Mortality and incidence of new primary cancers in men with prostate cancer: A Danish population-based cohort study

Background: Prostate cancer (PC) survivors may have an increased risk of new primary cancers (NPCs) due to shared risk factors or PC-directed treatments. Methods: Using Danish registries, we conducted a cohort study of men with (n = 30,220) and without PC (n = 151,100) (comparators), matched 1:5 on age and PC diagnosis/index date. We computed incidence rates of NPCs per 10,000 person years (PY) and associated 95% confidence intervals (CI), and used Cox proportional hazards regression to compute hazard ratios (HRs) and 95%CI, adjusting for comorbidities. In order to obviate any impact of shorter survival among prostate cancer patients, we censored comparator patients when the matched prostate cancer patient died or was censored. Results: Follow-up spanned 113,487 PY and 462,982 PY in the PC and comparison cohorts, respectively. 65% of the cohorts were aged >70 years at diagnosis. Among PC patients, 51% had distant/unspecified stage, and 63% had surgery as primary treatment. The PC cohort had lower incidence of NPCs than their comparators. The adjusted HR of NPC among men with PC versus the comparators was 0.84 (95%CI = 0.80, 0.88). Lowest HRs were among older men, those with distant stage, and were particularly evident for cancers of the brain, liver, pancreas, respiratory, upper gastrointestinal, and urinary systems. Conclusions: We find no evidence of an increased risk of NPCs among men with PC. The deficit of NPCs among men with PC may be a true effect but is more likely due to lower levels of risk factors (e.g., smoking) in PC patients versus comparators, clinical consideration of cancers at new organs as metastases rather than new primaries, or under-recording/under-reporting of NPCs among PC patients.     

ABO Blood Group and Incidence of Skin Cancer

Background

Previous studies have examined the association between ABO blood group and the risk of some malignancies. However, no prospective cohort study to date has examined the association between ABO blood group and the risk of skin cancer.

Methodology/Principal Findings

Using two large cohorts in the US, we examined ABO blood type and incidence of skin cancer, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). We followed up study participants (70,650 female nurses and 24,820 male health professionals) on their diagnosis of incident skin cancer from cohort baseline (1976 in women and 1986 in men) until 2006. Study participants reported their blood type in 1996 in both cohorts. During the follow-up, 685 participants developed melanoma, 1,533 developed SCC and 19,860 developed BCC. We used Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of each type of skin cancer. We observed that non-O blood group (A, AB, and B combined) was significantly associated with a decreased risk of non-melanoma skin cancer overall. Compared to participants with blood group O, participants with non-O blood group had a 14% decreased risk of developing SCC (multivariable HR: 0.86; 95% CI: 0.78, 0.95) and a 4% decreased risk of developing BCC (multivariable HR: 0.96; 95% CI: 0.93, 0.99). The decreased risk of melanoma for non-O blood group was not statistically significant (multivariable HR: 0.91; 95% CI: 0.78, 1.05).

Conclusion/Significance

In two large independent populations, non-O blood group was associated with a decreased risk of skin cancer. The association was statistically significant for non-melanoma skin cancer. Additional studies are needed to confirm these associations and to define the mechanisms by which ABO blood type or closely linked genetic variants may influence skin cancer risk.     

Smoking and risk of meningioma: A meta-analysis

Objective: The relationship between smoking and the development of meningioma has been investigated in several epidemiological studies. However, the results of these studies are inconsistent. We conducted a meta-analysis in order to identify any potential association. Methods: PubMed, the Cochrane Library, and EMBASE databases were searched to identify relevant articles that investigated the risk of meningioma following cigarette smoking. Two researchers evaluated study eligibility and extracted the data independently, and disagreements were resolved by discussion. The variables used to estimate the pooled risk of smoking in meningioma development were the multivariate-adjusted risk estimates presented in the literature. Results: Seven case–control and two cohort studies were included in this meta-analysis. The pooled estimated risks associated with ever smoking for meningioma were 1.02 (95% confidence interval (CI): 0.85–1.21) in the case–control studies, 0.93 (95% CI: 0.83–1.04) in the cohort studies and 0.95 (95% CI: 0.87–1.05, P = 0.32) in all studies when the cohort and case–control data were combined. Subgroup analyses suggested that the risk estimates were 1.49 (95% CI: 1.06–2.09, P = 0.02), 0.86 (95% CI: 0.65–1.13), 0.79 (95% CI: 0.50–1.25) and 0.84 (95% CI: 0.69–1.03) for men, women, current and past smoking respectively. Sensitivity analyses restricted to studies with different adjustments for confounders yielded similar results. No evidence of publication bias was observed. Conclusion: Our meta-analysis suggests that there is no association between ever smoking and the risk of meningioma. However, a small but significant risk elevation is present among men smokers.     

Laparoscopic Versus Open Radical Nephrectomy for Renal Cell Carcinoma: a Systematic Review and Meta-Analysis

BACKGROUND: The aim of this study is to summarize and quantify the current evidence on the therapeutic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with renal cell carcinoma (RCC) in a meta-analysis. METHODS: Data were collected by searching Pubmed, Embase, Web of Science, and ScienceDirect for reports published up to September 26, 2016. Studies that reported data on comparisons of therapeutic efficacy of LRN and ORN were included. The fixed-effects model was used in this meta-analysis if there was no evidence of heterogeneity; otherwise, the random-effects model was used. RESULTS: Thirty-seven articles were included in the meta-analysis. The meta-analysis showed that the overall mortality was significantly lower in the LRN group than that in the ORN group (odds ratio [OR] =0.77, 95% confidence interval [CI]: 0.62-0.95). However, there was no statistically significant difference in cancer-specific mortality (OR = 0.77, 95% CI: 0.55-1.07), local tumor recurrence (OR = 0.86, 95% CI: 0.65-1.14), and intraoperative complications (OR = 1.27, 95% CI: 0.83-1.94). The risk of postoperative complications was significantly lower in the LRN group (OR = 0.71, 95% CI: 0.65-0.78). In addition, LRN has been shown to offer superior perioperative results to ORN, including shorter hospital stay days, time to start oral intake, and convalescence time, and less estimated blood loss, blood transfusion rate, and anesthetic consumption. CONCLUSION: LRN was associated with better surgical outcomes as assessed by overall mortality and postoperative complications compared with ORN. LRN has also been shown to offer superior perioperative results to ORN.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.     

Body mass index and screening for colorectal cancer: gender and attitudinal factors

Background: Overweight/obese women and men are at increased risk for colorectal cancer (CRC) incidence and mortality. Research examining body mass index (BMI) and CRC screening has had mixed results. A clearer understanding of the extent to which high-BMI subgroups are screened for CRC is needed to inform planning for CRC screening promotions targeting BMI. Methods: Data were obtained from a random, population-based sample of women and men at average-risk for CRC (aged 50–75 years) during 2004 (n = 1098). Multiple logistic regression analyses were conducted to evaluate whether BMI category was significantly associated with the probability of reporting recent CRC screening and with the probability of agreeing with statements denoting attitudes/perceptions about CRC and screening. Attitudes/perceptions about CRC and screening were evaluated as potential mediators and moderators of the association between BMI category and CRC screening. Results: After controlling for characteristics associated with CRC screening, overweight and obese women were each 40% less likely to have CRC screening than women with normal-BMI (OR = 0.6, 95% CI:0.4–0.9 and OR = 0.6, 95% CI:0.3–0.9). BMI category was unrelated to screening among men. Obese women (but not men) were less aware than normal-BMI women that obesity increased risk for CRC (OR = 0.5, 95% CI:0.3–0.9) and less worried about CRC (OR = 0.5, 95% CI:0.3–0.8). However, findings suggest that attitudes/perceptions about CRC and screening did not mediate or moderate the association between BMI category and CRC screening. Conclusion: Overweight/obese women are at increased risk for CRC because of their greater BMI and their propensity not to screen for CRC. Study findings suggest that potentially modifiable perceptions, e.g., lack of awareness of risk for CRC and less worry about CRC, in this subgroup may not explain the relationship between BMI category and reduced screening.     

Acute myeloid leukemia incidence following radiation therapy for localized or locally advanced prostate adenocarcinoma

Introduction: The effect of radiation therapy on acute myeloid leukemia incidence among prostate cancer patients has not been sufficiently elucidated despite evidence that acute myeloid leukemia is a consequence of therapeutic radiation in other primary malignancies. Therefore, we investigated the effect of definitive therapy with radiation therapy (external beam radiation therapy [EBRT] or brachytherapy) on acute myeloid leukemia incidence in a population-based cohort of patients with localized or locally advanced prostate cancer. Methods: We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men (n = 168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy (i.e. no EBRT, brachytherapy, or surgery). Results: The cohort yielded 184 acute myeloid leukemia cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative risk of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR = 2.05, 95% CI 1.29, 3.26; brachytherapy: HR = 1.22, 95% CI 0.46, 3.22; surgery: HR = 1.24, 95% CI 0.77, 1.98). Conclusions: Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma.     

Sedentary work and the risks of colon and rectal cancer by anatomical sub-site in the Canadian census health and environment cohort (CanCHEC)

BackgroundSedentary behaviour is a potential risk factor for colorectal cancer. We examined the association between sedentary work, based on body position, and colorectal cancer risk in Canadians.MethodsA working body position category (a. sitting; b. standing and walking; c. sitting, standing, and walking; d. other) was assigned to occupations reported by 1991 Canadian Census respondents based on national occupational counselling guidelines. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for cancers of the colon (overall, proximal, and distal) and rectum in men and women newly diagnosed from 1992 to 2010.ResultsCompared to “sitting” jobs, men in occupations with “other” (non-sitting, −standing, or −walking) body positions had a weakly significant reduced colon cancer risk (HR = 0.93, 95% CI: 0.89, 0.98) primarily attributed to protection at the distal site (HR = 0.90, 95% CI: 0.84, 0.97). Men in “standing and walking” and “sitting, standing, and walking” jobs did not have significantly reduced colon cancer risks. No effects were observed for rectal cancer in men or colon and rectal cancer in women.ConclusionThe two significant findings of this analysis should be followed-up in further investigations with additional information on potential confounders. Null findings for rectal cancer were consistent with other studies.     

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis

BackgroundThe aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association.MethodsA cohort of 8391 patients with newly diagnosed Dukes’ A-C CRC (2009–2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality.ResultsIn the Scottish cohort, statin use before diagnosis (HR = 0.84, 95% CI 0.75–0.94), but not after (HR = 0.90, 95% CI 0.77–1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I² = 0%,heterogeneity P = 0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n = 86,622, pooled HR = 0.82, 95% CI 0.79–0.86) but this association was less apparent and more heterogeneous (I² = 67%,heterogeneity P = 0.03) with statin use after diagnosis in 4 studies (n = 19,152, pooled HR = 0.84, 95% CI 0.68–1.04).ConclusionIn a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies.     

Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk)

Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) were investigated. Data were available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034 mg/d (range: 0–8531 mg/d) for men and 970 mg/d (0–6695 mg/d) for women, median intake of flavan-3-ol monomers was 233 mg/d (0–3248 mg/d) for men and 217 (0–2712 mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow-up, there were 8463 cardiovascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk.     

Diabetes,physical activity and breast cancer among Hispanic women

Purpose: We assessed the association between diabetes and breast cancer and whether physical activity modified the effect of diabetes on breast cancer in Hispanic women. Methods: We used data from a case-control study of breast cancer among Hispanic women aged 30–79 conducted between 2003 and 2008 on the Texas–Mexico border. In-person interviews were completed with 190 incident breast cancer cases ascertained through surgeons and oncologists, and 979 controls who were designated as both high-risk (n = 511) and low-risk (N = 468) for breast cancer (with respective response rates of 97%, 83% and 74%). Results: After adjustment for menopausal status and mammography screening, there was no effect of diabetes on breast cancer risk (high-risk control group odds ratio [OR] 1.02, 95% confidence interval [CI] 0.71–1.48; low-risk control group OR 0.87, 0.58–1.30). Women who had a diabetes history and did not exercise were at no risk of breast cancer (OR 0.96, 95% CI 0.63–1.48) or a slightly reduced breast cancer risk (low-risk control group OR 0.72, 95% CI 0.46–1.15) depending on the control group used, while women with diabetes who did exercise had significantly reduced breast cancer risk (OR 0.41, 95% CI 0.21–0.83) regardless of the control group used (high-risk control group p-value for interaction = 0.013, low-risk control group p-value for interaction 0.183). Conclusions: Should other studies confirm our results, physical activity should be explored as a means of reducing breast cancer risk in diabetic women.     

Multiple myeloma and occupation: A pooled analysis by the International Multiple Myeloma Consortium

Objective: We investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case–control studies. Methods: We calculated the odds ratio and its 95% confidence interval for selected occupations with unconditional regression analysis in 1959 MM cases and 6192 controls, by pooling study-specific risks using random-effects meta-analysis. Exposure to organic solvents was assessed with a job-exposure matrix (JEM). Results: Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR = 1.50, 95% CI 0.9–2.3), while other farming jobs did not. Metal processors (OR = 1.55, 95% CI 0.9–2.3), female cleaners (OR = 1.32, 95% CI 1.0–1.8), and high level exposure to organic solvents (OR = 1.38, 95% CI 0.96–1.8) also showed moderately increased risks. Conclusions: Additional case–control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

The association between serum selenium and gestational diabetes mellitus: A systematic review and meta-analysis

BackgroundResults of the studies about association between serum selenium concentration and gestational hyperglycemia are inconsistent. Some studies have demonstrated that women with gestational diabetes mellitus (GDM) have lower Se concentrations while contrary results are reported in other studies.AimThe aim of this study is to compare the serum Se concentration in women with GDM and normoglycemic pregnant women via a systematic review and meta-analysis.MethodsA computerized literature search on four databases (PubMed, Cochrane register of control trials, Scopus and Google scholar) was performed from inception through August 2013. Necessary data were extracted and random effects model was used to conduct the meta-analysis.ResultsSix observational studies (containing 147 women with GDM and 360 normoglycemic pregnant women) were found, which had compared serum Se concentration in women suffering from GDM with normal pregnant ones. Our meta-analysis revealed that serum Se concentration was lower in women with GDM compared to normoglycemic pregnant women (Hedges = −1.34; 95% CI: −2.33 to −0.36; P < 0.01). Stratified meta-analysis demonstrated that concentration of Se in the sera of women with GDM was lower than normal pregnant women both in second and third trimesters, but the result was not significant in second trimester (second trimester: Hedges = −0.68; 95% CI: −1.60−0.25; P = 0.15, third trimester: Hedges = −2.81; 95% CI: −5.21 to −0.42; P < 0.05). It was also demonstrated that serum Se status was lower in pregnant women with impaired glucose tolerance (IGT) compared to normoglycemic pregnant women (Hedges = −0.85; 95% CI: −1.18 to −0.52).ConclusionThe available evidences suggest that serum Se concentration is significantly lower in pregnant women with gestational hyperglycemia compared to normal pregnant women.     

Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor I in adult men

ObjectiveLower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men.Methods and resultsFrom two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n = 330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06–1.78), p = 0.02] and two hormones [HR 2.88 (95% CI 1.32–6.29), p < 0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3–0.7%, p = 0.03).ConclusionsOur results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality.     

The impact of chemokine receptor CXCR4 on breast cancer prognosis: A meta-analysis

Background: C-X-C chemokine receptor type 4 (CXCR4) has been implicated in the invasiveness and metastasis of diverse cancers. However, the published data remain controversial on the correlation between CXCR4 expression level, as well as its subcellular distribution in tumor cells, and the clinical outcome of patients with breast cancer. Methods: To identify the precise role of CXCR4 in the clinical outcome of breast cancer, we performed a meta-analysis including 15 published studies. Original data included the hazard ratios (HRs) of overall survival (OS) and disease-free survival (DFS) in breast cancer with high CXCR4 expression versus low expression. We pooled hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the hazard. Results: A total of 15 published studies (including 3104 patients) were eligible. Overall survival (OS) and disease-free survival (DFS) of breast cancer were found to be significantly related to CXCR4 expression level, with the HR being 1.65 (95%CI: 1.34–2.03; P < 0.00001) and 1.94 (95%CI: 1.42–2.65; P < 0.00001) respectively. Stratified analysis according to subcellular distribution of CXCR4 showed that high expression in whole cells, cytoplasm and nucleus could predict unfavorable OS, with the HR of 2.02 (95%CI: 1.43–2.85; P < 0.0001), 1.57 (95%CI: 1.13–2.18; P = 0.007), and 1.47 (95%CI: 1.19–1.81; P = 0.0004) respectively. As for DFS, elevated expression level of CXCR4 both in whole cells and cytoplasm predicted a poor outcome, with the HR being 2.23 (95%CI: 1.48–3.37; P = 0.0001) and 1.76 (95%CI: 1.11–2.80; P = 0.02), while high expression in the nucleus had no statistical significance, with HR 1.15 (95%CI: 0.52–2.55; P = 0.73). Conclusions: Increased CXCR4 expression, especially in whole cells and cytoplasm, may serve as a poor prognostic indicator in patients with breast cancer. Future studies are warranted to investigate the relationship between CXCR4 expression and survival of patients with breast carcinoma, which could help predict the clinical outcome and guide clinical decision-making for therapy.     

Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

ObjectivesZinc may play a role in the development of type 2 diabetes (T2D), because it is involved in antioxidant and anti-inflammatory activities. However, the role of zinc in the etiology of T2D has been poorly investigated. This study was conducted to study the association of serum zinc on T2D risk in middle-aged and older Finnish men.MethodsThis was a 20-year prospective follow-up study on 2220 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) who were 42 to 60 years old at baseline in 1984–1989. The main outcome was incident T2D. Serum zinc, body mass index (BMI), fasting blood glucose (FBG), serum insulin, C-reactive protein (CRP) and, in a subset of 751 participants, insulin-like growth factor-binding protein-1 (IGFBP-1), were measured. Also, the homeostatic model assessment (HOMA) was used to quantify insulin resistance (HOMA-IR), beta-cell function (HOMA-β) and insulin sensitivity (HOMA-IS).ResultsAt baseline, serum zinc was associated with higher BMI, serum insulin, HOMA-IR, HOMA-β and IGFBP-1 and lower HOMA-IS. During the average follow-up of 19.3 years, 416 men developed T2D. Men in the highest quartile of serum zinc had 60% higher risk (95% CI 20–113%; P-trend < 0.001) for incident T2D compared with the men in the lowest quartile, after multivariate adjustments. This association was attenuated after adjustment for BMI (HR = 1.39, 95% CI 1.04–1.85; P-trend = 0.013) or HOMA-IS (HR = 1.38, 95% CI 1.04–1.83; P-trend = 0.015), whereas adjustment for the other factors had only modest impact on the association.ConclusionHigher serum zinc was associated with higher risk of T2D; effects of zinc on BMI and insulin sensitivity may partly explain the association. Further prospective studies are warranted to confirm our results and explore potential mechanisms.     

Hypomethylation of repetitive elements in blood leukocyte DNA and risk of gastric lesions in a Chinese population

BackgroundTo explore the association between hypomethylation of repetitive elements (LINE-1, Sat2, and ALU) in blood leukocyte DNA and risks of gastric lesions, and development of gastric cancer (GC), a population-based study was conducted in a high-risk area of GC in China.MaterialsMethylation levels were determined by MethyLight in 902 subjects with various gastric lesions from two cohort studies at baseline and 276 subjects with long-term follow-up data.ResultsThe frequency of LINE-1 or Sat2 hypomethylation was significantly increased in subjects with dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. The odds ratios (ORs) were 2.22 [95% confidence interval (CI): 1.45–3.40] for LINE-1 and 1.58 (95% CI: 1.14–2.21) for Sat2. A dose–response pattern was found for the risk of DYS and LINE-1 hypomethylation (P-trend < 0.001). Further stratified analysis indicated that the frequency of LINE-1 or Sat2 hypomethylation was higher in subjects with Helicobacter pylori infection. The ORs were 1.83 (95% CI: 1.12–2.99) for LINE-1 and 1.44 (95% CI: 1.01–2.05) for Sat2. The follow-up data indicated that the risk of progression to GC was increased in intestinal metaplasia (IM) subjects with LINE-1 hypomethylation (OR = 2.82; 95% CI: 1.17–6.77) or Sat2 hypomethylation (OR = 2.78; 95% CI: 1.15–6.74). The risk of progression to GC was also increased in DYS subjects with Sat2 hypomethylation (OR = 5.24; 95% CI: 2.00–13.74).ConclusionsThese findings suggest that hypomethylation of repetitive elements in blood leukocytes is associated with the risks of advanced gastric lesions and development of GC.     

Cancer incidence in the AGRICAN cohort study (2005–2011)

BackgroundNumerous studies have been conducted among farmers, but very few of them have involved large prospective cohorts, and few have included a significant proportion of women and farm workers. Our aim was to compare cancer incidence in the cohort (overall, by sex, and by work on farm, occupational status and pesticide use) within the general population.MethodsMore than 180,000 participants in the AGRICAN cohort were matched to cancer registries to identify cancer cases diagnosed from enrolment (2005–2007) to 31st December 2011. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs).ResultsOver the period, 11,067 incident cancer cases were identified (7304 men and 3763 women). Overall cancer incidence did not differ between the cohort and the general population. Moreover, SIRs were significantly higher for prostate cancer (SIR = 1.07, 95%CI 1.03–1.11) and non-Hodgkin lymphoma (SIR = 1.09, 95%CI 1.01–1.18) among men, skin melanoma among women (SIR = 1.23, 95%CI 1.05–1.43) and multiple myeloma (men: SIR = 1.38, 95%CI 1.18–1.62; women: SIR = 1.26, 95%CI 1.02–1.54). In contrast, SIRs were lower for upper aerodigestive tract and respiratory cancers. Increase in risk was greater in male farm workers for prostate and lip cancer, in female farm workers for skin melanoma, and in male farm owners for multiple myeloma. Moreover, incidence of multiple myeloma and skin melanoma was higher among male and female pesticide users respectively.ConclusionWe found a decreased incidence for tobacco-related cancers and an increased incidence of prostate cancers, skin melanoma and multiple myeloma. Specific subgroups had a higher cancer incidence related to occupational status and pesticide use.     

Validez predictiva del cuestionario VIDA considerando pérdida funcional,institucionalización o muerte en pacientes pluripatológicos

IntroductionThe VIDA Spanish questionnaire assesses instrumental activities of daily living (IADL) in elderly people, and has shown to have adequate content, construct validity, and reliability.The objective was to analyse its predictive validity in patients with multiple morbidities aged ≥ 65 years without severe/total dependence in basic activities (BADL, Barthel index ≥ 60 points), by measuring any changes in this severe/total level of dependence, institutionalisation, or death at 8 and 18 months of follow-up.MethodsA prospective study of a diagnostic test was conducted on 197 patients (8 months) and 185 (18 months) included in the multiple morbidities program according to stratification by Adjusted Clinical Groups (ACG) or by fulfilling the Ollero criteria. Patients that were institutionalised, at the end of life, or on dialysis, or with a baseline Barthel index ≥ 60 points were excluded. The VIDA questionnaire was applied at baseline. The other baseline variables included age, gender, Charlson index, number of drugs, and Lawton-Brody index.The outcome event was changing the Barthel index to < 60, or institutionalisation, or death, in each follow-up period.ResultsThe median age was 81 years (IQR 74.5-85), and 45.2% were women.At 8 months, the best cut-off point for VIDA was ≤ 31 points (Sensitivity [S] 81.5%, [95% CI; 61.2-93.0]; Specificity (Sp) 58.2% [95% CI; 50.4-65.7], PPV 23.7%; NPV 95.2%), ≤ 30 in women, ≤ 34 in men. And at 18 months, ≤ 29 points (S 61.4 [95% CI; 47.6-73.7]; Sp 76.6 [95% CI; 68.1-83.4]; PPV 53.9; NPV 81.7).ConclusionsOverall cut-off points are provided as well as those for gender, predicting severe/total BADL decline, or institutionalization or death in patients with multiple morbidities. It seems to detect short-term events better and rules them out in the long term.