Tanja Stocks and colleagues carry out an analysis of six European cohorts and confirm that abnormal glucose metabolism is linked with increased risk of cancer overall and at specific sites.
Prospective studies have indicated that elevated blood glucose levels may be linked with increased cancer risk, but the strength of the association is unclear. We examined the association between blood glucose and cancer risk in a prospective study of six European cohorts.
Methods and Findings
The Metabolic syndrome and Cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden; the current study included 274,126 men and 275,818 women. Mean age at baseline was 44.8 years and mean follow-up time was 10.4 years. Excluding the first year of follow-up, 18,621 men and 11,664 women were diagnosed with cancer, and 6,973 men and 3,088 women died of cancer. We used Cox regression models to calculate relative risk (RR) for glucose levels, and included adjustment for body mass index (BMI) and smoking status in the analyses. RRs were corrected for regression dilution ratio of glucose. RR (95% confidence interval) per 1 mmol/l increment of glucose for overall incident cancer was 1.05 (1.01–1.10) in men and 1.11 (1.05–1.16) in women, and corresponding RRs for fatal cancer were 1.15 (1.07–1.22) and 1.21 (1.11–1.33), respectively. Significant increases in risk among men were found for incident and fatal cancer of the liver, gallbladder, and respiratory tract, for incident thyroid cancer and multiple myeloma, and for fatal rectal cancer. In women, significant associations were found for incident and fatal cancer of the pancreas, for incident urinary bladder cancer, and for fatal cancer of the uterine corpus, cervix uteri, and stomach.
Data from our study indicate that abnormal glucose metabolism, independent of BMI, is associated with an increased risk of cancer overall and at several cancer sites. Our data showed stronger associations among women than among men, and for fatal cancer compared to incident cancer.
Please see later in the article for the Editors' Summary
Large prospective population-based research studies can have the power to discover new associations, and to verify previously proposed associations, between specific risk factors and the subsequent occurrence of disease. One such study, the “Me-Can” (Metabolic syndrome and Cancer project) is investigating associations between cancer incidence and a cluster of metabolic risk factors that make up metabolic syndrome: a large waistline; a high level of fats called triglycerides in the blood; a low level of “good” cholesterol; high blood pressure; and raised blood glucose (hyperglycemia). Here the researchers investigate the associations between one of these risk factors—raised blood glucose—and cancer. It is normal for blood glucose levels to vary before and after meals, but raised levels that persist long-term are known to lead to organ damage and severe complications. It is thought that more than 30% of cancer-related deaths could be prevented by modifying key risk factors, such as tobacco control, modifying diet, staying active, and limiting exposure to environmental risk factors.
Why Was This Study Done?
A previous large research study (including roughly 1.3 million men and women, conducted in Korea) has already evaluated the association between high blood glucose levels and cancer risk, and found that high blood glucose levels were linked with increased risk of cancer—both getting it and dying from it. Studies in European and US populations have also found a link, but they considered relatively small numbers of people and so these could not be used to calculate the risk with respect to specific cancer sites. The researchers carrying out the Me-Can project wanted to verify whether the associations reported in the Korean study also held true for European populations.
What Did the Researchers Do and Find?
The researchers identified 274,126 men and 275,818 women from existing health studies in Norway, Austria, and Sweden for whom data had been recorded on blood glucose level, height, and weight. For each participant a baseline measurement was defined, consisting of data from the first health examination, which had complete data (including a blood glucose measurement and whether the participant smoked). The participants were tracked via national registers for up to around 25 years after the baseline measurement but most commonly for around a decade. Any cancer diagnosis was recorded, whether the participant survived to the end of the study, and causes of death for participants who died during the study. The researchers analyzed the data to assess whether a higher blood glucose level was associated with increased risk of certain cancers, in both men and women. The researchers took weight for height, and smoking into account and adjusted for measurement error from additional blood glucose measurements. The researchers found that, overall, the higher the level of blood glucose, the higher the risk of getting and dying from cancer. Average normal blood glucose levels are about 5 mmol/l, also expressed as 5 mM or 90 mg/dl. For each additional 1 mmol/l increase in blood glucose level, the risk of getting cancer was increased by 5% for men and 11% for women.
What Do These Findings Mean?
The authors concluded that high blood glucose is associated with increased cancer risk. The results largely confirm findings from the Korean study, although there are some differences in the risks of cancers at some specific sites, which may be due to differences in the populations such as genetics, diet, and rates of smoking. Among the strengths of the study are its large sample size and that glucose were measured more than once for many individuals in the study. However, the study is limited in that the researchers did not have data on other possible factors such as genetics, physical activity, or dietary factors, which are linked to cancer incidence and also may be related to blood glucose levels. The researchers propose that controlling blood glucose may lower cancer risk in the population. Although this interpretation is consistent with the data, the study design cannot conclusively demonstrate a causal association between glucose levels and cancer risk.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000201.
The US National Cancer Institute provides online information and statistics on cancer, including risk factors for cancer
The American Heart Association provides information on sugars in the diet, including helpful hints on how to reduce the amount eaten
The UK's National Health Service's Change4Life campaign provides information and ideas for those wishing to make their lifestyle, including diet, more healthy
Cancer Research UK is the world's leading charity dedicated to beating cancer through research. Its websites provide information about cancer and the research it funds