A Prospective Study on Metabolic Risk Factors and Gallbladder Cancer in the Metabolic Syndrome and Cancer (Me-Can) Collaborative Study

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Abstract

Objective

To investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC).

Methods

The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements.

Results

During an average follow-up of 12.0 years (SD = 7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73).

Conclusion

This study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer.

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Most cited references 33

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The metabolic syndrome

Robert H. Eckel, Scott M. Grundy, Paul Zimmet (2005)

The metabolic syndrome is a common metabolic disorder that results from the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) will be applicable worldwide. The pathophysiology seems to be largely attributable to insulin resistance with excessive flux of fatty acids implicated. A proinflammatory state probably contributes to the syndrome. The increased risk for type 2 diabetes and cardiovascular disease demands therapeutic attention for those at high risk. The fundamental approach is weight reduction and increased physical activity; however, drug treatment could be appropriate for diabetes and cardiovascular disease risk reduction.

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Fasting serum glucose level and cancer risk in Korean men and women.

Sun Jee, Heechoul Ohrr, Jae Sull … (2005)

Diabetes is a serious and costly disease that is becoming increasingly common in many countries. The role of diabetes as a cancer risk factor remains unclear. To examine the relationship between fasting serum glucose and diabetes and risk of all cancers and specific cancers in men and women in Korea. Ten-year prospective cohort study of 1,298,385 Koreans (829,770 men and 468,615 women) aged 30 to 95 years who received health insurance from the National Health Insurance Corp and had a biennial medical evaluation in 1992-1995 (with follow-up for up to 10 years). Death from cancer and registry-documented incident cancer or hospital admission for cancer. During the 10 years of follow-up, there were 20,566 cancer deaths in men and 5907 cancer deaths in women. Using Cox proportional hazards models and controlling for smoking and alcohol use, the stratum with the highest fasting serum glucose (> or =140 mg/dL [> or =7.8 mmol/L]) had higher death rates from all cancers combined (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.22-1.37 in men and HR, 1.23; 95% CI, 1.09-1.39 in women) compared with the stratum with the lowest level (<90 mg/dL [<5.0 mmol/L]). By cancer site, the association was strongest for pancreatic cancer, comparing the highest and lowest strata in men (HR, 1.91; 95% CI, 1.52-2.41) and in women (HR, 2.05; 95% CI, 1.43-2.93). Significant associations were also found for cancers of the esophagus, liver, and colon/rectum in men and of the liver and cervix in women, and there were significant trends with glucose level for cancers of the esophagus, colon/rectum, liver, pancreas, and bile duct in men and of the liver and pancreas in women. Of the 26,473 total cancer deaths in men and women, 848 were estimated as attributable to having a fasting serum glucose level of less than 90 mg/dL. For cancer incidence, the general patterns reflected those found for mortality. For persons with a diagnosis of diabetes or a fasting serum glucose level greater than 125 mg/dL (6.9 mmol/L), risks for cancer incidence and mortality were generally elevated compared with those without diabetes. In Korea, elevated fasting serum glucose levels and a diagnosis of diabetes are independent risk factors for several major cancers, and the risk tends to increase with an increased level of fasting serum glucose.

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Data quality at the Cancer Registry of Norway: an overview of comparability, completeness, validity and timeliness.

Inger Kristin Larsen, Milada C Småstuen, Tom Borge Johannesen … (2009)

To provide a comprehensive evaluation of the quality of the data collected on both solid and non-solid tumours at the Cancer Registry of Norway (CRN). Established quantitative and semi-quantitative methods were used to assess comparability, completeness, accuracy and timeliness of data for the period 1953-2005, with special attention to the registration period 2001-2005. The CRN coding and classification system by and large follows international standards, with some further subdivisions of morphology groupings performed in-house. The overall completeness was estimated at 98.8% for the registration period 2001-2005. There remains a variable degree of under-reporting particularly for haematological malignancies (C90-95) and tumours of the central nervous system (C70-72). For the same period, 93.8% of the cases were morphologically verified (site-specific range: 60.0-99.8%). The under-reporting in 2005 due to timely publication is estimated at 2.2% overall, based on the number of cases received at the registry during the following year. This review suggests the routines in place at the CRN yields comparable data that can be considered reasonably accurate, close-to-complete and timely, thereby justifying our policy of the reporting of annual incidence one year after the year of diagnosis.

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Author and article information

Contributors

Konradin Metze: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 21 February 2014

Volume: 9

Issue: 2

Electronic Location Identifier: e89368

Affiliations

[1 ]Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria

[2 ]Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway

[3 ]Norwegian Institute of Public Health, Oslo/Bergen, Norway

[4 ]Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden

[5 ]Department of Internal Medicine, Division of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden

[6 ]Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany

[7 ]Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark

[8 ]Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden

[9 ]Cancer Registry of Norway, Institute of Population-based Cancer Research, Montebello, Oslo, Norway

[10 ]Agency for Preventive and Social Medicine, Bregenz, Austria

[11 ]Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden

[12 ]Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

University of Campinas, Brazil

Author notes

* E-mail: Hanno.Ulmer@ 123456i-med.ac.at

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: WB ME TB CH BL GN AE TS SS JM RS ST HC GH HJ PS HU. Analyzed the data: WB ME SS TS CH HJ HU. Contributed reagents/materials/analysis tools: TB JM HC GH. Wrote the paper: WB ME TB CH BL GN AE TS SS JM RS ST HC GH HJ PS HU.

Article

Publisher ID: PONE-D-13-49247

DOI: 10.1371/journal.pone.0089368

PMC ID: 3931760

PubMed ID: 24586723

SO-VID: 06b3b7c4-2556-4f40-8b05-946ef0b1405d

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 22 November 2013

Date accepted : 19 January 2014

Page count

Pages: 7

Funding

World Cancer Research Fond International 2007/09 and 2010/14 to Pär Stattin and Medical University of Innsbruck (MUI START). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

A Prospective Study on Metabolic Risk Factors and Gallbladder Cancer in the Metabolic Syndrome and Cancer (Me-Can) Collaborative Study

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Abstract

Objective

Methods

Results

Conclusion

Related collections

PLOS Climate

Most cited references 33

The metabolic syndrome

Fasting serum glucose level and cancer risk in Korean men and women.

Data quality at the Cancer Registry of Norway: an overview of comparability, completeness, validity and timeliness.

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