How Genes and Habits Together Shape Cancer Risk

Researchers looked at data from the UK Biobank, focusing on people of European background. They included 159,744 men and 175,037 women. From these participants they inferred 50 common HLA variants across 11 classic HLA genes. A lifestyle score was built from diet, smoking, alcohol, exercise and body weight, placing each person into a good, medium or poor category. The participants were followed for a median of 13 years, during which 35,132 new cancer cases were recorded.

The team then examined how each factor alone related to cancer. Using statistical models they found that an unhealthy lifestyle raised the overall chance of cancer by about 38% in men and 44% in women. Certain HLA variants were linked to higher risk of lung, prostate and non‑Hodgkin lymphoma in men, and to kidney and endometrial cancer in women. When they looked at men and women separately, the same trends held, showing that sex matters for these genetic effects.

When they looked at combined effects, they saw that a poor lifestyle together with a specific set of HLA alleles (B08:01, DQA105:01, DQB102:01, DRB103:01) greatly increased lung cancer risk in men, with an interaction measure (RERI) between 2.6 and 3.2. For women, the combination of an unhealthy lifestyle and HLA‑A*24:02 raised kidney cancer risk, giving an RERI of 3.2 with a confidence interval from 1.2 to 5.3. The scientists say these results need to be checked again, especially in groups that are not of European descent and in studies where HLA types are measured directly.

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