Peripheral Soluble Immune Checkpoint-Related Proteins Were Associated with Survival and Treatment Efficacy of Osteosarcoma Patients, a Cohort Study.

BACKGROUND: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. METHODS: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. RESULTS: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10-2, 1.7 × 10-2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10-4, 9.5 × 10-4, respectively). CONCLUSION: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted.

6-Year trajectory of fasting plasma glucose (FPG) and mortality risk among individuals with normal FPG at baseline: a prospective cohort study.

BACKGROUND: Higher fasting plasma glucose (FPG) levels were associated with an increased risk of all-cause mortality; however, the associations between long-term FPG trajectory groups and mortality were unclear, especially among individuals with a normal FPG level at the beginning. The aims of this study were to examine the associations of FPG trajectories with the risk of mortality and identify modifiable lifestyle factors related to these trajectories. METHODS: We enrolled 50,919 individuals aged ≥ 20 years old, who were free of diabetes at baseline, in the prospective MJ cohort. All participants completed at least four FPG measurements within 6 years after enrollment and were followed until December 2011. FPG trajectories were identified by group-based trajectory modeling. We used Cox proportional hazards models to examine the associations of FPG trajectories with mortality, adjusting for age, sex, marital status, education level, occupation, smoking, drinking, physical activity, body mass index, baseline FPG, hypertension, dyslipidemia, cardiovascular disease or stroke, and cancer. Associations between baseline lifestyle factors and FPG trajectories were evaluated using multinomial logistic regression. RESULTS: We identified three FPG trajectories as stable (n = 32,481), low-increasing (n = 17,164), and high-increasing (n = 1274). Compared to the stable group, both the low-increasing and high-increasing groups had higher risks of all-cause mortality (hazard ratio (HR) = 1.18 (95% CI 0.99-1.40) and 1.52 (95% CI 1.09-2.13), respectively), especially among those with hypertension. Compared to participants with 0 to 1 healthy lifestyle factor, those with 6 healthy lifestyle factors were more likely to be in the stable group (ORlow-increasing = 0.61, 95% CI 0.51-0.73; ORhigh-increasing = 0.20, 95% CI 0.13-0.32). CONCLUSIONS: Individuals with longitudinally increasing FPG had a higher risk of mortality even if they had a normal FPG at baseline. Adopting healthy lifestyles may prevent individuals from transitioning into increasing trajectories.

Prediction of risk and overall survival of pancreatic cancer from blood soluble immune checkpoint-related proteins.

Background: Immune checkpoint inhibition holds promise as a novel treatment for pancreatic ductal adenocarcinoma (PDAC). The clinical significance of soluble immune checkpoint (ICK) related proteins have not yet fully explored in PDAC. Methods: We comprehensively profiled 14 soluble ICK-related proteins in plasma in 70 PDAC patients and 70 matched healthy controls. Epidemiological data of all subjects were obtained through structured interviews, and patients' clinical data were retrieved from electronical health records. We evaluated the associations between the biomarkers with the risk of PDAC using unconditional multivariate logistic regression. Consensus clustering (k-means algorithm) with significant biomarkers was performed to identify immune subtypes in PDAC patients. Prediction models for overall survival (OS) in PDAC patients were developed using multivariate Cox proportional hazards regression. Harrell's concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve and calibration curve were utilized to evaluate performance of prediction models. Gene expressions of the identified ICK-related proteins in tumors from TCGA were analyzed to provide insight into underlying mechanisms. Results: Soluble BTLA, CD28, CD137, GITR and LAG-3 were significantly upregulated in PDAC patients (all q < 0.05), and elevation of each of them was correlated with PDAC increased risk (all p < 0.05). PDAC patients were classified into soluble immune-high and soluble immune-low subtypes, using these 5 biomarkers. Patients in soluble immune-high subtype had significantly poorer OS than those in soluble immune-low subtype (log-rank p = 9.7E-03). The model with clinical variables and soluble immune subtypes had excellent predictive power (C-index = 0.809) for the OS of PDAC patients. Furthermore, the immune subtypes identified with corresponding genes' expression in PDAC tumor samples in TCGA showed an opposite correlation with OS to that of immune subtypes based on blood soluble ICK-related proteins (log-rank p =0.02). The immune-high subtype tumors displayed higher cytolytic activity (CYT) score than immune-low subtype tumors (p < 2E-16). Conclusion: Five soluble ICK-related proteins were identified to be significantly associated with the risk and prognosis of PDAC. Patients who were classified as soluble immune-low subtype based on these biomarkers had better overall survival than those of the soluble immune-high subtype.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Local hepcidin increased intracellular iron overload via the degradation of ferroportin in the kidney.

BACKGROUND: Hepcidin is a key regulator of iron homeostasis. Some studies showed that exogenous hepcidin decreased the expression of divalent metal transporter (DMT1) rather than ferroportin(FPN1) to regulate renal iron metabolism. This study explored the effects of hepcidin synthesized by the kidney and its mechanism of iron regulation. METHODS: In the in vivo experiments, mice were divided into a unilateral ureter obstruction (UUO) model group and a sham operation group, and mice in the UUO model group were sacrificed on days 1, 3, 5 and 7. The expression of renal hepcidin, FPN1, DMT1 and the retention of renal iron were studied. In the in vitro experiments, we overexpressed hepcidin in HK-2 cells. Then we tested the expression of renal hepcidin, FPN1, DMT1 and observed the production of intracellular ferrous ions. RESULTS: Renal hepcidin expression was consistently higher in the UUO group than in the sham group from the first day. The expression of FPN1 gradually decreased, and the expression of DMT1 gradually increased in the UUO model. Intracellular ferrous ions significantly increased on the first day of the UUO model. In hepcidin overexpressed HK-2 cells, the expression of FPN1 was decreased, while the expression of DMT1 has no significant change. In addition, production of intracellular ferrous ions increased. CONCLUSION: local hepcidin can regulate iron metabolism in the kidney by adjusting the expression of FPN1.

A Case-Control Study of Risk Factors for Salivary Gland Cancer in Canada.

Aim. To assess the effect of various lifestyle risk factors on the risk of salivary gland cancer in Canada using data from a population-based case-control study. Methods. Data from a population-based case-control study of 132 incident cases of salivary gland cancer and 3076 population controls were collected through self-administered questionnaire and analysed using unconditional logistic regression. Results. Four or more servings/week of processed meat product was associated with an adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) of 1.62 (1.02-2.58). Nonsignificantly increased ORs were also related to obesity, >7 drinks/week of alcohol consumption, and occupational exposure to radiation. Furthermore, nonsignificantly decreased ORs were found to be associated with high education level (>12 years) (OR = 0.65), high consumption of spinach/squash (OR = 0.62) and all vegetables/vegetable juices (OR = 0.75), and >30 sessions/month of recreational physical activity (OR = 0.78). Conclusions. This study suggests positive associations with consumption of processed meat, smoking, obesity, alcohol drinking, and occupational exposure to radiation as well as negative associations with higher education, consumption of spinach/squash, and physical activity, which suggest a role of lifestyle factors in the etiology of salivary gland cancer. However, these findings were based on small number of cases and were nonsignificant. Further larger studies are warranted to confirm our findings.

Delayed iatrogenic diaphragmatic hernia after thoracoscopic lobectomy.

Postoperative iatrogenic diaphragmatic hernia after thoracoscopic lobectomy is extremely rare. We present a 55-year-old female patient who developed an iatrogenic diaphragmatic hernia with gastric perforation several months after VATS (video-assisted thoracic surgery) left upper lobectomy with systematic lymphadenectomy. During the readmission, urgent laparotomy was performed. Intraoperatively, the choledochoscopy was introduced into left thoracic cavity through the diaphragmatic defect for dissecting the secondary inflammatory adhesions and achieving satisfactory hemostasis. It appears to be an efficient and feasible approach for the patients who have been diagnosed as delayed diaphragmatic hernia concomitant with remarkable intra-abdominal findings and have a history of thoracic surgery. We consider that delayed-onset diaphragmatic hernia should be suspected in patients complaining of nausea or vomiting after VATS procedure, although it is very rare.

Postoperative Regulatory T-Cells and Natural Killer Cells in Stage I Nonsmall Cell Lung Cancer Underwent Video-assisted Thoracoscopic Lobectomy or Thoracotomy.

BACKGROUND: Regulatory T-cells (Treg) play key roles in suppressing cell-mediated immunity in cancer patients. Little is known about perioperative Treg fluctuations in nonsmall cell lung cancer (NSCLC). Video-assisted thoracoscopic (VATS) lobectomy, as a minimal invasive procedure for treating NSCLC, may have relatively less impact on the patient's immune system. This study aimed to observe perioperative dynamics of circulating Treg and natural killer (NK) cell levels in NSCLC patients who underwent major lobectomy by VATS or thoracotomy. METHODS: Totally, 98 consecutive patients with stage I NSCLC were recruited and assigned into VATS or thoracotomy groups. Peripheral blood samples were taken on 1-day prior to operation, postoperative days (PODs) 1, 3, 7, 30, and 90. Circulating Treg and NK cell counts were assayed by flow cytometry, defined as CD4 + CD25 + CD127 low cells in CD4 + lymphocytes and CD56 + 16 + CD3- cells within CD45 + leukocytes respectively. With SPSS software version 21.0 (SPSS Inc., USA), differences between VATS and thoracotomy groups were determined by one-way analysis of variance (ANOVA), and differences between preoperative baseline and PODs in each group were evaluated by one-way ANOVA Dunnett t-test. RESULTS: In both groups, postoperative Treg percentages were lower than preoperative status. No statistical difference was found between VATS and thoracotomy groups on PODs 1, 3, 7, and 30. On POD 90, Treg percentage in VATS group was significantly lower than in thoracotomy group (5.26 ± 2.75 vs. 6.99 ± 3.60, P = 0.012). However, a higher level of NK was found on all PODs except on POD 90 in VATS group, comparing to thoracotomy group. CONCLUSIONS: Lower Treg level on POD 90 and higher NK levels on PODs 1, 3, 7, 30 in VATS group might imply better preserved cell-mediated immune function in NSCLC patients, than those in thoracotomy group.

Chitooligosaccharides suppress the freeze-denaturation of actomyosin in Aristichthys nobilis surimi protein.

Effect of chitooligosaccharides on the denaturation of bighead carp (Aristichthys nobilis) surimi protein during frozen storage at -18 °C was investigated. The addition of 4 g of chitooligosaccharides to 100 g of the bighead carp (A. nobilis) surimi effectively inhibited the inactivation of the Ca(2+)-ATPase during frozen storage at -18 °C for 15 days compared to the control group (p<0.05), while excessive chitooligosaccharides decreased the inhibition effect. The Ca(2+)-ATPase activity of actomyosin for the treatment group decreased gradually during frozen storage at -18 °C, while that of the control dropped drastically and could not be detected after 30 days of storage. On the other hand, the addition of chitooligosaccharides also significantly increased the solubility of actomyosin compared to the control group (p<0.05) during frozen storage at -18 °C up to 120 days.

Breast cancer detection and survival among women with cosmetic breast implants: systematic review and meta-analysis of observational studies.

OBJECTIVES: To evaluate whether the stage distribution among women diagnosed as having breast cancer differs between those who have received breast implants for cosmetic purposes and those with no implants and to evaluate whether cosmetic breast augmentation before the detection of breast cancer is a predictor of post-diagnosis survival. DESIGN: Systematic review of observational studies with two meta-analyses. DATA SOURCES: Systematic search of the literature published before September 2012 conducted in Medline, Embase, Global health, CINAHL, IPAB, and PsycINFO. STUDY SELECTION: Eligible publications were those that included women diagnosed as having breast cancer and who had had augmentation mammaplasty for cosmetic purposes. RESULTS: The overall odds ratio of the first meta-analysis based on 12 studies was 1.26 (95% confidence interval 0.99 to 1.60; P=0.058; I(2)=35.6%) for a non-localized stage of breast cancer at diagnosis comparing women with implants who had breast cancer and women without implants who had breast cancer. The second meta-analysis, based on five studies, evaluated the relation between cosmetic breast implantation and survival. This meta-analysis showed reduced survival after breast cancer among women who had implants compared with those who did not (overall hazard ratio for breast cancer specific mortality 1.38, 95% confidence interval 1.08 to 1.75). CONCLUSIONS: The research published to date suggests that cosmetic breast augmentation adversely affects the survival of women who are subsequently diagnosed as having breast cancer. These findings should be interpreted with caution, as some studies included in the meta-analysis on survival did not adjust for potential confounders. Further investigations are warranted regarding diagnosis and prognosis of breast cancer among women with breast implants.

Use of efficient purse-string stapling technique for esophagogastric anastomosis in minimally invasive Ivor Lewis esophagectomy.

Minimally invasive esophagectomy (MIE) is increasingly accepted in the treatment of locoregional or advanced esophageal cancer. Laparoscopic-thoracoscopic Ivor-Lewis esophagectomy has been proved to be effective in treating middle and distal esophageal cancer, however, intrathoracic esophagogastric anastomosis is technically complex. When using circular stapler for making intrathoracic anastomosis in MIE, both transoral and transthoracic methods are frequently used for delivering the anvil into the esophageal stump. Herein, we report a new method to construct a thoracoscopic esophagogastric anastomosis by using a circular stapler: efficient purse-string stapling technique (EST). This technique is easy to handle and especially good to be used in patients with distal esophageal cancer or expanded esophageal cavity.

Do breast implants adversely affect prognosis among those subsequently diagnosed with breast cancer? Findings from an extended follow-up of a Canadian cohort.

BACKGROUND: Cosmetic breast implants may impair the ability to detect breast cancers. The aims of this study were to examine whether implants and implant characteristics are associated with more advanced breast tumors at diagnosis and poorer survival. METHODS: Study population includes all invasive breast cancer cases diagnosed during follow-up of the large Canadian Breast Implant Cohort. A total of 409 women with cosmetic breast implants and 444 women with other cosmetic surgery were diagnosed with breast cancer. These women were compared for stage at diagnosis using multinomial logistic regression models. Cox proportional hazards regression models were used for breast cancer-specific mortality analyses. Comparisons were also conducted according to implant characteristics. RESULTS: Compared with women with other cosmetic surgery, those with cosmetic breast implants had at later stage breast cancer diagnosis (OR of having stage III/IV vs. stage I at diagnosis: 3.04, 95% confidence interval (CI): 1.81-5.10; P < 0.001). A nonstatistically significant increase in breast cancer-specific mortality rate for women with breast implants relative to surgical controls was observed (HR = 1.32, 95% CI: 0.94-1.83, P = 0.11). No statistically significant differences in stage and breast cancer mortality were observed according to implant characteristics. CONCLUSIONS: At diagnosis, breast cancers tended to be at more advanced stages among women with cosmetic breast implants. Breast cancer-specific survival was lower in these women although the reduction did not reach statistical significance. IMPACT: Further investigations of the effect of breast implants on breast cancer prognosis are warranted.

Canadian breast implant cohort: extended follow-up of cancer incidence.

Cosmetic breast implants are not associated with increased breast cancer incidence, but variations of risk according to implant characteristics are still poorly understood. As well, the assessment of cancer risk for sites other than breast needs to be clarified. The purpose of this study was to fill these research gaps. This study presents an extended analysis of 10 more years of follow-up of a large Canadian cohort of women who received either cosmetic breast implants (n = 24,558) or other cosmetic surgery (15,893). Over 70% of the implant cohort was followed for over 20 years. Cancer incidence among implant women was compared to those of controls using multivariate Poisson models and the general female population using the standardized incidence ratios (SIRs). Women with breast implants had reduced rates of breast and endometrial cancers compared to other surgery women. Subglandular implants were associated to a reduced rate of breast cancer compared to submuscular implants [incidence rate ratio (IRR) = 0.78, 95% confidence interval (CI) = 0.63-0.96] and this reduction persisted over time. We observed a sevenfold increased rate (IRR = 7.36, 95% CI = 1.86-29.12) of breast cancer in the first 5 years after the date of surgery for polyurethane-coated subglandular implant women but this IRR decreased progressively over time (p value for trend = 0.02). We also observed no increased risk of rarer forms of cancer among augmented women. A reduction in breast cancer incidence was observed for women with subglandular implants relative to women with submuscular implants. Possible increase of breast cancer incidence shortly after breast augmentation with polyurethane implants needs to be verified.

Antioxidants and breast cancer risk- a population-based case-control study in Canada.

BACKGROUND: The effect of antioxidants on breast cancer is still controversial. Our objective was to assess the association between antioxidants and breast cancer risk in a large population-based case-control study. METHODS: The study population included 2,362 cases with pathologically confirmed incident breast cancer (866 premenopausal and 1,496 postmenopausal) and 2,462 controls in Canada. Intakes of antioxidants from diet and from supplementation as well as other potential risk factors for breast cancer were collected by a self-reported questionnaire. RESULTS: Compared with subjects with no supplementation, 10 years or longer supplementation of zinc had multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of 0.46 (0.25-0.85) for premenopausal women, while supplementation of 10 years or longer of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc had multivariable-adjusted ORs (95% CIs) of 0.74 (0.59, 0.92), 0.58 (0.36, 0.95), 0.79 (0.63-0.99), 0.75 (0.58, 0.97), and 0.47 (0.28-0.78), respectively, for postmenopausal women. No significant effect of antioxidants from dietary sources (including beta-carotene, alpha-carotene, lycopene, lutein and zeaxanthin, vitamin C, vitamin E, selenium and zinc) or from supplementation less than 10 years was observed. CONCLUSIONS: This study suggests that supplementation of zinc in premenopausal women, and supplementation of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc in postmenopausal women for 10 or more years may protect women from developing breast cancer. However, we were unable to determine the overall effect of total dose or intake from both diet and supplement.

[Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the treatment of HER2-positive advanced gastric cancer].

OBJECTIVE: To evaluate the safety and efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen (irinotecan plus 5-FU/LV) in the treatment of HER2-positive advanced gastric cancer. METHODS: T Thirty-four patients with pathologically confirmed advanced gastric cancer, all positive for the human epidermal growth factor receptor 2 (HER2) as identified by immunohistochemistry and fluorescence in situ hybridization, were randomized into the test group and control group to for treatment with the combined regimen and the FOLFIRI regimen alone, respectively. FOLFIRI regimen was administered every 2 weeks for 2 to 4 cycles. Trsatuzumab was given intravenously on a weekly basis with an initial dose of 4 mg/kg and a subsequent dose of 2 mg/kg. All the patients were assessed for efficacy and toxicity of the treatments. RESULTS: The overall response rate was 58.8% in the test group and 35.3% in the control group, with disease control rates of 88.2% and 64.7%, respectively, showing significant differences between the two groups (P<0.05). The most frequent grade I/II treatment-related adverse events included diarrhea, nausea/vomiting and neutropenia. CONCLUSION: Trsatuzumab combined with FOLFIRI regimen is effective, safe and well tolerated for treatment of HER2-positive advanced gastric cancer.

Epidemiology of cancer of the small intestine.

Cancer of the small intestine is very uncommon. There are 4 main histological subtypes: adenocarcinomas, carcinoid tumors, lymphoma and sarcoma. The incidence of small intestine cancer has increased over the past several decades with a four-fold increase for carcinoid tumors, less dramatic rises for adenocarcinoma and lymphoma and stable sarcoma rates. Very little is known about its etiology. An increased risk has been noted for individuals with Crohn's disease, celiac disease, adenoma, familial adenomatous polyposis and Peutz-Jeghers syndrome. Several behavioral risk factors including consumption of red or smoked meat, saturated fat, obesity and smoking have been suggested. The prognosis for carcinomas of the small intestine cancer is poor (5 years relative survival < 30%), better for lymphomas and sarcomas, and best for carcinoid tumors. There has been no significant change in long-term survival rates for any of the 4 histological subtypes. Currently, with the possible exceptions of obesity and cigarette smoking, there are no established modifiable risk factors which might provide the foundation for a prevention program aimed at reducing the incidence and mortality of cancers of the small intestine. More research with better quality and sufficient statistical power is needed to get better understanding of the etiology and biology of this cancer. In addition, more studies should be done to assess not only exposures of interest, but also host susceptibility.

Breast cancer risk associated with residential proximity to industrial plants in Canada.

OBJECTIVE: The relationship between breast cancer risk and residential proximity to paper mills, pulp mills, petroleum refineries, steel mills, thermal power plants, alum smelters, nickel smelters, lead smelters, copper smelters, and zinc smelters was assessed. METHODS: We conducted a population-based case-control study of 2343 cases with breast cancer and 2467 controls using residential proximity at some time between 1960 and 5 years before the completion of questionnaire in Canada. RESULTS: Adjusted odds ratios were statistically significantly increased for residing near steel mills (0.8 to 3.2 km) and thermal power plants (<0.8 km) in premenopausal women, petroleum refinery (0.8 to 3.2 km) and pulp mills (0.8 to 3.2 km) in postmenopausal women, and for 10 or more years of residing near thermal power plants of 0.8 km. CONCLUSIONS: Our preliminary results suggested possible weak associations between breast cancer and proximity to steel mills, pulp mills, petroleum refineries, and thermal power plants.

Increasing incidence in liver cancer in Canada, 1972-2006: Age-period-cohort analysis.

BACKGROUND/AIMS: Our study aimed to assess 1) the temporal trends in incidence and mortality of liver cancer and 2) age-period-cohort effects on the incidence in Canada. METHODS: We analyzed data obtained from the Canadian Cancer Registry Database and Canadian Vital Statistics Death Database. We first examined temporal trends by sex, age group, and birth cohort between 1972 and 2006. Three-year period rates and annual percentage change (APC) were calculated to compare the changes over the study period. We used age-period-cohort modelling to estimate underlying effects on the observed trends in incidence. RESULTS: The overall age-adjusted incidence rates increased from 2.6 and 1.5 per 100 000 in 1972-74 to 6.5 (APC: 2.9) and 2.2 (APC: 1.2) per 100 000 in 2004-06 among males and females, respectively. The age-adjusted mortality rates increased from 3.3 and 2.0 per 100 000 in 1972-74 to 6.0 (APC: 2.3) and 2.6 (APC: 1.2) per 100 000 in 2004-06 among males and females, respectively. The incidence increased most rapidly in men aged 45-54 years (APC: 4.1) and women aged 65-74 years (APC: 1.7) over the period of study. CONCLUSIONS: The age-period-cohort analysis suggests that birth-cohort effect is underlying the increase in incidence. While the exact reason for the increased incidence of liver cancer remains unknown, reported increase in HBV and HCV infections, and immigration from high-risk regions of the world may be important factors.

Physical activity and hematologic cancer prevention.

This chapter presents the epidemiologic evidence on the association between physical activity and hematologic cancers and related hypothesized biologic mechanisms. Some preliminary indications of a protective role for physical activity for non-Hodgkin's lymphoma, leukemia, multiple myeloma, and Hodgkin's lymphoma exist, but the level of epidemiologic evidence is still insufficient to make any definitive conclusions regarding the nature of these associations. Several plausible biologic mechanisms underlying the possible associations between physical activity and hematologic cancers have been proposed, including enhancement of immune function, reduction in obesity, improvement of antioxidant defense systems, impact on metabolic hormones, and anti-inflammatory effects. Future studies should improve the estimation of physical activity by using more reliable, valid, and comprehensive measurement tools, assessing all components of physical activity (type, intensity, and time period), and conducting intervention studies to evaluate the effect of physical activity on various biomarkers of cancer in order to provide further insight into plausible biologic mechanisms underlying the possible association between physical activity and hematologic cancers.

Energy intake, physical activity, energy balance, and cancer: epidemiologic evidence.

Energy intake, physical activity, and obesity are modifiable lifestyle factors. This chapter reviews and summarizes the epidemiologic evidence on the relation of energy intake, physical activity, and obesity to cancer. High energy intake may increase the risk of cancers of colon-rectum, prostate (especially advanced prostate cancer), and breast. However, because physical activity, body size, and metabolic efficiency are highly related to total energy intake and expenditure, it is difficult to assess the independent effect of energy intake on cancer risk. There are sufficient evidences to support a role of physical activity in preventing cancers of the colon and breast, whereas the association is stronger in men than in women for colon cancer and in postmenopausal than in premenopausal women for breast cancer. The evidence also suggests that physical activity likely reduces the risk of cancers of endometrium, lung, and prostate (to a lesser extent). On the other hand, there is little or no evidence that the risk of rectal cancer is related to physical activity, whereas the results have been inconsistent regarding the association between physical activity and the risks of cancers of pancreas, ovary and kidney. Epidemiologic studies provide sufficient evidence that obesity is a risk factor for both cancer incidence and mortality. The evidence supports strong links of obesity with the risk of cancers of the colon, rectum, breast (in postmenopausal women), endometrium, kidney (renal cell), and adenocarcinoma of the esophagus. Epidemiologic evidence also indicates that obesity is probably related to cancers of the pancreas, liver, and gallbladder, and aggressive prostate cancer, while it seems that obesity is not associated with lung cancer. The role of obesity in other cancer risks is unclear.