Obesity has been differently associated with breast cancer risk by menopause, which occurs at around 50 years of age in women. Whilst obesity has been associated with a decreased risk of premenopausal breast cancer risk, it has been related to an increased risk of postmenopausal breast cancer. Any potential age-course effects on other obesity-cancer associations are unknown.
In this study, we systematically investigated age-course effects on the associations between obesity and related metabolic factors and risks of a range of cancers. We created two random 50-50% cohorts from six European cohorts comprising more than 800,000 individuals. In the “discovery cohort”, we used Cox regression with attained age as time-scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a P-value below 0.05 were additionally tested in the “replication cohort” where a replicated result was considered evidence of a linear interaction with attained age. These replicated findings were further investigated by flexible parametric survival models for any age-plateaus in their shape of associations with cancer risk across age.
Consistent with other studies, BMI was negatively related to breast cancer risk (n cases=11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. A similar linear and positive age-interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases=444).
We suggest that our findings are unlikely to be due to chance owing to the replication. We speculate that the linear age-interactions in breast cancer may suggest an influence by other age-related factors than by menopause per se. Further investigation of age-related effect modifiers in both breast and liver cancer are needed to clarify the underlying causes to our findings.