Gene Variant Linked to Risk of Oral Squamous Cell Carcinoma

The presence of a MTHFR C677T single-nucleotide polymorphism is significantly associated with an increased risk of oral squamous cell carcinoma, suggests a meta-analysis published in PLOS One.

Another MTHFR single-nucleotide polymorphism (SNP), A1298C, did not appear to be associated with oral squamous cell carcinoma.

“Individuals carrying the ‘T’ allele [of C677T] had a nearly 43% increased risk for oral squamous cell carcinoma development,” reported researchers at the Jinan Stomatological Hospital in Shandong, China.

The authors pooled data from 13 studies, representing 1,539 patients, for analysis. Previous research has demonstrated that epigenetic methylation of the MTHFR gene, which can modulate its expression, contributes to human papillomavirus (HPV)-positive cervical cancer, the authors noted.

The possible association between MTHFR C677T and oral cancers has been controversial, according to Teodoro Bottiglieri, PhD, program director at the Center for Metabolomics of the Baylor Institute of Metabolic Disease at the Baylor Scott & White Research Institute in Dallas.

“Earlier research had suggested this SNP might be associated with an overall decrease in the risk of all types of oral cancers taken together,” Bottiglieri told Cancer Network. “But oral squamous cell carcinoma is the most common and most aggressive oral cancer, with a high 5-year mortality rate, so it was justified to go back and select only those studies for analysis,” he said.

The studies included in the meta-analysis did not consistently report tobacco use, alcohol use, or HPV infection status among patients. The authors were therefore unable to control for these risk factors in their statistical analysis, Bottiglieri cautioned.

“[The researchers] didn’t have access to confounding variables like age, smoking status, or viral infection,” he explained. “Smoking causes inflammation and increases the risk of periodontal disease, which in turn increases the risk of oral cancers. That’s an important risk factor they didn’t account for. And in four of the included studies, they didn’t have pathological confirmation of oral squamous cell carcinoma,” Bottiglieri told Cancer Network.

Diet can also dramatically modulate the impact of MTHFR gene polymorphisms.

“Some of the effects of this mutation can be overridden by diet, by increased intake of folate in the diet,” said Bottiglieri. “Folate deficiency leads to DNA strand breaks. There’s a good rationale for studying these polymorphisms and C677T in particular, because it’s quite prevalent in the population-10%–12% of Caucasians, and as high as 24% in Hispanic and Mediterranean populations.”