Healthy Lifestyle May Help Mitigate High Genetic Risk of Cancer
By
Journal in Which the Study was Published: Cancer Research, a
journal of the American Association for Cancer Research. Author: Guangfu
Jin, PhD, a professor at Nanjing Medical University.
Background: As genetic research continues to uncover loci, or
areas in DNA, with specific changes
that influence cancer risk, researchers can define polygenic risk scores
(PRS)—personalized estimates of an individual’s cancer risk—based on a
patient’s unique combination of these changes. However, most PRS are generated
for a specific cancer type, rather than for overall cancer risk.
“A PRS indicating risk of a certain cancer is important but not enough,” Jin said. “We tried to create an indicator—the cancer polygenic risk score (CPRS)—to measure the genetic risk of cancer as a whole.”
How the Study Was Conducted: Jin and
colleagues calculated individual PRS for 16 cancers in men and 18 cancers in
women, using available data from genome-wide association studies. They then
used statistical methods to combine these scores into a single measure of
cancer risk, based on the relative proportion of each cancer type in the
general population. Separate CPRS were generated for men and women.
To validate their CPRS, the researchers
utilized genotype information from 202,842 men and 239,659 women from
the UK Biobank, a cohort of general-population participants recruited from
England, Scotland, and Wales between 2006 and 2009, and calculated a CPRS for
each individual.
UK Biobank participants were surveyed
upon enrollment for various lifestyle factors, including smoking and alcohol
consumption, body mass index, exercise habits, and typical diet. Based on these
factors, Jin and colleagues classified each patient as having an unfavorable
(zero to one healthy factors), intermediate (two to three healthy factors), or
favorable (four to five healthy factors) overall lifestyle.
Results: Patients with the highest quintile
CPRS were nearly twice as likely (for men) and 1.6 times as likely (for women)
to have a cancer diagnosis by their most recent follow-up, in 2015 or 2016.
Notably, 97 percent of patients in the study had a high genetic risk (top
quintile) of at least one cancer type. “This suggests that almost everyone is
susceptible to at least one type of cancer,” Jin said. “It further indicates
the importance of adherence to a healthy lifestyle for everyone.”
Patients with an unfavorable lifestyle
and the highest quintile genetic risk were 2.99 times (in men) and 2.38 times
(in women) more likely to develop cancer than those with a favorable lifestyle
and the lowest quintile of genetic risk.
Among patients with high genetic risk,
the five-year cancer incidence was 7.23 percent in men and 5.77 percent in
women with an unfavorable lifestyle, compared with 5.51 percent in men and 3.69
percent in women with a favorable lifestyle. The decreased percentages are
comparable to the cancer risk in individuals with intermediate genetic risk,
Jin said. Similar trends were observed in all genetic risk categories,
suggesting that patients could benefit from a healthy lifestyle regardless of
genetic risk.
Author’s Comments: “Our findings indicate that
everyone should have a healthy lifestyle to decrease overall cancer risk,” Jin
said. “This is particularly important for individuals with a high genetic risk
of cancer. We hope our CPRS could be useful to improve a person’s awareness of
their inherited susceptibility of cancer as a whole and facilitate them to
participate in healthy activities.”
Study Limitations: Limitations of this study include
the fact that only the strongest genetic risk loci were included in the
individual PRS, which disregards the influence of loci with weaker effects.
Researchers also noted an imbalance in the number of loci included between
different cancer types, which can potentially skew their individual impact.
Reference: 28 July 2021, Cancer Research.
DOI: 10.1158/0008-5472.CAN-21-0836
Funding & Disclosures: This study was funded by the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, the National Key Research and Development Program of China, the High-Level Talents Cultivation Project of Jiangsu Province, the CAMS Innovation Fund for Medical Sciences, and the National Science Foundation for Postdoctoral Scientists of China. The authors declare no conflicts of interest.