1. Galamba, Elizabeth Rose

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When debating the phenomena of individual personality formation, the question of nature versus nurture is bound to be applied-the same could be said of the cancer debate. In a recent study, researchers constructed a new indicator, the cancer polygenic risk score (CPRS), that determines a person's risk for overall cancer, using the nature of that individual's genetics and the way in which they nurture their body (Cancer Res 2021; doi: 10.1158/0008-5472.CAN-21-0836).

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"Although numerous genetic loci used for CPRS have been identified in previous studies, we did not know how to utilize these loci to measure individuals' overall cancer risk," noted by Guangfu Jin, PhD, Professor at Nanjing Medical University in China.


Prior to the commencement of this study, polygenic risk scores (PRSs) were determined to be an effective method for identifying a patient's genetic risk for developing site-specific cancers, such as those of the breasts and stomach. However, PRSs were ineffective at identifying a person's risk for developing cancer overall, rather than individually.


In order to fill this void, researchers gathered data from the UK Biobank (UKB), procuring 20 PRSs for different types of site-specific cancers-excluding non-melanoma skin cancer and other cancers without applicable genome-wide association studies. The UKB was an extraordinary tool in identifying the significant genetic loci needed to construct the aforementioned PRSs.


With approximately 500,000 persons participating across England, Scotland and Wales, from the 2006 and 2010 baselines, the UKB collects extensive information on all participants through the use of questionnaires, interviews, and bodily measurements to collect data on participants' lifestyle choices. Blood samples are also taken for genotyping, using the UK BiLEVE Axiom or the UK Biobank Axiom Array. These systems were found to share more than 95 percent of single nucleotide polymorphisms (SNPs).


Now that data has been collected and PRSs have been identified for 20 different types of cancer, researchers constructed the new sex-specific CPRS formula:



Equation (Uncited) - Click to enlarge in new windowEquation (Uncited)

Here, CPRSi, or the cancer polygenic risk score of the ith individual, is found by using hk, the age-standardized incidence of site-specific cancer k, and PRSi.k, the polygenic risk score of site-specific cancer type k.


"First of all, we believe that in the future, a DNA-ID may be feasible for humans, which can be used for disease risk prediction, personalized screening, and precise therapy. A PRS indicating a certain cancer risk is important, but not enough, because we need to know the disease-related significance of genome better and better. Therefore, an indicator to measure the genetic risk for overall cancer is needed," Jin said.


Using the newly formulated CPRS indicator, researchers were able to place participants into three categories: 1) low genetic risk for overall cancer or the bottom quintile of CPRS, 2) intermediate genetic risk or quintiles 2 to 4 of the CPRS model, and finally, 3) high genetic risk or the top quintile. Hazard ratios were observed for men and women.


Men with a low genetic risk for developing cancer at baseline were found to have 19.72 percent absolute cumulative risk by age 75. Men with an intermediate risk of 25.10 percent and with a high risk of 38.32 percent. Women with a low genetic risk for developing cancer at baseline were found to have 15.83 percent absolute cumulative risk by age 75. Women with an intermediate risk of 20.86 percent and with a high risk of 29.17 percent. Yet, when factoring in complete follow-ups (October 31, 2015 in Scotland and March 31, 2016 in England and Wales) and lifestyle choices, these rates change significantly.


Similar to how participants were divided into categories based on their genetic risk, participants were placed on a lifestyle index (from 0-5, 5 indicating the healthiest lifestyle) based on their lifestyle choices. In this study researchers identified a total of five lifestyle choices that could affect a person's risk for developing cancer:


1. no current smoking (never smoked or hasn't smoked in at least 30 years);


2. no alcohol consumption (never consumed alcohol),


3. regular physical activity (at least 75 minutes of rigorous activity or 150 minutes of moderate activity per week),


4. a moderate body mass index (BMI, 18.5~30) and


5. a healthy diet pattern (more fruits and vegetables, less processed and red meats).



At baseline, most participants were found to have fallen into 2-3 of these lifestyle choices.


"Other factors such as air pollution, occupational exposures (such as radiation and metal exposure, etc.), and infectious factors (such as H. pylori, HBV, HCV, EBV, etc.) that are partly related to an individual's lifestyle also contribute to cancer," Jin said, although these factors are not considered in the study.


For men and women living with high genetic risk and unfavorable lifestyle choices, their 5-year incident cancer rates were found to be 7.23 percent and 5.77 percent, respectively. In comparison to the rates of men (5.51%) and women (3.69%) with a high genetic risk and favorable lifestyle choice, those men and women living unfavorable lifestyles are at a significantly greater risk to develop cancer. The same could be said for persons with a low genetic risk. For men and women with a low genetic risk and unfavorable lifestyle the rates were observed at 4.14 percent and 3.42 percent, respectively. Whereas the rates observed for persons with a low genetic risk and favorable lifestyle rest at 2.24 percent for men and 2.53 percent for women.


"We encourage everyone to adopt a healthy lifestyle to reduce his/her overall cancer risk. Actually, this is impossible, and the compliance is usually low. Nevertheless, individuals in high genetic risk will take actions to reduce their cancer risk, especially in the future, when genome sequencing is accessible for everyone, and the genetic risk can be easily known," Jin noted. "Therefore, we hope our CPRSs could be useful to improve a person's awareness of their inherited susceptibility to cancer as a whole and facilitate them to participate in precision medical activities."


There are several limitations to this study that could possibly affect the accuracy of the study's results. For example, the participants' lifestyle choices were self-reported, which could present a possible miscalculation in risk levels. Yet, it is clear from the reported 5-year incident cancer rates that the adoption of a healthy lifestyle can offset a person's risk for developing cancer.


Elizabeth Rose Galamba is a contributing writer.