OGG1 S326C is a frequent genetic polymorphism, present in more than 20% of people of European and Asian descent (Janssen et al. 2001, Moritz et al. 2014). On its own, substitution of serine with cysteine at position 326 does not affect the catalytic activity of OGG1 (Dherin et al. 1999, Janssen et al. 2001, Moritz et al. 2014). However, under oxidative stress, OGG1 S326C variant is more susceptible to oxidation or nitrosation than the wild type enzyme (Moritz et al. 2014), which diminishes catalytic activity and leads to accumulation of genomic 8-oxoguanine (8oxoG) (Yamane et al. 2004, Moritz et al. 2014) under conditions of oxidative stress (Kershaw and Hodges 2012). This may be due to decreased specificity of OGG1 S326C for 8oxoG and FapyG (Dherin et al. 1999).
The frequency of OGG1 S326C allele is increased in NSCLC patients and the level of 8-oxodG is higher in lung tissue and leukocytes of these patients (Janik et al. 2011). OGG1 S326C variant is associated with an increased breast cancer risk (Ali et al. 2015).