The global epidemic of obesity is a major public health problem today. Obesity increases the risk of many chronic diseases, such as type 2 diabetes, coronary heart disease, and certain types of ...cancer, and is associated with lower life expectancy. The body mass index (BMI), which is currently used to classify obesity, is only an imperfect measure of abnormal or excessive body fat accumulation. Studies have shown that waist circumference as a measure of fat distribution may improve disease prediction. More elaborate techniques such as magnetic resonance imaging are increasingly available to assess body fat distribution, but these measures are not readily available in routine clinical practice, and health-relevant cut-offs not yet been established. The measurement of biomarkers that reflect the underlying biological mechanisms for the increased disease risk may be an alternative approach to characterize the relevant obesity phenotype. The insulin/insulin-like growth factor (IGF) axis and chronic low-grade inflammation have been identified as major pathways. In addition, specific adipokines such as leptin, adiponectin and resistin have been related to obesity-associated health outcomes. This biomarker research, which is currently further developed with the application of high throughput methods, gives important insights in obesity-related disease etiology and pathophysiological pathways and may be used to better characterize obese persons at high risk of disease development and target disease-causing biomarkers in personalized prevention strategies.
•Obesity is associated with cardiovascular disease, cancer and lower life expectancy.•Obesity is traditionally classified based on the body mass index (BMI).•Taking body fat distribution into account may improve disease prediction.•Insulin/IGF axis and chronic inflammation are major pathophysiological pathways.•A biomarker-guided obesity definition may enable personalized prevention.
The prevalence of obesity has increased substantially in the past in almost all countries of the world, and a further increase is expected for the future. Besides the well-established effects on type ...2 diabetes and cardiovascular disease, there is convincing evidence today that obesity also increases the risk of several types of cancer, including colorectal cancer, postmenopausal breast cancer, endometrial cancer, renal cell carcinoma, esophageal adenocarcinoma, pancreatic cancer, and liver cancer. Obesity probably also increases the risk of ovarian cancer, advanced prostate cancer, gallbladder cancer, and gastric cardia cancer. For some cancer types, there is also some evidence that weight gain during adulthood increases cancer risk, e.g., colorectal cancer, postmenopausal breast cancer, endometrial cancer, and liver cancer. However, for most cancers, it is an open question as to whether vulnerability to weight gain in relation to cancer risk depends on specific life periods. There are a number of plausible mechanisms that may explain the relationship between obesity and cancer risk, including pathways related to insulin resistance, inflammation, and sex hormones. For most cancers, there is only limited evidence that weight loss in adulthood decreases cancer risk, which is primarily due to the limited long-term success of weight loss strategies among obese individuals. There is limited evidence suggesting that obesity may also be associated with poor prognosis among patients with colorectal cancer, breast cancer, endometrial cancer, ovarian cancer, and pancreatic cancer. Taken together, these findings support efforts to prevent weight gain on an individual level as well as on a population level. Whether and to what extent overweight or obese cancer patients benefit from weight loss strategies is unclear and needs to be addressed in future studies.
Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing ...technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (-0.06, 95% CI -0.24, 0.12,
= 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73,
= 81%) and non-significantly lower Bacteroidetes (-4.79, 95% CI -10.77, 1.20,
= 86%). At the genus level, lower relative proportions of
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were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers.
Purpose
Circulating IGF-1 concentrations have been associated with higher cancer risk, particularly prostate, breast and colorectal cancer. There is evidence from observational and intervention ...studies that milk and dairy products intake is associated with higher IGF-1 concentrations, but results were not always consistent. The purpose of this study was to examine the relationship between dairy intake and circulating IGF-1 concentrations in participants of the Second Bavarian Food Consumption Survey, thereby providing data for a German population for the first time.
Methods
In this cross-sectional study of 526 men and women aged 18–80 years, in contrast to most previous investigations, dietary intake was assessed with a more detailed instrument than food frequency questionnaires (FFQs), i.e., by three 24-h dietary recalls conducted on random days close in time to the blood collection. Circulating IGF-1 concentrations were measured in blood samples. Multivariable linear regression models were used to examine the association of dairy intake with IGF-1 concentrations.
Results
Each 400 g increment in daily dairy intake was associated with 16.8 µg/L (95% CI 6.9, 26.7) higher IGF-1 concentrations. Each 200 g increment in milk per day was associated with 10.0 µg/L (95% CI 4.2, 15.8) higher IGF-1. In contrast, we observed no association between cheese or yogurt intake and IGF-1 concentrations.
Conclusions
Our findings are in line with most previous investigations and support the hypothesis that dairy and milk intake are associated with higher IGF-1 concentrations.
The association of vitamin D status with prostate cancer is controversial; no association has been observed for overall incidence, but there is a potential link with lethal disease.
We assessed ...prediagnostic 25-hydroxyvitamin D 25(OH)D levels in plasma, variation in vitamin D-related genes, and risk of lethal prostate cancer using a prospective case-control study nested within the Health Professionals Follow-up Study. We included 1260 men who were diagnosed with prostate cancer after providing a blood sample in 1993-1995 and 1331 control subjects. Men with prostate cancer were followed through March 2011 for lethal outcomes (n = 114). We selected 97 single-nucleotide polymorphisms (SNPs) in genomic regions with high linkage disequilibrium (tagSNPs) to represent common genetic variation among seven vitamin D-related genes (CYP27A1, CYP2R1, CYP27B1, GC, CYP24A1, RXRA, and VDR). We used a logistic kernel machine test to assess whether multimarker SNP sets in seven vitamin D pathway-related genes were collectively associated with prostate cancer. Tests for statistical significance were two-sided.
Higher 25(OH)D levels were associated with a 57% reduction in the risk of lethal prostate cancer (highest vs lowest quartile: odds ratio = 0.43, 95% confidence interval = 0.24 to 0.76). This finding did not vary by time from blood collection to diagnosis. We found no statistically significant association of plasma 25(OH)D levels with overall prostate cancer. Pathway analyses found that the set of SNPs that included all seven genes (P = .008) as well as sets of SNPs that included VDR (P = .01) and CYP27A1 (P = .02) were associated with risk of lethal prostate cancer.
In this prospective study, plasma 25(OH)D levels and common variation among several vitamin D-related genes were associated with lethal prostate cancer risk, suggesting that vitamin D is relevant for lethal prostate cancer.
Insulin‐like growth factor (IGF)−1 is associated with a higher risk of prostate cancer. IGF‐binding protein (IGFBP)−1, a marker for insulin activity, also binds IGF‐1 and inhibits its action. Data on ...IGFBP‐1 and prostate cancer risk are sparse and whether the IGF and insulin axes interact to affect prostate cancer carcinogenesis is unknown. We evaluated the independent and joint influence of prediagnostic plasma levels of IGFBP‐1 (fasting) and IGF‐1 on risk of prostate cancer among 957 cases and 1,021 controls with fasting levels of IGFBP‐1 and 1,709 cases and 1,778 controls with IGF‐1 nested within the Health Professionals Follow‐up Study. Unconditional logistic regression adjusting for matching factors was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Higher prediagnostic fasting IGFBP‐1 levels were associated with lower risk of prostate cancer (highest vs. lowest quartile OR = 0.67, 95% CI 0.52–0.86, ptrend = 0.003), which remained similar after adjusting for IGF‐1. Prediagnostic IGF‐1 was associated with increased risk of prostate cancer (highest vs. lowest quartile OR = 1.28, 95% CI = 1.05–1.56, ptrend = 0.01). The associations with each marker were primarily driven by lower‐grade and non‐advanced prostate cancer. Being low in IGFBP‐1 and high in IGF‐1 did not confer appreciable additional risk (pinteraction = 0.42). In summary, prediagnostic fasting IGFBP‐1 may influence prostate cancer carcinogenesis. Being low in IGFBP‐1 or high in IGF‐1 is sufficient to elevate the risk of prostate cancer.
What's new?
Increased levels of insulin‐like growth factor 1 (IGF‐1) in the circulation are linked to an elevated risk of prostate cancer. The bioavailability of IGF‐1 is limited, however, by IGF binding protein‐1 (IGFBP‐1), though little is known about the relationship between IGFBP‐1 and prostate cancer. In this prospective case‐control study, increased prediagnostic fasting plasma IGFBP‐1 levels were found to be associated with a reduced risk of prostate cancer, and the positive association between circulating IGF‐1 levels and prostate cancer risk was confirmed. The associations were most significant for low‐grade and non‐advanced disease.
The pappalysins pregnancy associated plasma protein-A (PAPP-A) and -A2 (PAPP-A2) act as proteinases of insulin-like growth factor-1 (IGF-1) binding proteins, while stanniocalcin-2 (STC2) was ...identified as a pappalysin inhibitor. While there is some evidence from studies in children and adolescents, it is unclear whether these molecules are related to concentrations of IGF-1 and its binding proteins in adults. We investigated cross-sectionally the association of circulating PAPP-A, PAPP-A2 and STC2 with IGF-1 and its binding proteins (IGFBPs) in 394 adult pretest participants (20-69 years) of the German National Cohort Berlin North study center. Plasma PAPP-A, PAPP-A2, total and free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-5 and STC2 were measured by ELISAs. The associations of PAPP-A, PAPP-A2 and STC2 with IGF-1 or IGFBPs were investigated using multivariable linear regression analyses adjusting for age, sex, body mass index and pretest phase. We observed significant inverse associations of PAPP-A2 (difference in concentrations per 0.5 ng/mL higher PAPP-A2 levels) with total IGF-1 (- 4.3 ng/mL; 95% CI - 7.0; - 1.6), the IGF-1:IGFBP-3 molar ratio (- 0.34%; 95%-CI - 0.59; - 0.09), but not free IGF-1 and a positive association with IGFBP-2 (11.9 ng/mL; 95% CI 5.0; 18.8). PAPP-A was not related to total or free IGF-1, but positively associated with IGFBP-5. STC2 was inversely related to total IGF-1, IGFBP-2 and IGFBP-3 and positively to IGFBP-1. This first investigation of these associations in a general adult population supports the hypothesis that PAPP-A2 as well as STC2 play a role for IGF-1 and its binding proteins, especially for total IGF-1. The role of PAPP-A2 and STC2 for health and disease in adults warrants further investigation.
There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely ...recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers.
Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was ...statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results.
In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer.
Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses' Health Study.
During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk.
Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer.
Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during ...adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor.
In 27,196 females from the Nurses' Health Study 2, aged 25-42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI).
Colorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest ≥4 vs. ≤1.42 servings/day quintile 95% CI 0.94 0.80, 1.11). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 0.42, 0.95), but not proximal (1.01 0.80, 1.28) or distal (0.97 0.76, 1.24) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 0.51, 1.00) but not non-advanced (1.07 0.86, 1.33) adenoma.
In this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.
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