Studies show that unhealthy lifestyles—including smoking, drinking alcohol, having obesity, being physically inactive, and eating a poor diet—are associated with an increased risk of developing cancer. Studies also show that practicing a healthy lifestyle is associated with an increase in total life expectancy and a life expectancy free of cancer, as well as other life-threatening diseases, including heart disease and type 2 diabetes.

A new study published by Zhu et al in Cancer Research found that refraining from smoking and drinking as well as maintaining a healthy weight, diet, and regular physical activity may help to mitigate cancer incidence, even in individuals at high risk for the disease.

Study Methodology

The researchers constructed an incidence-weighted cancer polygenic risk score (CPRS) for overall cancer risk derived from 16 cancer sites in men and 18 cancer sites in women, using available data from genome-wide association studies. They then used statistical methods in the general population. Separate CPRSs were generated for men and women.

To validate their CPRS, the researchers used 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 2008 and 2009, and calculated a CPRS for each individual. The UK Biobank participants were asked upon enrollment about their smoking and alcohol consumption, body mass index, exercise habits, and diet. Based on these factors, the researchers 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.

The researchers also assessed the utility of the CPRS over the life course and estimated the extent to which a healthy lifestyle was associated with a reduced overall cancer risk across groups with a different genetic risk defined by CPRS.

Cox regression by sex was used to analyze associations of genetic and lifestyle factors with cancer incidence using the UK Biobank data.

Key Results

The researchers found that compared with participants at low genetic risk (bottom quintile of CPRS), those at intermediate (quintiles 2 to 4) or high (top quintile) genetic risk had hazard ratios of 1.27 (95% confidence interval [CI] = 1.21–1.34) or 1.91 (95% CI = 1.81–2.02) for overall cancer, respectively, for men, and 1.21 (95% CI = 1.16–1.27) or 1.62 (95% CI = 1.54–1.71), respectively, for women. A joint effect of genetic and lifestyle factors on overall cancer risk was observed, with hazard ratios reaching 2.99 (95% CI = 2.45–3.64) for men and 2.38 (95% CI = 2.05–2.76) for women with high genetic risk and unfavorable lifestyle compared with those with low genetic risk and favorable lifestyle. Among participants at high genetic risk, the standardized 5-year cancer incidence significantly reduced from 7.23% to 5.51% for men and from 5.77% to 3.69% for women having a favorable lifestyle.

“Individuals at high genetic risk of overall cancer can be identified by CPRS, and risk can be attenuated by adopting a healthy lifestyle,” concluded the study authors.

Clinical Significance

A new indicator of CPRS measures genetic risk for overall cancer, which could help identify individuals with high cancer risk to facilitate decision-making about lifestyle modifications for personalized prevention. In a statement about the study’s findings, Guangfu Jin, PhD, Professor in the Department of Epidemiology at Nanjing Medical University in Nanjing, China, and the corresponding author of the study, said: “Our findings indicate that everyone should have a healthy lifestyle to decrease overall cancer risk. 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.”

Disclosure: Funding for this study was provided by the National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, National Key Research and Development Program of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, CAMS Innovation Fund for Medical Sciences, and the National Science Foundation for Post-Doctoral Scientists of China. For full disclosures of the study authors, visit cancerres.aacrjournals.org.