Age-course effects on the associations between metabolic factors and cancer risk

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.

Link to the study published in the International Journal of Cancer.

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