In May, a 7-year study on mutagenic exposures in kidney cancer genomes was published in the journal ‘Nature‘. The study was conducted by an international scientific team and included authors such as Prof. Sonata Jarmalaitė and Dr. Rasa Sabaliauskaitė from the Life Sciences Center of Vilnius University and the National Cancer Institute. Nearly 1,000 kidney cancer genome sequences were analyzed, and specific mutation profiles related to the causes of the disease were identified. The study confirmed that smoking, intracellular processes, and exposure to aristolochic acid are the main triggers of kidney cancer. Additionally, a new and unique mutation profile was discovered.
The variation of mutagenic exposures in kidney cancer genomes cannot solely be explained by widely known cancer risk factors. The study aimed to identify previously unknown risk factors leading to kidney cancer by using a unique mutagenic algorithm that can identify carcinogens based on their mutation profile.
Samples of kidney cancer tumors from 1,000 individuals collected on five continents, including both high- and low-incidence regions, were analyzed. Lithuania, with the highest incidence rates of kidney cancer in Europe and the world, was one of the main targets of the study. A dominant type of mutation labeled SBS40 has been identified in the kidney cancer genomes from Lithuania and the Czech Republic, but the origin of this mysterious mutation remains unknown.
In the Balkan region, the high incidence of kidney cancer has been attributed to exposure to aristolochic acid, found in traditional medicines and associated with a specific mutation profile of kidney cancer. The study did not find a link between the mutation profile and obesity or hypertension, although they are known as common risk factors for kidney cancer.
Cancer develops due to the accumulation of genetic mutations caused by internal cellular processes, e.g. inaccurate DNA replication and repair, or by external environmental or lifestyle factors, such as ultraviolet radiation from sun exposure or harmful compounds in cigarette smoke.
‘Each tumor has a unique DNA mutation profile. A wealth of information on the mutation profiles of thousands of tumors has already been collected. The organized data can also be used to create a snapshot of mutational cancer – this kind of photograph is known as mutograph. It can reflect biological processes, the effects of carcinogens, regional patterns, and so on’, says Prof. Jarmalaitė, one of the researchers in this study.
The study involved collecting clinical samples from patients and completing questionnaires on health indicators and lifestyle habits. The tumor and leukocyte samples were sequenced at the Sanger Institute in Cambridge. Despite delays caused by the COVID-19 pandemic, the results of genome sequencing studies on 16 kidney tumor samples collected in Lithuania were published in the scientific journal ‘Nature’. The remaining samples will be used for further research.
Cancer mutagenesis research will continue through the ‘PROMINENT’ project, conducted by Cancer Research UK, which will focus on the early stages of carcinogenesis. The study aims to identify the cause of the dominant SBS40 mutation type in Lithuania and to take preventive measures to reduce the incidence of kidney cancer.
