Linear age‐course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk: An internal replication study of 800, 000 individuals. Issue 1 (18th March 2019)

• Record Type: Journal Article
• Authors: Häggström, Christel; Jonsson, Håkan; Bjørge, Tone; Nagel, Gabriele; Manjer, Jonas; Ulmer, Hanno; Drake, Isabel; Ghaderi, Sara; Lang, Alois; Engeland, Anders; Stattin, Pär; Stocks, Tanja
• Is Part Of: International journal of cancer. Volume 146:Issue 1(2020)
• Page Start: 58
• Page End: 67
• Publication Date: 2019-03-18
• Subjects: survival analysis -- cohort study -- metabolic factors -- cancer risk -- age interaction; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32240
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age‐course. We created two random 50–50% cohorts from six European cohorts comprising 813, 927 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 findings were 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. This 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). These findings are unlikely to be due to chance owing to the replication. The linear age‐interactions in breast cancer may suggest an influence by other age‐related factors than menopause; however, further investigation of age‐related effect modifiers in both breast and liver cancer is needed. Abstract : What's new? While obesity is associated with increased cancer risk, whether associations with underlying metabolic factors, such as body mass index (BMI) and cholesterol, vary with age is uncertain. This investigation of interactions between age and metabolic factors shows that specifically for breast cancer in women and liver cancer in men, elevated BMI and triglyceride levels are associated with decreased risk at younger ages and increased risk at older ages. These association patterns changed linearly with age. For breast cancer, this suggests that aging‐associated factors other than menopause may modify relationships between metabolic factors and risk.