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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

Häggström, Christel ; Jonsson, Håkan ; Bjørge, Tone LU ; Nagel, Gabriele ; Manjer, Jonas LU ; Ulmer, Hanno ; Drake, Isabel LU ; Ghaderi, Sara ; Lang, Alois and Engeland, Anders , et al. (2020) In International Journal of Cancer 146(1). p.58-67
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
age interaction, cancer risk, cohort study, metabolic factors, survival analysis
in
International Journal of Cancer
volume
146
issue
1
pages
10 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:30815851
  • scopus:85074745955
ISSN
0020-7136
DOI
10.1002/ijc.32240
language
English
LU publication?
yes
id
27170e46-ea23-4d7b-8836-ce8427fd95cd
date added to LUP
2019-11-28 11:08:17
date last changed
2024-03-20 00:33:06
@article{27170e46-ea23-4d7b-8836-ce8427fd95cd,
  abstract     = {{<p>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.</p>}},
  author       = {{Häggström, Christel and Jonsson, Håkan and Bjørge, Tone and Nagel, Gabriele and Manjer, Jonas and Ulmer, Hanno and Drake, Isabel and Ghaderi, Sara and Lang, Alois and Engeland, Anders and Stattin, Pär and Stocks, Tanja}},
  issn         = {{0020-7136}},
  keywords     = {{age interaction; cancer risk; cohort study; metabolic factors; survival analysis}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{58--67}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1002/ijc.32240}},
  doi          = {{10.1002/ijc.32240}},
  volume       = {{146}},
  year         = {{2020}},
}