Genetic Risk for Overall Cancer and the Benefit of Adherence to a Healthy Lifestyle: A review

This post is a review on a paper in American Association of Cancer Research, which describes association of PRS and lifestyle with developement of 20 types of cancer.

Genetic Risk for Overall Cancer and the Benefit of Adherence to a Healthy Lifestyle

Methods

First, this paper performs a systematic review on GWAS, just like work in our lab so far. It searches for SNPs associated with 20 different cancers. Interestingly, they combine them all into a single PRS for overall cancer. This was performed by creating a PRS for each of the 20 cancer types, then multiplying it by the overall cancer incidence in the UK, and then summing it with the other cancer-specific PRS.

The SNPs were chosen if GWAS showed P value < 5x10-8 and underwent all the standard LD pruning and quality control.

Each of the individual cancer-specific PRSs were also sex-specific and built using SNPs and their respective SNP weighting, with adjustments for age, family history of cancer, Townsend deprivation index, height, and the first 10 principal components of ancestry.

The study also evaluated for lifestyle factors, which included the following: no current smoking, no alcohol consumption, regular physical activity, moderate BMI, and a healthy diet pattern.

Next, the PRS are applied to the UK biobank and PRS scores across quintile were compared with true cancer risk. The interactions between lifestyle and cancer risk were also evaluated.

Results

Results of the application of PRS to cancer risk in men and women are shown below.

They also assessed the impact of lifestyle factors.

Of interest, this paper shows another example of what happens when lung cancer risk was assessed through PRS. This study only identified 17 SNPs to be included in lung cancer risk because they used a much higher cutoff for SNP selection (p value < 5x10e8). The result for lung cancer PRS was very weak. The odds ratio in men was 1.17 sd 1.12-1.26, which had p value 8.48E-09. It’s also interesting to note that I do not know how much of this statistically significant odds ratio was produced by controlling variables such as age and principal components.

The specific graph and results from the lung PRS using 17 SNPs is below:

Conclusion and Discussion

Genetic risk and healthy lifestyle act in concert to influence incident cancer risk. These PRS could potentially impact a patient’s awareness of their inherited susceptibility to cancer and encourage them to improve lifestyle and participate in cancer prevention programs.

Lastly, the evaluation of 17 SNPs associated with lung cancer in PRS on the UK biobank was stastitically significant but not impressive when compared to more strongly linked genetic cancers such as breast cancer and prostate cancer.