Genetic and Environmental factors driving Lung Cancer Rates in Atlantic Canada

Aim/goals:

  1. To evaluate environmental factors that contribute to lung cancer (LC) in Atlantic Canada

  2. To uncover germline variants and genetic mutation signatures underlying LC in AC and lung cancer multiple primary (LCMP) tumors using whole-genome sequencing (WGS)

  3. To compare the genetic mutational profiles from Aim 2 with changes in the total transcriptome in these cancers from individuals with and without identified germline cancer predisposition variants as well as those with high vs low levels of environmental risk factor exposure (i.e. radon, uranium, thorium, arsenic). 

Summary:

In Canada, one in every five cases of lung cancer is diagnosed in people who have never smoked. This suggests that the causes of lung cancer are not only related to smoking, but to other environmental factors as well. The main environmental causes of lung cancer in non-smokers are radon, arsenic, and other environmental carcinogens. Radon is a gas that builds up in sealed areas, such as newer buildings, and damages DNA with radiation. Arsenic, a metalloid, can get into food and water supplies, and damage cells through chemical reactions. Air pollution and other forms of radiation can also contribute to lung cancer in people who do not smoke. In Atlantic Canada, the rate of lung cancer is around 30% higher than in other provinces. Environmental factors (such as radon, arsenic, and air pollution) are thought to be the cause of this high rate. The unique genetic structure of the population in Atlantic Canada could also make some individuals more likely to be affected by environmental carcinogens. Interestingly, more than 10% of cases of lung cancer in Nova Scotia present with additional primary tumors in organs that are known targets of environmental carcinogens linked to lung cancer (such as arsenic).

We hypothesize that the combination of environmental exposure and genetic factors in Atlantic Canada is associated with the high rate of lung cancer. This exposure could also explain the emergence of a cohort of lung cancer patients with multiple primary cancers (LCMP) of different tissue origins, and the clustering of lung cancer in certain families in this region. We will measure exposure to residential radon in AC, estimate exposure to arsenic, air pollution and other elements using geographical province-wide mapping, and determine the amount of arsenic and other metals present in lung tissue from the Nova Scotia Lung Tumour Bank using a technology called inductively coupled plasma mass spectrometry (ICP- MS), which measures the amount of metals present in a sample. We will use DNA and RNA sequencing of the tumors analyzed to investigate how genetic and epigenetic variations are related to levels of environmental exposure. 

Key Researchers