Obesity has become a public health problem worldwide. There are many different opinions about the correlation between obesity and cancer risk. Is obesity the main culprit of cancer? Are all indicators of obesity associated with the risk of developing cancer? The results of a pooled analysis showed that obesity (BMI,
waist-hip ratio and weight gain) is significantly associated with the risk of incidence and death of esophageal adenocarcinoma, multiple myeloma, pancreatic cancer, colon cancer, rectal cancer, biliary system, pancreatic cancer, breast cancer, endometrial cancer, ovarian cancer and kidney cancer, with sufficient evidence level. 1. Background Cancer is a lethal disease, with 12.7 million new cases and 7.6 million deaths per year. Overweight is associated with morbidity and mortality from many diseases, including cancer, type 2 diabetes, and cardiovascular disease. In the past 40 years, obesity has increased by a factor of 1 in women and a factor of 3 in men. Many Meta-analyses have explored the relationship between obesity and cancer, but the results have been inconsistent. Meta-analyses may exaggerate the relationship between obesity and cancer due to confounding bias and selective bias in the included studies themselves. The results of a recent pooled analysis found a significant association between type 2 diabetes and the development of some cancers, but only 14% of the 27 included studies were free from any potential bias. To further clarify the available evidence and its quality, systematic reviews and Meta-analyses were pooled to explore the relationship between obesity indicators and the risk of cancer incidence and death. 2.Methods A search of PubMed,Embase and Cochrane Data-base of Systematic
Reviews before May 2015 was accepted all studies of systematic evaluation or meta-analysis of the relationship between obesity indicators and cancer risk and death. Obesity indicators included body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio, body weight, weight gain values, and weight loss values after slimming surgery. 3. results Forty-nine papers including 204 meta-analyses were included in the analysis. These meta-analyses included 507 single-arm cohort or case-control studies, 371 (73.2%) of the cohort studies, 134 (26.4%) of the control studies, and 2 (0.4%) of the cross-selection studies. There were 5645 patients in the cancer group and 1766389 in the control group. 177 studies had >1000 cases in the cancer group. With a threshold of P<0.05, 80% (76/95) were statistically significant using the fixed-effect model and 76% (72/95) were statistically significant using the random utility model. Using P<0.001 as the threshold, 69% (66/95) and 62% (59/95) of the studies using both models were statistically significant. With a P<
10-6 as the threshold, the proportions were 57% (54/95) and 37% (35/95). Of the 35 most statistically rigorous meta-analyses, 31 showed that obesity increased the risk of 11 cancers, including adenocarcinoma of the esophagus, multiple myeloma, colorectal cancer, liver cancer, tumors of the biliary system (gallbladder, extrahepatic bile duct, and pot belly) pancreatic cancer, postmenopausal breast cancer, endometrial cancer, and kidney cancer. 4 showed a negative association between esophageal squamous cancer and lung cancer and obesity. The weight range was 0.57-1.90, and 61% ranged from 0.80-1.20. Eight cancers did not differ between men and women, including esophageal adenocarcinoma, esophageal squamous carcinoma, multiple myeloma, leukemia, gastric cancer, lung cancer, kidney cancer, and thyroid cancer. However, for every 5 kg/m2 increase in BMI in men
kg/m2 increased the risk of colon cancer by 30% (RR 1.03 95% CI 1.25-1.35) and rectal cancer by 9% (RR 1.09 95% CI
1.06-1.13). Women had a 12% increased risk of colon cancer (RR 1.12 95% CI 1.06-1.17) and a 2% increased risk of rectal cancer (RR 1.02
95% CI 0.99-1.05). The risk of melanoma increased by 17% per 5 kg/m2 increase in BMI in men (RR 1.17 95%CI 1.05-1.30), while there was no association in women (RR
0.96 95%CI 0.93-1.00). Forty-four percent (42/95) of the meta-analyses had P≤0.10 by Q-test. 21% (20/95) of the meta-analyses regarding esophageal, colon, liver, lung, endometrial, prostate and thyroid cancer, melanoma, leukemia) had relative heterogeneity (I2=50-75%) and 16% (15/95) had greater heterogeneity (I2
>75%). Thirteen percent (12/95) showed a correlation between obesity and cancer incidence and mortality, with a correlation level of “strong”. Obesity was measured by BMI (n=10), waist-to-hip ratio (n=1), and weight gain (n=1), and increased BMI significantly increased the risk of esophageal adenocarcinoma, colorectal cancer in men, biliary system and pancreatic cancer, premenopausal endometrial cancer, kidney cancer, and multiple myeloma. An increase in weight and waist-to-hip ratio significantly increases the risk of postmenopausal breast and endometrial cancers in women without hormone replacement therapy (HRT). For every 5 increase in BMI in men
kg/m2 increased the risk of colorectal cancer by 9% (RR 1.09 95% CI 1.06-1.13) and biliary system cancer by 56% (RR 1.56 95% CI
1.34-1.81). For every 5 kg increase in body weight, the risk of breast cancer in postmenopausal women without HRT increased by 11% (RR 1.11 95% CI
1.09-1.13). The risk of endometrial cancer increased by 21% (RR 1.21 95% CI 1.13-1.29) for every 0.1 increase in waist-to-hip ratio. The correlation level of 18% (17/95) was “highly suggestive”. Positive associations with risk included colon cancer (BMI and waist circumference), liver cancer (BMI), postmenopausal breast cancer (BMI, waist circumference, weight, weight gain), postmenopausal endometrial cancer types I and II (BMI), and kidney cancer (BMI). The negative correlation with BMI included esophageal squamous cancer and lung cancer. 25% (24/95) correlation level was “suggestive” and 20% (19/95) was “weak”. 4. Conclusion Obesity is significantly associated with 11 primary cancers (esophageal adenocarcinoma, multiple myeloma, pancreatic cancer, colon cancer, rectal cancer, biliary system, pancreatic cancer, breast cancer, endometrial cancer, ovarian cancer and kidney cancer), and the level of evidence is sufficient. Further large prospective international studies are needed to validate this result. Obesity has become a worldwide public health problem, and clarifying the relationship between obesity and cancer is beneficial for screening high-risk groups and is an important strategy for primary and secondary prevention. Comment: Obesity is an important health problem and is closely related to cardiovascular disease and diabetes. There are countless studies on the relationship between obesity and cancer. It is generally accepted that obesity is associated with the risk of cancer development and death. However, in these studies, the obesity indicators used, the primary tumor sites of interest, and the target populations vary. The results of some of these studies have made people fearful of “fat”. In this paper, the correlation between obesity and primary cancers was clarified through a pooled analysis and the extent of the correlation was further analyzed. The results show that obesity is more closely associated with digestive system tumors and female hormone-related tumors. The results of the study provide a more objective analysis of the relationship between obesity and cancer. Of course, this is a pooled analysis based on published meta-analysis, with data from before 2015, without incorporating the latest research data, and is a retrospective analysis. Prospective study results are needed for further validation.