Smoking and Infectious Diseases
“Our individual life history is inscribed in our epigenome,” states Toshikazu Ushijima, Ph.D., chief of the carcinogenesis division at the National Cancer Center Research Institute, Tokyo. Dr. Ushijima and collaborators screened genes that were silenced in esophageal squamous cell carcinomas and demonstrated that methylation levels in five promoters are significantly correlated with the duration of tobacco smoking, indicating that chronic smoking induces methylation changes in many of these genes.
This finding supports the idea that smoking induces an epigenetic field of cancerization, a term that was previously described for breast, colon, liver, and stomach cancers, and is used to denote epigenetic modifications that occur during the early stages of carcinogenesis.
Back in 2006, Dr. Ushijima and colleagues used real-time methylation-specific quantitative PCR to conduct a temporal characterization of DNA-methylation levels in the gastric mucosa in patients infected with Helicobacter pylori, a pathogen that represents a major cause of gastric cancer in several countries worldwide.
The investigators revealed that methylation of promoter CpG islands was high in individuals infected with Helicobacter pylori, and that high methylation levels correlated with the subsequent risk to develop gastric cancer. This pointed toward an epigenetic field for cancerization established as a result of the infection and measurable by DNA-methylation levels. Methylation levels decreased after the bacteria were eradicated but were still much higher as compared to individuals without the infection during their lifetime. “The epigenetic field defects are becoming more and more important,” says Dr. Ushijima.
Increasingly, new revelations about epigenetic modifications promise to transform all facets of cancer biology and to provide prophylactic, diagnostic, and therapeutic benefits. Epigenetic modifications could, in addition, become one of the missing links between infectious diseases and cancer.
The ability of certain viruses, bacteria, parasites, and protozoa to cause malignant transformation represents one of the most fascinating topics in life sciences. This connection was regularly re-discovered throughout the past century, it repeatedly fell into oblivion and, historically, demonstrating causality often proved challenging.
It is currently estimated that approximately 20% of all cancers worldwide are linked to pathogens, and the involvement of epigenetic changes in shaping this connection could soon lead to new chapters in cancer biology, establishing links that we never would have thought could exist.