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August 24, 2021
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National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, National Key Research and Development Program of China, High-Level Talents Cultivation Project of Jiangsu Province, CAMS Innovation Fund for Medical Sciences and National Science Foundation for Post-doctoral Scientists of China supported the study. The authors report no relevant financial disclosures.
A healthy lifestyle can reduce overall cancer incidence even among individuals identified by a personalized indicator as having a high genetic risk, according to study results published in Cancer Research.
“Polygenic risk scores measure individuals’ genetic predisposition to a specific cancer type and have been shown in previous studies to predict incidence of site-specific cancer. In our current study, we were very curious about how to measure overall genetic cancer risk for individuals,” Guangfu Jin, PhD, professor in the department of epidemiology at Nanjing Medical University in China, told Healio. “Thus, we created an indicator — dubbed cancer polygenic risk score — to measure overall genetic risk for all cancer types. In addition, we evaluated the extent to which a high genetic risk for overall cancer can be offset by a healthy lifestyle.”
Jin and colleagues pooled data on 442,501 individuals included in genome-wide association studies. They calculated individual polygenic risk scores for 16 cancer types in men and 18 cancer types in women, combined the scores into a single measure of cancer risk and generated separate cancer polygenic risk scores for men and women.
The investigators classified lifestyles as unfavorable, intermediate or favorable based on smoking status, alcohol consumption, physical activity, BMI and diet.
Results showed men in the highest quintile of cancer polygenic risk score were nearly twice as likely as those in the lowest quintile of risk to be diagnosed with cancer at their most recent follow-up in 2015 or 2016. Women in the highest quintile were 1.6 times as likely as those in the lowest quintile to be diagnosed with cancer.
“In addition, more than 97% of individuals had a high genetic risk for at least one cancer type, though this was defined by top-quintile genetic risk for a particular cancer,” Jin said.
The HR for overall cancer risk among men was 1.27 (95% CI, 1.21-1.34) for those with intermediate genetic risk vs. low risk and 1.91 (95% CI, 1.81-2.02) for those with high risk vs. low risk. Researchers observed a similar trend among women (HR for intermediate vs. low risk = 1.21; 95% CI, 1.16-1.27; HR for high vs. low risk = 1.62; 95% CI, 1.54-1.71).
Compared with people who had low genetic risk and a favorable lifestyle, the HR for those with high genetic risk and an unfavorable lifestyle was 2.99 (95% CI, 2.45-3.64) for men and 2.38 (95% CI, 2.05-2.76) for women.
Five-year standardized cancer incidence for individuals with high genetic risk but favorable lifestyles decreased from 7.23% to 5.51% among men and from 5.77% to 3.69% among women.
“Even though pan-cancer polygenic risk score analyses have been performed by other researchers, they usually focused on the predictive effect of site-specific cancer across multiple cancer types, instead of trying to construct an indicator that reflects the genetic risk for overall cancer,” Jin said. “To our knowledge, the present study is the first to provide convincing evidence that cancer polygenic risk scores can be used to assess the level of genetic risk on overall incident cancer risk.”
Although the study included U.K. Biobank participants with diverse ethnic backgrounds, the generalizability of the findings should be further assessed in non-European populations when available, Jin added.
“We are planning to construct an effective genetic indicator for overall cancer in diverse populations, such as the Chinese population” Jin said. “In addition, it is also important to evaluate the relationship of overall genetic risk for cancer in other ways, such as screening, therapy and prognosis.”
For more information:
Guangfu Jin, PhD, can be reached at The Affiliated Cancer Hospital of Nanjing Medical University, 101 Longmian Road, Nanjing 211166, China; email: [email protected].