The analysis of genetic and lifestyle factors with cancer incidence in a general-population cohort suggested that genetic cancer risk may be reduced by adopting a healthy lifestyle. An incidence-weighted overall cancer polygenic risk score (CPRS) was constructed based on 20 cancer site-specific polygenic risk scores. Lifestyle was determined according to smoking, alcohol consumption, physical activity, body mass index, and diet. In 202,842 men and 239,659 women from the UK Biobank, 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 (HRs) of 1.27 or 1.91 for overall cancer, respectively, for men, and 1.21 or 1.62, respectively, for women. A joint effect of genetic and lifestyle factors on overall cancer risk was observed, with HRs reaching 2.99 for men and 2.38 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 was significantly reduced from 7.23% to 5.51% for men and from 5.77% to 3.69% for women having a favorable lifestyle. Similar trends were observed in all genetic risk categories. Almost everyone is susceptible to at least one type of cancer. The findings indicate that everyone should have a healthy lifestyle to decrease cancer risk. Source: https://cancerres.aacrjournals.org/
