and malignant colorectal lesions was compared
in cases (G6PD-deficient) and controls (G6PD-normal). Data concerning age, sex, family history of CRC, smoking habits, body
height, and weight, and also associated diseases were collected.
The CRC risk reduction was 43.2% among G6PD-deficient compared with G6PD-normal subjects (odds ratio 0.57, 95%
confidence interval 0.37–0.87, P=0.010). Age, sex, family history of CRC, and also comorbidities such as type 1 diabetes and
ischemic heart disease, were significantly associated with CRC risk. The protective effect of G6PD deficiency remained significant
after adjusting for all covariates by logistic regression analysis, and was consistently lower across all age groups.
Glucose-6-phosphate dehydrogenase enzyme deficiency is associated with a reduced risk of CRC.