Metabolic syndrome and endometrial cancer risk

BackgroundVarious studies reported direct associations between endometrial cancer risk and individual components of the metabolic syndrome (MetS), i.e. obesity, diabetes, hypertension, and dyslipidemia, but only a few epidemiological studies considered the association with MetS overall.MethodsWe analyzed data from a case–control study including 454 women with incident endometrial cancer and 798 controls admitted to the same hospitals as cases for acute conditions. Different definitions of MetS were considered, including a combination of self-reported history of diabetes, drug-treated hypertension, drug-treated hyperlipidemia, and various measures of (central) obesity. Odds ratios (ORs) were computed from unconditional logistic regression models, adjusted for major confounding factors.ResultsThe multivariate ORs of endometrial cancer were 2.18 for type 2 diabetes, 1.77 for hypertension, 1.20 for hyperlipidemia, between 1.62 and 2.23 for various definitions of central obesity, and 3.83 for women with a body mass index (BMI) >30 kg/m². The risk of endometrial cancer was significantly increased for subjects with MetS, the ORs ranging between 1.67 and 2.77 when waist circumference was included in MetS definition, and 8.40 when BMI was considered instead.ConclusionsThis study indicates a direct association between various MetS components, besides overweight, with the risk of endometrial cancer.     

Metabolic syndrome and risk of cancer mortality in men

BackgroundMetabolic syndrome (MetS) has been linked with an increased risk of developing cancer; however, the association between MetS and cancer mortality remains less clear. Little research has focused on pre-cancer risk factors that may affect the outcome of treatment. The purpose of this study was to examine the association between MetS and all-cancer mortality in men.MethodsThe participants included 33,230 men aged 20–88 years who were enrolled in the Aerobics Centre Longitudinal Study and who were free of known cancer at the baseline.ResultsAt baseline 28% of all the participants had MetS. During an average of 14 years follow-up, there were a total of 685 deaths due to cancer. MetS at baseline was associated with a 56% greater age-adjusted risk in cancer mortality.ConclusionThese data show that MetS is associated with an increased risk of all-cause cancer mortality in men. Based on these findings, it is evident that successful interventions should be identified to attenuate the negative effects of MetS.     

Metabolic syndrome and the risk of breast cancer in postmenopausal women

BackgroundOnly a few small studies investigated the association between postmenopausal breast cancer and metabolic syndrome (MetS) as a single entity.Materials and methodsWe analyzed the data of two Italian and Swiss case–control studies conducted between 1983 and 2007, including 3869 postmenopausal women with incident breast cancer and 4082 postmenopausal controls admitted to the same hospitals as cases for acute conditions. MetS was defined as the presence of at least three components among diabetes, drug-treated hypertension, drug-treated hyperlipidemia, and obesity.ResultsThe odds ratios (ORs) of postmenopausal breast cancer were 1.33 [95% confidence interval (CI) 1.09–1.62] for diabetes, 1.19 (95% CI 1.07–1.33) for hypertension, 1.08 (95% CI 0.95–1.22) for hyperlipidemia, 1.26 (95% CI 1.11–1.44) for body mass index ≥30 kg/m², and 1.22 (95% CI 1.09–1.36) for waist circumference ≥88 cm. The risk of postmenopausal breast cancer was significantly increased for women with MetS (OR = 1.75, 95% CI 1.37–2.22, for three or more MetS components, P for trend for increasing number of components < 0.0001) and the risk was higher at older age (OR = 3.04, 95% CI 1.75–5.29, at age ≥70 years for three or more MetS components).ConclusionsThis study supports a direct association between MetS and postmenopausal breast cancer risk.     

Metabolic syndrome and hepatocellular carcinoma risk

Background:

Hepatocellular carcinoma (HCC) has been associated to diabetes and obesity, but a possible association with the metabolic syndrome (MetS) and its potential interaction with hepatitis is open to discussion.

Methods:

We analysed data from an Italian case–control study, including 185 HCC cases and 404 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models.

Results:

Among the MetS components, diabetes and obesity (i.e, body mass index (BMI)⩾30 kg m⁻²) were positively associated to HCC risk, with ORs of 4.33 (95% CI, 1.89–9.86) and 1.97 (95% CI, 1.03–3.79), respectively. The ORs for the MetS were 4.06 (95% CI, 1.33–12.38) defining obesity as BMI⩾25, and 1.92 (95% CI, 0.38–9.76) defining it as BMI⩾30. The risk increased with the number of MetS components, up to an almost four-fold excess risk among subjects with ⩾2 MetS factors. Among subjects without chronic infection with hepatitis B and/or C, the OR for those with ⩾2 MetS components was over six-fold elevated. There was no consistent association in subjects with serological evidence of hepatitis B and/or C infection.

Conclusion:

This study found that the risk of HCC increases with the number of MetS components in subjects not chronically infected with hepatitis viruses.     

Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can)

Objective

To investigate metabolic factors and their possible impact on risk of thyroid cancer.

Methods

A prospective cohort study was conducted based on seven population-based cohorts in Norway, Austria, and Sweden, in the Metabolic syndrome and Cancer project (Me-Can). Altogether 578,700 men and women with a mean age of 44.0 years at baseline were followed for on average 12.0 years. Relative risk of incident thyroid cancer was assessed by levels of BMI, blood pressure, and blood levels of glucose, cholesterol, triglycerides, and by a combined metabolic syndrome (MetS) score. Risk estimates were investigated for quintiles, and a z score distribution of exposures was analyzed using Cox proportional hazards regression.

Results

During follow-up, 255 women and 133 men were diagnosed with thyroid cancer. In women, there was an inverse association between glucose and thyroid cancer risk, with adjusted RR: 95% CI was 0.61 (0.41?C0.90), p trend = 0.02 in the fifth versus the first quintile, and a positive association between BMI and thyroid cancer risk with a significant trend over quintiles. There was no association between the other metabolic factors, single or combined (Met-S), and thyroid cancer.

Conclusion

In women, BMI was positively, while blood glucose levels were inversely, associated with thyroid cancer.     

Metabolic syndrome and breast cancer prognosis

Metabolic syndrome (MS), conventionally defined by the presence of at least three out of five dysmetabolic traits (abdominal obesity, hypertension, low plasma HDL-cholesterol, high plasma glucose and high triglycerides), has been associated with an increased risk of several age-related chronic diseases, including breast cancer (BC). This may have prognostic implications for BC survivors. 2,092 early stage BC survivors aged 35–70, recruited in eleven Italian centres 0–5 years after surgical treatment (1.74 years on average), were followed-up over 2.8 years on average for additional BC-related events, including BC-specific mortality, distant metastasis, local recurrences and contralateral BC. At recruitment, 20 % of the patients had MS. Logistic regression models were carried out to generate OR and 95 % confidence intervals (CI) for new BC events associated with MS, adjusting for baseline pathological prognostic factors. New BC events occurred in 164 patients, including 89 distant metastases. The adjusted ORs for women with MS versus women without any MS traits were 2.17 (CI 1.31–3.60) overall, and 2.45 (CI 1.24–4.82) for distant metastasis. The OR of new BC events for women with only one or two MS traits was 1.40 (CI 0.91–2.16). All MS traits were positively associated with new BC events, and significantly so for low HDL and high triglycerides. MS is an important prognostic factor in BC. As MS is reversible through lifestyle changes, interventions to decrease MS traits in BC patients should be implemented in BC clinics.     

Metabolic syndrome contributes to an increased recurrence risk of non-metastatic colorectal cancer

Objectives

Epidemiological data suggests a close link between metabolic syndrome (MetS) and non-metastatic colorectal cancer (NMCRC). However, the relationship between MetS and the outcome of NMCRC is less well understood. We aim to evaluate the impact of MetS on the prognosis in NMCRC patients.

Methods

We performed a large cohort study of 1069 NMCRC patients. The Kaplan-Meier method was used to calculate the cumulative survival rate. Cox proportional hazard regression models were used to analyze the prognosis associated with MetS adjusting for clinicopathologic variables.

Results

MetS was identified in 20.7% of NMCRC patients. Patients with MetS were more likely to be older, higher levels of blood glucose, triglycerides, high density lipoprotein, and uric acid than patients without MS (P < 0.05 for all). During a mean period of 59.6 months follow-up, patients with MetS had a statistically significantly lower rate of disease-free survival (DFS) than the patients without MetS (P = 0.014), especially local recurrence (P = 0.040). However, there was no difference in overall survival (P = 0.116). Multivariate analysis showed that the presence of MetS was an independent risk factor for DFS (HR = 0.733, 95%CI 0.545–0.987, P = 0.041), but not for OS (P = 0.118).

Conclusions

MetS is associated with an increased recurrence risk of NMCRC.     

Metabolic syndrome and outcomes following early-stage breast cancer

The prevalence of risk factors contributing to metabolic syndrome (MetS) is increasing, and numerous components of MetS are associated with increased primary breast cancer (BC) risk. However, less is known about the relationship of MetS to BC outcomes. The aim of this study was to evaluate whether MetS, characterized by increased weight, hypertension, low HDL-cholesterol, high triglycerides, and diabetes or impaired glucose tolerance, is associated with risk of second breast cancer events (SBCE) and BC-specific mortality. Retrospective cohort study of women diagnosed with incident early-stage (I-II) BC between 1990 and 2008, enrolled in an integrated health plan. Outcomes of interest were SBCE, defined as recurrence or second primary BC, and BC-specific mortality. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for time-varying exposure to MetS components while accounting for potential confounders and competing risks. Among 4,216 women in the cohort, 26 % had ≥3 MetS components and 13 % developed SBCE during median follow-up of 6.3 years. Compared to women with no MetS components, presence of MetS (≥3 components) was associated with increased risk of SBCE (HR = 1.50, 95 % CI 1.08–2.07) and BC-specific mortality (HR = 1.65, 95 % CI 1.02–2.69). Of the individual components, only increased weight was associated with increased risk of SBCE (HR = 1.26, 95 % CI 1.06–1.49). MetS is associated with modestly increased risk of SBCE and BC-specific mortality. Given the growing population of BC survivors, further research in larger and more diverse populations is warranted.     

Metabolic syndrome and the risk of prostate cancer in Finnish men: a population-based study.

OBJECTIVE: Individual components of metabolic syndrome have been linked to an increased risk for prostate cancers. We hypothesized that metabolic syndrome itself could confer an increased risk for incident prostate cancer. METHODS: The participants were a population-based sample of 1,880 men from eastern Finland without history of cancer or diabetes mellitus at baseline. RESULTS: The metabolic syndrome (WHO criteria) was present in 357 (19%) of subjects. During an average follow-up of 13 years, a total of 183 cancers occurred, of which 56 were due to prostate cancer. The metabolic syndrome at baseline was related to a 1.9-fold (95% confidence interval, 1.1-3.5) risk of prostate cancer after adjustment for age, alcohol consumption, physical fitness, and energy, fat, fiber, calcium, vitamin E, and alpha-linolenic acid intake. The association between metabolic syndrome and risk of prostate cancer was stronger among overweight and obese men with a body mass index > or = 27 kg/m2 (adjusted relative risk, 3.0; 95% confidence interval, 1.2-7.3) than in lighter men (relative risk, 1.8; 95% confidence interval, 0.7-4.7). CONCLUSIONS: Middle-aged men with the metabolic syndrome were more likely to develop prostate cancer in this prospective population-based study. This finding suggests that efforts to curb the epidemic of overweight and sedentary lifestyle and the accompanying metabolic syndrome may decrease the risk for prostate cancer.     

Metabolic syndrome and risk of bladder cancer: prospective cohort study in the metabolic syndrome and cancer project (Me‐Can)

There are little data on the putative association between factors in the metabolic syndrome (MetS) and risk of bladder cancer. In the Metabolic Syndrome and Cancer project (Me‐Can), measurements of height, weight, blood pressure and circulating levels of glucose, cholesterol, and triglycerides had been collected from 578,700 subjects in cohorts in Norway, Austria, and Sweden. We used Cox proportional hazard models to calculate relative risks (RRs) of bladder cancer by exposures divided into quintiles, in categories according to the World Health Organisation (WHO) and as a continuous standardized variable (z‐score with mean = 0 and standard deviation = 1) for each separate component and its standardized sum, a composite MetS score. RRs were corrected for random error in measurements. During a mean follow‐up of 11.7 years (SD = 7.6), 1,587 men and 327 women were diagnosed with bladder cancer. Significant associations with risk were found among men per one unit increment of z‐score for blood pressure, RR = 1.13 (95% CI 1.03–1.25), and the composite MetS score, RR = 1.10 (95% CI 1.01–1.18). Among women, glucose was nonsignificantly associated with risk, RR = 1.41 (95% CI 0.97–2.06). No statistically significant interactions were found between the components in the MetS in relation to bladder cancer risk. Hypertension and a composite MetS score were significantly but modestly associated with an increased risk of bladder cancer among men and elevated glucose was associated with a nonsignificant increase in risk among women.     

Metabolic factors and breast cancer risk in Korean women

Purpose

Metabolic factors have been suggested to be associated with breast cancer. However, the findings are inconsistent among studies. We conducted a case–control study in Korean women to evaluate the association between metabolic factors and premenopausal and postmenopausal breast cancer.

Methods

Incident breast cancer cases (270 women) and their controls (540 women) matched by age and menopausal status were recruited from the recipients of a health examination at the same institution. Five relevant factors of metabolic syndrome were evaluated. Odds ratios (OR) and 95 % confidence intervals (CI) for the association were estimated by conditional logistic regression analysis.

Results

Proportions of cases and controls with each factors were 25.6 and 20.6 % for obesity (body mass index ≥ 25 kg/m²), 17.4 and 17.4 % for high fasting glucose (≥5.55 mmol/L or use of hypoglycemic medication), 13.0 and 18.9 % for high triglyceride (≥1.69 mmol/L), 26.3 % and 23.9 % for low high-density lipoprotein cholesterol (<1.29 mmol/L), and 29.6 and 30.6 % for high blood pressure (≥130/or 85 mmHg or use of antihypertensive medication), respectively. Although only the obesity was associated with an increased risk of postmenopausal breast cancer (OR = 2.24; 95 % CI 1.22–4.10) among individual metabolic factors, women with aggregation of three or more metabolic factors as defined by international diabetes federation criteria showed greater risk for postmenopausal breast cancer compared with women without any factor (OR = 2.36; 95 % CI 1.10–5.10).

Conclusions

Although obesity was the only metabolic factor associated with postmenopausal breast cancer, the presence of other metabolic factors may further increase the risk of postmenopausal breast cancer when combined with obesity.     

Metabolic syndrome affects breast cancer risk in postmenopausal women: National Cancer Institute of Naples experience

Postmenopausal women show the highest incidence of breast cancer in the female population and are often affected by metabolic syndrome. Metabolic syndrome (MS)--characterized by central adiposity, insulin resistance, low serum high-density lipoprotein cholesterol (HDL-C), high serum triglyceride and high blood pressure--seems to be strictly correlated to breast carcinogenesis. We enrolled 777 healthy women and women with breast cancer in our nested case-control study to evaluate the association between MS and breast cancer, analyzing anthropometric parameters (weight, height, BMI, waist and hip circumference), blood pressure, serum HDL-C, triglyceride, fasting plasma glucose, insulin, testosterone and uric acid levels and administering a questionnaire about physical activity, food intake, tobacco use, alcohol abuse, personal and familial history of disease. We found an higher prevalence of metabolic syndrome (30%) in postmenopausal breast cancer patients compared to healthy women (19%). None of the individual MS features was strong enough to be considered responsible for breast carcinogenesis alone. However, of the 63 postmenopausal breast cancer cases associated to MS, 30% presented three or more MS features, suggesting that the activation of multiple molecular pathways underlying MS might contribute to tumorigenesis. Our data support the hypothesis that MS may be an indicator of breast cancer risk in postmenopausal women. The unsettlement of the hormonal arrangement in postmenopausal, along with an increase in visceral adiposity, probably favour the hormone-dependent cell proliferation, which drives tumorigenesis. Adjustments in lifestyle with physical activity intensification and healthy diet could represent modifiable factors for the primary prevention of sporadic breast cancer.     

Metabolic disorders and breast cancer risk (United States)

Objective: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case–control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). Methods: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65–74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. Results: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0–1.9), that for hirsutism was 1.2 (95% CI 0.81–1.8), and that for polycystic ovaries 1.6 (95% CI 0.8–3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25–1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0–1.4). Conclusions: Androgen-related phenomena are likely to be important in the etiology of breast cancer.