The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes ...tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.
In 2011, the U.S. National Lung Cancer Screening Trial (NLST) reported a 20% reduction of lung cancer mortality after regular screening by low‐dose computed tomography (LDCT), as compared to X‐ray ...screening. The introduction of lung cancer screening programs in Europe awaits confirmation of these first findings from European trials that started in parallel with the NLST. The German Lung cancer Screening Intervention (LUSI) is a randomized trial among 4,052 long‐term smokers, 50–69 years of age, recruited from the general population, comparing five annual rounds of LDCT screening (screening arm; n = 2,029 participants) with a control arm (n = 2,023) followed by annual postal questionnaire inquiries. Data on lung cancer incidence and mortality and vital status were collected from hospitals or office‐based physicians, cancer registries, population registers and health offices. Over an average observation time of 8.8 years after randomization, the hazard ratio for lung cancer mortality was 0.74 (95% CI: 0.46–1.19; p = 0.21) among men and women combined. Modeling by sex, however showed a statistically significant reduction in lung cancer mortality among women (HR = 0.31 95% CI: 0.10–0.96, p = 0.04), but not among men (HR = 0.94 95% CI: 0.54–1.61, p = 0.81) screened by LDCT (pheterogeneity = 0.09). Findings from LUSI are in line with those from other trials, including NLST, that suggest a stronger reduction of lung cancer mortality after LDCT screening among women as compared to men. This heterogeneity could be the result of different relative counts of lung tumor subtypes occurring in men and women.
What's new?
Low‐dose computed tomography (LDCT) is an emerging tool for early lung cancer detection. Here, as part of the German Lung Cancer Screening Intervention trial, the benefits of annual LDCT screening were examined in long‐term smokers ages 50 to 69. In men and women combined, no statistically significant reduction in lung cancer mortality was observed after five annual rounds of LDCT screening compared to controls. Separate analyses by sex, however, revealed significant reductions in lung cancer mortality among the women who underwent LDCT. The findings support the systematic use of LDCT in lung cancer screening, though critical optimization strategies await investigation.
Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices ...to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m
) or obese (BMI ≥ 30 kg/m
) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
The effect of major epidemiologic risk factors for ovarian cancer has been reviewed in the light of several hormonal hypotheses, including the gonadotropin, androgens, progesterone, estrogens, ...insulin-like growth factor-I, and insulin hypotheses. The role of inclusion cyst formation and Mullerian epithelium differentiation in the pathology of the disease are also briefly outlined. Although based on limited data, the observed tendency in current evidence suggests possible etiologic roles for elevated androgens and estrogens and decreased progesterone in the pathogenesis of ovarian cancer. A direct effect of gonadotropins cannot be entirely ruled out, but it is plausible that their effect on ovarian cancer risk is mediated by stimulation of ovarian steroidogenesis. Insulin-like growth factor-I also emerges as a hormone that may be directly involved in the pathogenesis of the disease, but thus far only one prospective study has examined this association. Hyperinsulinemia is an unlikely risk factor for ovarian cancer. The observed tendency for an increased risk with androgens from ovarian origin (in premenopausal women), the lack of association with adrenal androgens, and the relatively weak associations observed with obesity, hormonal replacement therapy use, and endogenous hormones after menopause suggest that ovarian synthesis of sex steroids rather than their circulating levels may be etiologically important. More data from prospective studies will be crucial to improve our understanding of the etiologic role of endogenous hormones in the pathogenesis of ovarian cancer. Such data will ultimately provide opportunities for research targeted; at early detection and preventive interventions.
Circulating concentrations of lipid biomarkers are associated with risk of cardiovascular diseases (CVD). The evidence for a relationship with cancer risk, however, is not entirely consistent. This ...study aims to assess the relationships of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein (a) (apo(a)), apoB-100, and lipoprotein(a) (Lp(a)) with risk of common cancer forms and total cancer mortality in comparison to incidence and mortality of CVD.
We selected a case-cohort sample out of the prospective EPIC-Heidelberg study, including a random subcohort (n = 2739), and cases of cancer (n = 1632), cancer mortality (n = 761), CVD (n = 1070), and CVD mortality (n = 381). Concentrations of lipid biomarkers were measured in pre-diagnostic blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Prentice-weighted Cox regression models.
High levels of circulating apoB-100 and TG were inversely associated and high HDL-C levels were positively associated with breast cancer risk (highest vs. lowest quartile (Q4 vs. Q1), HR
0.71, 95% CI 0.52-0.98; HR
0.65, 0.46-0.92; and HR
1.39, 1.01-1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HR
1.43, 1.02-2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HR
0.52, 0.30-0.91). High TC, HDL-C, apo(a), and Lp(a) levels were associated with a reduction in total cancer mortality (Q4 vs. Q1, HR
0.71, 0.54-0.94; HR
0.67, 0.50-0.91; HR
0.71, 0.54-0.93; and HR
0.74, 0.57-0.98). All lipid biomarkers were associated with risk of myocardial infarction, whereby TC, apoB-100, TG, and Lp(a) were positively and HLD-C and apo(a) inversely associated with risk. Only high levels of TG were associated with an increased risk of stroke. None of the lipids were associated with risk of colorectal cancer and with risk of CVD mortality after multivariable adjustments.
This prospective study demonstrates inverse associations of lipid biomarkers with cancer incidence and mortality, with the exception of positive associations of HDL-C and Lp(a) with breast and prostate cancer risk, respectively. Thus, the observed cancer risk pattern clearly differs from the CVD risk pattern.
Objective To examine the prevalence of lower urinary tract symptoms (LUTS) in males of the general population. Materials and Methods In our analysis, we included 8627 men, 48-79 years of age, who ...participated in the fourth follow-up (FUP) of EPIC-Heidelberg (2007-2009) and replied to questions on LUTS. According to the International Prostate Symptom Score questionnaire, men were categorized as having mild (0-7 points), moderate (8-19 points), or severe LUTS (20-35 points). In addition, we examined progression of LUTS among 7821 men, who also participated in FUP 5 (2010-2012). Results There were 75.3% of men who reported mild, 22.0% who reported moderate, and 2.7% who reported severe LUTS. The prevalence increased with age. At FUP 4, 5.8% (mild symptoms) to 39.7% (severe LUTS) of participants reported use of any type of benign prostatic hyperplasia or LUTS medication. Nocturia, that is, getting up at night at least twice, was the most common symptom, followed by incomplete emptying of the bladder and urgency. There were 54.8% of men who reported worse LUTS in FUP 5, but 27.1% reported an improvement in symptoms. Conclusion About a quarter of middle-aged and elderly men reported clinically relevant LUTS. Whereas symptoms in some men actually improve, more than half of men experience worsening of symptoms over a 3-year period in time.
It has long been proposed that albumin, bilirubin and uric acid may inhibit cancer development due to their anti-oxidative properties. However, there is a lack of population-based studies on blood ...levels of these molecules and cancer risk.
Associations between pre-diagnostic serum albumin, bilirubin and uric acid and the risks of common cancers as well as cancer death in the EPIC-Heidelberg cohort were evaluated by multivariable Cox regression analyses. A case-cohort sample including a random subcohort (n=2739) and all incident cases of breast (n=627), prostate (n=554), colorectal (n=256), and lung cancer (n=195) as well as cancer death (n=761) that occurred between baseline (1994-1998) and 2009 was used.
Albumin levels were inversely associated with breast cancer risk (hazard ratio
(95% CI): 0.71 (0.51, 0.99), P
=0.004) and overall cancer mortality (HR
(95% CI): 0.64 (0.48, 0.86), P
<0.001) after multivariable adjustment. Uric acid levels were also inversely associated with breast cancer risk (HR
(95% CI): 0.72 (0.53, 0.99), P
=0.043) and cancer mortality (HR
(95% CI): 0.75 (0.58, 0.98), P
=0.09). There were no significant associations between albumin or uric acid and prostate, lung and colorectal cancer. Serum bilirubin was not associated with any cancer end point.
The present findings indicate that higher levels of albumin and uric acid are related to lower risks of breast cancer and cancer mortality. Further studies are needed to assess whether the observed associations are causal.
CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 ...can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer.
In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer.
Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9-18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone.
Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0-9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.
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