How the environment shapes cancer genomes.

OBJECTIVE

The mutational patterns of cancer genomes allow conclusions or generation of hypotheses as to what mechanisms or environmental, dietary or occupational exposures might have created the mutations and therefore will have contributed to the formation of the cancer. The arguments for cancer causation are particularly convincing when epidemiological evidence can support the theory that a particular exposure is linked to the cancer and when the mutational process can be recapitulated in experimental systems. In this review, I will summarize recent evidence from cancer genome sequencing studies to exemplify how the environment can modulate tumor genomes.

RESULTS

Mutation data from cancer genomes clearly implicate the ultraviolet B component of sunlight in melanoma skin cancers, tobacco carcinogen-induced DNA damage in lung cancers and aristolochic acid, a chemical compound found in certain herbal medicines, in urothelial carcinomas of exposed populations. However, large-scale sequencing is beginning to unveil other unique mutational spectra in particular cancers, such as A-to-C mutations at 5'AA dinucleotides in esophageal adenocarcinomas and complex mutational patterns in liver cancer. These datasets can form the basis for future studies aimed at identifying the carcinogens at work.

CONCLUSIONS

The findings have substantial implications for our understanding of cancer causation and cancer prevention.