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. 2024 Jul 26;24(1):903.
doi: 10.1186/s12885-024-12641-8.

Non-genetic factors and breast cancer: an umbrella review of meta-analyses

Anneza Yiallourou  1 , Katerina Pantavou  1 , Georgios Markozannes  2   3 , Antonis Pilavas  1 , Andrea Georgiou  1 , Andria Hadjikou  1 , Mary Economou  1 , Neophytos Christodoulou  4 , Konstantinos Letsos  1 , Elina Khattab  1 , Chrystalleni Kossyva  1 , Maria Constantinou  1 , Melanie Theodoridou  1 , Daniele Piovani  5   6 , Konstantinos Κ Tsilidis  2   3 , Stefanos Bonovas  5   6 , Georgios K Nikolopoulos  7
Affiliations

Non-genetic factors and breast cancer: an umbrella review of meta-analyses

Anneza Yiallourou et al. BMC Cancer. .

Abstract

Background: Previous research has found associations between various non-genetic factors and breast cancer (BrCa) risk. This study summarises and appraises the credibility of the available evidence on the association between non-genetic factors and BrCa risk.

Methods: We conducted an umbrella review of meta-analyses. Medline, Scopus, and the Cochrane databases were systematically searched for meta-analyses examining non-genetic factors and BrCa incidence or mortality. The strength of the evidence was graded in four categories (i.e., weak, suggestive, highly suggestive, convincing).

Results: A total of 781 meta-analyses from 280 publications were evaluated and graded. We included exposures related to anthropometric measurements, biomarkers, breast characteristics and diseases, diet and supplements, environment, exogenous hormones, lifestyle and social factors, medical history, medication, reproductive history, and pregnancy. The largest number of examined associations was found for the category of diet and supplements and for exposures such as aspirin use and active smoking. The statistically significant (P-value < 0.05) meta-analyses were 382 (49%), of which 204 (53.4%) reported factors associated with increased BrCa risk. Most of the statistically significant evidence (n = 224, 58.6%) was graded as weak. Convincing harmful associations with heightened BrCa risk were found for increased body mass index (BMI), BMI and weight gain in postmenopausal women, oral contraceptive use in premenopausal women, increased androstenedione, estradiol, estrone, and testosterone concentrations, high Breast Imaging Reporting and Data System (BIRADS) classification, and increased breast density. Convincing protective factors associated with lower BrCa risk included high fiber intake and high sex hormone binding globulin (SHBG) levels while highly suggestive protective factors included high 25 hydroxy vitamin D [25(OH)D] levels, adherence to healthy lifestyle, and moderate-vigorous physical activity.

Conclusions: Our findings suggest some highly modifiable factors that protect from BrCa. Interestingly, while diet was the most studied exposure category, the related associations failed to reach higher levels of evidence, indicating the methodological limitations in the field. To improve the validity of these associations, future research should utilise more robust study designs and better exposure assessment techniques. Overall, our study provides knowledge that supports the development of evidence-based BrCa prevention recommendations and guidance, both at an individual level and for public health initiatives.

Trial registration: PROSPERO CRD42022370675.

Keywords: Breast cancer; Meta-analysis; Non-genetic factors; Overview of reviews; Systematic review; Umbrella review.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the literature search and study selection process in the umbrella review of meta-analyses on non-genetic risk factors and breast cancer
Fig. 2
Fig. 2
Summary of the classification of non-genetic factors examined in the 781 meta-analyses and the distribution of the grading for their association with breast cancer risk
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. 10.3322/caac.21660 - DOI - PubMed
    1. Joko-Fru WY, Jedy-Agba E, Korir A, Ogunbiyi O, Dzamalala CP, Chokunonga E, et al. The evolving epidemic of breast cancer in sub-Saharan Africa: results from the African cancer registry network. Int J Cancer. 2020;147:2131–41. 10.1002/ijc.33014 - DOI - PubMed
    1. Arpino G, Pensabene M, Condello C, Ruocco R, Cerillo I, Lauria R, et al. Tumor characteristics and prognosis in familial breast cancer. BMC Cancer. 2016;16:924. 10.1186/s12885-016-2962-1 - DOI - PMC - PubMed
    1. Heer E, Harper A, Escandor N, Sung H, McCormack V, Fidler-Benaoudia MM. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. Lancet Glob Heal. 2020;8:e1027–37.10.1016/S2214-109X(20)30215-1 - DOI - PubMed
    1. Parise CA, Bauer KR, Brown MM, Caggiano V. Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999–2004. Breast J. 2009;15:593–602. 10.1111/j.1524-4741.2009.00822.x - DOI - PubMed

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