Metabolic risk factors and cervical cancer in the metabolic syndrome and cancer project (Me–Can)
Highlights
► Elevated BMI, blood pressure and triglycerides levels are associated with increased cervical cancer risk. ► A combined score of the MetS is associated with increased cervical cancer risk. ► Associations of metabolic factors differ by histological subtype of cervical cancer.
Introduction
Cervical cancer is the third most frequent cancer in women worldwide and the leading cause for cancer mortality predominantly in women from developing countries [1]. The global burden of obesity and its complications is rising [2], which may also have implication for cancer risk. Most cancers (about 80%) of the uterine cervix are squamous cell carcinoma (SCC). Infections with certain human papillomavirus (HPV) strains 16 and 18 are the major risk factor for cervical cancer [[3], [4]]. More than 150 HPV types have been reported, of which about 40 can infect the cervix [5]. Worldwide the contribution of HPV 16 and 18 was estimated at about 63% of all cervical cancers [[6], [7]]. HPV infections are often acquired in younger age and the persistence of HPV infections is virtually observed in all cervical cancer cases [5]. HPV 18 was more common in ADC than SCC cases and was associated with lower age for women with cervical cancer [6]. Other risk factors include long-term use of oral contraceptives, parity, and smoking [8]. The etiology of ADC may differ from that of SCC [[9], [10]] concerning smoking [11], while both entities share risk factors related to reproductive and sexual behavior [[12], [13], [14]]. Thus, differential association with other factors such as the metabolic syndrome (MetS) can be hypothesized.
The MetS is characterized by obesity, hyperglycemia, dyslipidemia and hypertension and has been shown to increase risk of several common cancer types [15]. Results from previous epidemiological studies have shown associations between some metabolic factors and cervical cancer risk [[10], [16], [17], [18]], for example serum triglyceride levels and systolic blood pressure were positively associated with cervical cancer risk [[17], [18], [19]]. Adipose tissue is an endocrine organ producing hormones and proteins e.g. estrogen and adipokines. Immunological alterations are commonly seen in metabolic disease [20]. For estrogen, adipokine and cytokine associations with cervical cancer have been reported [[21], [22]] suggesting that metabolic factors could play a role as co-factors in the cancerogenesis of cervical cancer. However, little is known about the associations between metabolic factors — individually and combined — and the risk of cervical cancer risk.
The aim of this study was to assess the associations between metabolic factors (both individually and combined) and the risk of cervical cancer by subtype in the large prospective metabolic syndrome and cancer project (Me–Can).
Section snippets
Study population
The Me–Can study design, participating cohorts and data collection procedures have been described in detail previously [[23], [24]]. Briefly, for Me–Can studies data from several long-standing cohorts in Austria (the Vorarlberg Health Monitoring and Prevention Program (VHM&PP)), Norway (the Norwegian Counties Study (NCS), the Cohort of Norway (CONOR) and the Age 40 program (40-y)) and Sweden (the Västerbotten Intervention Project (VIP) and the Malmö Preventive Project (MPP)) were pooled. All
Results
In the Me–Can cohort, mean age at measurement was 44.1 (SD 12.3) years and mean follow-up time was 11.3 (SD 6.8) years (Table 1). Among women with at least one year of follow-up, a total of 425 cases of cervical cancer occurred. Information on histology was available for all cases: 337 (79%) cases with SCC, 59 (14%) cases of ADC, and 29 (7%) cases with other histologic types have been registered. Mean age at diagnosis was 50.5 (SD 11.3) years for all cervical cancer cases combined and 50.5
Discussion
The MetS score was associated with increased risk of cervical cancer in this large, prospective study. Several of the individual MetS components including BMI, blood pressure and triglycerides were significantly associated with increased cervical cancer risk. Triglycerides, blood pressure and the MetS score were stronger confined to SCC than to ADC. Among women with attained age 50 years and older metabolic factors were associated with cervical cancer risk.
In our study, BMI by z-score was
Conclusion
The results of this large prospective study provide the first evidence for an association between cervical cancer and both individual and combined metabolic factors including BMI, blood pressure and triglyceride levels. Different risk patterns of metabolic factors by morphology could be related to difference in the pathogenesis.
Conflict of interest
The authors declared no conflicts of interest.
Funding
This work was supported by the World Cancer Research Fund (Grant 2007/09).
Author contribution
Gabriele Nagel, Hanno Ulmer, Tanja Stocks, Tone Bjørge, Annekatrin Lukanova, Jonas Manjer, Håkan Jonsson, and Pär Stattin were involved in the study conception and design. Tanja Stocks and Pär Stattin were involved in financial support. Administrative support was provided by Tanja Stocks, Christel Häggström, Tone Bjørge, Randi Selmer, Hanno Ulmer, Wegene Borena, Andrea Kleiner, Jonas Manjer, Håkan Jonsson, and Pär Stattin. Study material or patients was provided by Hans Concin, Göran Hallmans.
Acknowledgements
We thank, in Norway, the screening team at the former National Health Screening Service of Norway, now the Norwegian Institute of Public Health, the services of CONOR, and the contributing research centers delivering data to CONOR; in the Vorarlberg Heath Monitoring and Prevention Program, Elmar Stimpfl, data base manager, Karin Parschalk at the cancer registry, and Markus Wallner, Christian Bernhard, Andrea Kaufmann, and Gabriela Dür from the Vorarlberg State Government in the Västerbotten
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