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Sex Disparities and Female Reproductive and Hormonal Factors Associated with Risk of Pancreatic Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Katzke, Verena A. ; Dutta, Srimanti ; Rasokat, Anna ; Archibugi, Livia ; Capurso, Gabriele ; Peduzzi, Giulia ; Gentiluomo, Manuel ; Canzian, Federico ; Eriksen, Anne Kirstine and Tjønneland, Anne , et al. (2025) In Cancers 17(14).
Abstract

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15–1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC... (More)

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15–1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC among women with greater attained body height, meat consumption and cigarettes smoked (1.12 (1.05–1.19) per 5 cm, 1.18 (1.02–1.36) per 100 g/d, 1.42 (1.27–1.59) per 10/d; respectively). Among child-bearing women, long cumulative duration of breastfeeding was inversely associated with risk of PC (HR 0.74, 95% CI 0.61–0.89) for >5.7 months of breastfeeding (median) relative to ≤5.7 months and among HRT users, cumulative duration of HRT use was inversely associated with PC risk (HR 0.71, 95% CI 0.53–0.95, >2.4 versus ≤2.4 years). Further reproductive and hormonal factors, such as age at menarche, number of full-term pregnancies, age at menopause, or use of oral contraceptives, were not significantly associated with PC risk. Conclusions: Pooled analyses of large cohort studies are needed to confirm these results, and detailed data on the type and intensity of HRT are required to better evaluate its effect.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
EPIC study, hormonal factors, pancreatic cancer, reproductive factors, sex differences, women
in
Cancers
volume
17
issue
14
article number
2275
publisher
MDPI AG
external identifiers
  • pmid:40723159
  • scopus:105011690019
ISSN
2072-6694
DOI
10.3390/cancers17142275
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 by the authors.
id
2c99a91e-2c4d-4f76-bce9-caa4fe3c6154
date added to LUP
2025-12-15 15:56:38
date last changed
2025-12-16 09:38:51
@article{2c99a91e-2c4d-4f76-bce9-caa4fe3c6154,
  abstract     = {{<p>Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15–1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC among women with greater attained body height, meat consumption and cigarettes smoked (1.12 (1.05–1.19) per 5 cm, 1.18 (1.02–1.36) per 100 g/d, 1.42 (1.27–1.59) per 10/d; respectively). Among child-bearing women, long cumulative duration of breastfeeding was inversely associated with risk of PC (HR 0.74, 95% CI 0.61–0.89) for &gt;5.7 months of breastfeeding (median) relative to ≤5.7 months and among HRT users, cumulative duration of HRT use was inversely associated with PC risk (HR 0.71, 95% CI 0.53–0.95, &gt;2.4 versus ≤2.4 years). Further reproductive and hormonal factors, such as age at menarche, number of full-term pregnancies, age at menopause, or use of oral contraceptives, were not significantly associated with PC risk. Conclusions: Pooled analyses of large cohort studies are needed to confirm these results, and detailed data on the type and intensity of HRT are required to better evaluate its effect.</p>}},
  author       = {{Katzke, Verena A. and Dutta, Srimanti and Rasokat, Anna and Archibugi, Livia and Capurso, Gabriele and Peduzzi, Giulia and Gentiluomo, Manuel and Canzian, Federico and Eriksen, Anne Kirstine and Tjønneland, Anne and Dahm, Christina C. and Truong, Therese and Canonico, Marianne and Laouali, Nasser and Schulze, Matthias B. and Tumino, Rosario and Masala, Giovanna and Agnoli, Claudia and Dansero, Lucia and Panico, Salvatore and Crous-Bou, Marta and Molina-Montes, Esther and Dorronsoro, Ane and Chirlaque, María Dolores and Guevara, Marcela and Butt, Salma Tunå and Sund, Malin and Christakoudi, Sofia and Aglago, Elom K. and Weiderpass, Elisabete and Gunter, Marc and Campa, Daniele and Kaaks, Rudolf}},
  issn         = {{2072-6694}},
  keywords     = {{EPIC study; hormonal factors; pancreatic cancer; reproductive factors; sex differences; women}},
  language     = {{eng}},
  number       = {{14}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Sex Disparities and Female Reproductive and Hormonal Factors Associated with Risk of Pancreatic Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort}},
  url          = {{http://dx.doi.org/10.3390/cancers17142275}},
  doi          = {{10.3390/cancers17142275}},
  volume       = {{17}},
  year         = {{2025}},
}