'Strong Evidence': Obesity Tied to 11 Cancers"Strong evidence" supports the association between obesity and 11 cancers, which mostly comprise digestive organ tumors and hormone-related malignancies in women, according to a new analysis published online February 28 in BMJ.
"Other associations could be genuine as well, but there is uncertainty about them," said lead author, Maria Kyrgiou, PhD, MSc, from the Department of Surgery and Cancer, Imperial College London, United Kingdom, in an email to Medscape Medical News.
The new study is known as an "umbrella review" or a "meta-review" because it looks at previous meta-analyses and systematic reviews.
The umbrella review's conclusion — that excess body fat increases most digestive system cancers as well as endometrial and postmenopausal breast cancer — agrees with last year's report from the International Agency for Research on Cancer (IARC), point out a pair of researchers in an accompanying editorial.
However, the IARC has found associations with additional cancers (such as those of the liver, thyroid, and ovary) that the current study did not, write the editorialists, Yikyung Park, ScD, and Graham Colditz, MD, DrPH, from the Division of Public Health Sciences, Washington University School of Medicine, St Louis, Missouri.
Nonetheless, the data are "clear," say the pair. "The unavoidable conclusion from these data is that preventing excess adult weight gain can reduce the risk of cancer."
Excess body fat is potentially the second most important modifiable cancer risk factor after smoking, they say.
"Preventing excess adult weight gain can reduce the risk of cancer. "
Dr Yikyung Park and Dr Graham Colditz
The new umbrella study looked at 95 meta-analyses that reported an association between excess body fat (as measured on a continuous scale) and the risk of developing or dying of cancer. Obesity was defined as a body mass index (BMI) >30 kg/m2.
Dr Kyrgiou explained that a "continuous measure is when the effect of the exposure on the outcome is measured as per unit change, i.e. risk of endometrial cancer per 5 kg/m2 increase in BMI."
There were seven indices of excess body fat/adiposity, including BMI, waist circumference, weight, and waist-to-hip ratio.
The international team of investigators judged that only 13% (12 of 95) of the studies identified in the umbrella review were based on strong statistical evidence (and avoided biases that may have exaggerated the effect of obesity on cancer). In other words, most studies had methodological flaws.
In the end, after analyzing these 12 studies, the team determined that there was an association between body fat and 11 cancer sites: esophageal adenocarcinoma; multiple myeloma; and cancers of the gastric cardia, colon (in men), rectum (in men), biliary tract system, pancreas, breast (postmenopausal), endometrium (premenopausal), ovary, and kidney.
The degree of risk varied. For example, the increase in the risk of developing cancer for every 5-kg/m2increase in BMI ranged from 9% (relative risk, 1.09; 95% confidence interval [CI], 1.06 - 1.13) for rectal cancer among men to 56% (relative risk, 1.56; 95% CI, 1.34 - 1.81) for biliary tract system cancer.
The authors determined that the other 83 studies had highly suggestive (18%), suggestive (25%), and weak (20%) evidence; also, 25% had no evidence of an association.
Prospective studies are needed to draw "firmer conclusions" about which cancers are caused by excess body fat, say the study authors.
Who exactly is at high risk is unknown, they say. If that could be discerned, individuals could be selected for "personalised primary and secondary prevention strategies," the authors write.
BMJ. Published online February 28, 2017.
Adiposity and cancer at major anatomical sites: umbrella review of the literatureBMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j477 (Published 28 February 2017)
Cite this as: BMJ 2017;356:j477
AbstractObjective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer.
Design Umbrella review of systematic reviews and meta-analyses.
Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references.
Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer.
Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings.
Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m2 increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality.
Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.