Potential causal links of long-term air pollution with lung cancer incidence: From the perspectives of mortality and hospital admission in a large cohort study in southern China

Evidence on the potential causal links of long-term air pollution exposure with lung cancer incidence (reflected by mortality and hospital admission) was limited, especially based on large cohorts. We examined the relationship between lung cancer and long-term exposure to particulate matter (PM, including PM_2.5, PM₁₀ and PM_10-2.5) and nitrogen dioxide (NO₂) among a large cohort of general Chinese adults using causal inference approaches. The study included 575 592 participants who were followed up for an average of 8.2 years. The yearly exposure of PM and NO₂ was estimated through satellite-based random forest approaches and the ordinary kriging method, respectively. Marginal structural Cox models were used to examine hazard ratios (HRs) of mortality and hospital admission due to lung cancer following air pollution exposure, adjusting for potential confounders. The HRs of mortality due to lung cancer were 1.042 (95% confidence interval [CI]: 1.033-1.052), 1.032 (95% CI:1.024-1.041) and 1.052 (95% CI:1.041-1.063) for each 1 μg/m³ increase in PM_2.5, PM₁₀ and NO₂, respectively. In addition, we observed statistically significant effects of PMs on hospital admission due to lung cancer. The HRs (95%CI) were 1.110 (1.027-1.201), 1.067 (1.020-1.115) and 1.079 (1.010-1.153) for every 1 μg/m³ increase in PM_2.5, PM₁₀, PM_10-2.5, respectively. Furthermore, we found larger effect estimates among the elderly and those who exercised more frequently. We provided the most comprehensive evidence of the potential causal links between two outcomes of lung cancer and long-term air pollution exposure. Relevant policies should be developed, with special attention to protecting the vulnerable groups of the population.     

The effect of atmospheric particulate matter on survival of breast cancer among US females

Short-term effects of ambient particulate matter (PM) on cardiopulmonary morbidity and mortality have been consistently documented. However, no study has investigated its long-term effects on breast cancer survival. We selected all female breast cancer cases (n = 255,128) available in the California Surveillance Epidemiology and End Results cancer data. These cases were linked to 1999–2009 California county-level PM daily monitoring data. We examined the effect of PM on breast cancer survival. Results from Kaplan–Meier survival analysis show that female breast cancer cases living in areas with higher levels of PM₁₀ and PM_2.5 had a significant shorter survival than those living in areas with lower exposures (p < 0.0001). The results from marginal cox proportional hazards models suggest that exposure to higher PM₁₀ (HR 1.13, 95 % CI 1.02–1.25, per 10 μg/m³) or PM_2.5 (HR 1.86, 95 % CI 1.12–3.10, per 5 μg/m³) was significantly associated with early mortality among female breast cancer cases after adjusting for individual-level covariates such as demographic factors, cancer stage and year diagnosed, and county-level covariates such as socioeconomic status and accessibility to medical resources. Interactions between cancer stage and PM were also observed; the effect of PM on survival was more pronounced among individuals diagnosed with early stage cancers. This study suggests that exposure to high levels of PM may have deleterious effects on the length of survival from breast cancer, particularly among women diagnosed with early stage cancers. The findings from this study warrant further investigation.     

Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor air pollution at the residence and the incidence of kidney parenchyma cancer in the general population. We used data from 14 European cohorts from the ESCAPE study. We geocoded and assessed air pollution concentrations at baseline addresses by land‐use regression models for particulate matter (PM₁₀, PM_2.5, PM_coarse, PM_2.5 absorbance (soot)) and nitrogen oxides (NO₂, NO_x ), and collected data on traffic. We used Cox regression models with adjustment for potential confounders for cohort‐specific analyses and random effects models for meta‐analyses to calculate summary hazard ratios (HRs). The 289,002 cohort members contributed 4,111,908 person‐years at risk. During follow‐up (mean 14.2 years) 697 incident cancers of the kidney parenchyma were diagnosed. The meta‐analyses showed higher HRs in association with higher PM concentration, e.g. HR = 1.57 (95%CI: 0.81–3.01) per 5 μg/m³ PM_2.5 and HR = 1.36 (95%CI: 0.84–2.19) per 10^?5m^?1 PM_2.5 absorbance, albeit never statistically significant. The HRs in association with nitrogen oxides and traffic density on the nearest street were slightly above one. Sensitivity analyses among participants who did not change residence during follow‐up showed stronger associations, but none were statistically significant. Our study provides suggestive evidence that exposure to outdoor PM at the residence may be associated with higher risk for kidney parenchyma cancer; the results should be interpreted cautiously as associations may be due to chance.     

Air pollution and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts for Air Pollution Effects (ESCAPE)

Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancers of the stomach and upper aerodigestive tract (UADT). We investigated the association of long‐term exposure to ambient air pollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land‐use regression models for particulate matter (PM) below 10 µm (PM₁₀), below 2.5 µm (PM_2.5), between 2.5 and 10 µm (PM_coarse), PM_2.5 absorbance and nitrogen oxides (NO₂ and NO_X) as well as approximated by traffic indicators. Cox regression models with adjustment for potential confounders were used for cohort‐specific analyses. Combined estimates were determined with random effects meta‐analyses. During average follow‐up of 14.1 years of 305,551 individuals, 744 incident cases of gastric cancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5 µg/m³ of PM_2.5 was 1.38 (95% CI 0.99; 1.92) for gastric and 1.05 (95% CI 0.62; 1.77) for UADT cancers. No associations were found for any of the other exposures considered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influence markedly the effect estimate for PM_2.5 and gastric cancer. Higher estimated risks of gastric cancer associated with PM_2.5 was found in men (HR 1.98 [1.30; 3.01]) as compared to women (HR 0.85 [0.5; 1.45]). This large multicentre cohort study shows an association between long‐term exposure to PM_2.5 and gastric cancer, but not UADT cancers, suggesting that air pollution may contribute to gastric cancer risk.     

Long‐term exposure to fine particulate matter air pollution and the risk of lung cancer among participants of the Canadian National Breast Screening Study

Recently, air pollution has been classified as a carcinogen largely on the evidence of epidemiological studies of lung cancer. However, there have been few prospective studies that have evaluated associations between fine particulate matter (PM_2.5) and cancer at lower concentrations. We conducted a prospective analysis of 89,234 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM_2.5 could be assigned. The cohort was linked to the Canadian Cancer Registry to identify incident lung cancers through 2004. Surface PM_2.5 concentrations were estimated using satellite data. Cox proportional hazards models were used to characterize associations between PM_2.5 and lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual‐level characteristics, including smoking. The cohort was composed predominantly of Canadian‐born (82%), married (80%) women with a median PM_2.5 exposure of 9.1 µg/m³. In total, 932 participants developed lung cancer. In fully adjusted models, a 10 µg/m³ increase in PM_2.5 was associated with an elevated risk of lung cancer (HR: 1.34; 95% CI = 1.10, 1.65). The strongest associations were observed with small cell carcinoma (HR: 1.53; 95% CI = 0.93, 2.53) and adenocarcinoma (HR: 1.44; 95% CI = 1.06, 1.97). Stratified analyses suggested increased PM_2.5 risks were limited to those who smoked cigarettes. Our findings are consistent with previous epidemiological investigations of long‐term exposure to PM_2.5 and lung cancer. Importantly, they suggest associations persist at lower concentrations such as those currently found in Canadian cities.     

Insights into synchronous peritoneal metastases from hepatobiliary origin: Incidence,risk factors,treatment, and survival from a nationwide database

Introduction– This population-based study aimed to investigate incidence, risk factors, treatment, and survival of synchronous peritoneal metastases (PM) of hepatobiliary origin.Methods– All Dutch patients diagnosed with hepatobiliary cancer between 2009 and 2018 were selected. Factors associated with PM were identified with logistic regression analyses. Treatments for patients with PM were categorized into local therapy, systemic therapy, and best supportive care (BSC). Overall survival (OS) was investigated using log-rank test.Results– In total, 12 649 patients were diagnosed with hepatobiliary cancer of whom 8% (n = 1066) were diagnosed with synchronous PM (12% [n = 882/6519] in biliary tract cancer [BTC] vs. 4% [n = 184/5248] in hepatocellular carcinoma [HCC]). Factors that were positively associated with PM were the female sex (OR 1.18, 95% CI 1.03–1.35), BTC (OR 2.93, 95% CI 2.46–3.50), diagnosis in more recent years (2013–2015: OR 1.42, 95% CI 1.20–1.68; 2016–2018: OR 1.48, 95% CI 1.26–1.75), T3/T4 stage (OR 1.84, 95% CI 1.55–2.18), N1/N2 stage (OR 1.31, 95% CI 1.12–1.53) and other synchronous systemic metastases (OR 1.85, 95% CI 1.62–2.12). Of all PM patients, 723 (68%) received BSC only. Median OS was 2.7 months (IQR 0.9–8.2) in PM patients.Conclusion– Synchronous PM were found in 8% of all hepatobiliary cancer patients and occurred more often in BTC than in HCC. Most patients with PM received BSC only. Given the high incidence and dismal prognosis of PM patients, extended research in hepatobiliary PM is needed to achieve better outcome in these patients.     

Cardiovascular medication after cancer at a young age in Finland: A nationwide registry linkage study

Despite improved survival rates, childhood and young adult (YA) cancer survivors face elevated risks for life‐threatening morbidities, especially cardiovascular complications. Our nationwide Finnish registry study investigated the purchases of cardiovascular medication from 1993 to 2011 in patients diagnosed with cancer aged below 35 years (N = 8,197) between 1993 and 2004 compared to siblings (N = 29,974) via linkage to the drug purchase registry. The cumulative incidence for purchasing cardiovascular medications was higher in childhood and YA cancer patients compared to siblings with a rising trend over time. After childhood cancer, the highest hazard ratio (HR) was found for purchasing anticoagulants (HR 19.8, 95% CI 8.5–45.9). The HRs for any cardiovascular medication (HR 7.2, 95% CI 5.1–10.1) and cardiac medication (HR 4.8, 95% CI 3.3–6.9) were markedly elevated after childhood cancer as well. Regarding YA cancer patients, the respective HRs were 2.5 (95% CI 2.0–3.2) for anticoagulants, HR 1.7 (95% CI 1.5–1.9) for any cardiovascular medication and HR 1.5 (95% CI 1.3–1.7) for cardiac medication. Among cancer patients, highest HRs for cardiovascular medication were observed after childhood acute lymphoblastic leukemia (ALL) and bone tumors (HR 10.2, 95% CI 6.8–15.5 and HR 7.4, 95% CI 4.0–13.7) and YA ALL and acute myeloid leukemia (HR 5.1, 95% CI 3.5–7.1 and HR 2.8, 95% CI 1.8–4.0). Our study demonstrated increased HRs for purchasing cardiovascular medication after early‐onset cancer compared to siblings reflecting elevated cardiovascular morbidity. Thus, the implementation of long‐term cardiovascular disease screening is imperative to prevent, detect and adequately treat cardiovascular late effects after cancer at a young age.     

Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses’ health study and health professionals follow‐up study

Although experimental evidence suggests calcium‐sensing receptor (CASR) as a tumor‐suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow‐up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer‐specific and all‐cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE‐1 methylation level, expressions of PTGS2, VDR and CTNNB1 and mutations of KRAS, BRAF and PIK3CA. There were 240 colorectal cancer‐specific deaths and 427 all‐cause deaths. The median follow‐up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared with patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer‐specific mortality were 0.80 [95% confidence interval (CI): 0.55–1.16] in patients with moderate CASR expression and 0.50 (95% CI: 0.32–0.79) in patients with intense CASR expression (p‐trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64–1.13) and 0.81 (0.58–1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer‐specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression.     

Insurance status and survival disparities among nonelderly rectal cancer patients in the National Cancer Data Base

BACKGROUND:

Among patients with colorectal cancer, insurance status is associated with disparities in survival as well as differences in stage and treatment. The role of stage and treatment differences in these survival disparities is not clear because insurance status is also strongly correlated with race/ethnicity, socioeconomic status, and other factors.

METHODS:

The authors used data from the National Cancer Data Base, a national hospital‐based cancer registry, to examine insurance status and other factors related to survival among 19,154 rectal cancer patients aged 18 to 64 years. The authors examined the impact of 10 factors on 5‐year survival: age, sex, race/ethnicity, histologic grade, histologic subtype, neighborhood education and income levels, facility type, stage, and treatment.

RESULTS:

Adjusted only for age, the hazard ratio (HR) for death at 5 years was 1.00 (referent) among privately insured patients, 2.05 (95% confidence interval [CI], 1.89‐2.23) among Medicaid‐insured patients, and 2.01 (95% CI, 1.84‐2.19) among uninsured patients. After adjustment for all factors other than stage and treatment, the HRs were 1.88 (95% CI, 1.722.04) for Medicaid‐insured patients and 1.84 (95% CI, 1.69‐2.01) for uninsured patients. After further adjustment for stage and treatment, the HRs were 1.34 (95% CI, 1.22‐1.46) for Medicaid‐insured patients and 1.29 (95% CI, 1.18‐1.42) for uninsured patients.

CONCLUSIONS:

After adjustment for age, further adjustment for 9 other factors reduced the excess mortality among rectal cancer patients without private insurance by approximately 70%. Disparities in stage and treatment accounted for approximately 53% of the excess mortality, whereas factors other than stage and treatment accounted for approximately 17%. Cancer 2010. © 2010 American Cancer Society.     

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM_2.5) levels on LC in Taiwan, in relation to contrasting PM_2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

Association between ambient air pollution and breast cancer risk: The multiethnic cohort study

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NO_x, NO₂, PM₁₀, PM_2.5), land use regression (LUR, NO_x, NO₂) and California Line Source Dispersion model (CALINE4, NO_x, PM_2.5) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993–1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NO_x (per 50 parts per billion [ppb]) and NO₂ (per 20 ppb) determined by kriging and LUR and with PM_2.5 and PM₁₀ (per 10 μg/m³) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NO_x (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02–1.79), NO₂ (HR = 1.44, 95% CI: 1.04–1.99), PM₁₀ (HR = 1.29, 95% CI: 1.07–1.55) and PM_2.5 (HR = 1.85, 95% CI: 1.15–2.99) determined by kriging and NO_x (HR = 1.21, 95% CI:1.01–1.45) and NO₂ (HR = 1.26, 95% CI: 1.00–1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NO_x and NO₂ among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted.     

Prognosis following cancer surgery during holiday periods

Surgery is the mainstay curative treatment in most cancer. We aimed to test the new hypothesis that cancer surgery performed during holiday periods is associated with worse long‐term prognosis than for non‐holiday periods. This nationwide Swedish population‐based cohort study included 228,927 patients during 1997–2014 who underwent elective resectional surgery for a cancer where the annual number of resections was over 100. The 16 eligible cancer sites were grouped into 10 cancer groups. The exposure, holiday periods, was classified as wide (14‐weeks) or narrow (7‐weeks). Surgery conducted inside versus outside holiday periods was compared regarding overall disease‐specific (main outcome) and overall all‐cause (secondary outcome) mortality. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, sex, comorbidity, hospital volume, calendar period and tumor stage. Surgery conducted during wide and narrow holiday periods were associated with increased HRs of disease‐specific mortality for cancer of the breast (HR 1.08, 95% CI 1.03–1.13 and HR 1.06, 95% CI 1.01–1.12) and possibly of cancer of the liver‐pancreas‐bile ducts (HR 1.09, 95% CI 0.99–1.20 and HR 1.12, 95% CI 0.99–1.26). Sub‐groups with cancer of the colon‐rectum, head‐and‐neck, prostate, kidney‐urine bladder and thyroid also experienced statistically significantly worse prognosis following surgery conducted during holiday periods. No influence of surgery during holiday was detected for cancer of the esophagus‐stomach, lung or ovary‐uterus. All‐cause HRs were similar to the disease‐specific HRs. The prognosis following cancer surgery might not be fully maintained during holiday periods for all cancer sites.     

Association between metformin use after surgery for colorectal cancer and oncological outcomes: A nationwide register‐based study

Colorectal cancer is one of the most common malignancies in the Western world, and even after surgical removal, there is a high recurrence rate. Metformin treatment has been associated with a reduced risk of developing cancer, but whether metformin influences the risk of recurrence is unknown. The aim of our study was to examine the association between treatment with metformin and recurrence‐free, disease‐free survival and all‐cause mortality after surgery for colorectal cancer. The study was an observational register‐based study and included 25,785 patients, of which 1,116 had medically treated diabetes and 966 started metformin treatment at some point postoperatively. Diabetes was not associated with neither disease‐free (HR_adjusted = 1.09, 95% CI 0.97–1.21, p = 0.15) nor recurrence‐free survival (HR_adjusted = 1.13, 95% CI 0.95–1.35, p = 0.17). The study found no difference in regards to disease‐free or recurrence‐free survival between the metformin treated group (HR_RFS = 1.06, 95% CI 0.87–1.15, p = 0.57, HR_DFS = 1.01, 95% CI 0.89–1.15, p = 0.85) and non‐diabetic patients. Patients with diabetes had increased all‐cause mortality (HR_adjusted = 1.29, 95% CI 1.16–1.45, p < 0.0001). Metformin treatment did not affect all‐cause mortality (HR = 1.07, 95% CI 0.94–1.22, p = 0.33) compared to non‐diabetic patients. In conclusion, our study did not find an association between diabetes or metformin treatment and recurrence‐free or disease‐free survival after surgery for colorectal cancer. However, diagnosis of diabetes is associated with increased all‐cause mortality.     

Annual hospital volume of surgery for gastrointestinal cancer in relation to prognosis

BackgroundStudies examining hospital volume for surgery for various gastrointestinal (GI) cancer types have shown conflicting results regarding the influence on long-term prognosis. The aim of this study was to examine annual hospital volume in relation to long-term survival after elective surgery for all GI cancers (esophagus, stomach, liver, pancreas, bile ducts, small bowel, colon, and rectum).MethodsPopulation-based cohort study including all 45,908 patients who underwent elective surgery for GI cancers in Sweden in 2005–2013. Follow-up was until 2016 for disease-specific 5-year mortality (main outcome) and 2018 for all-cause 5-year mortality (secondary outcome). Hospitals were divided into quartiles for each GI cancer according to a 4-year average annual volume of the year of surgery and three years earlier. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for relevant confounders.ResultsHigher hospital volume was associated with a survival benefit in the large group of patients (n = 26,688) who underwent colon cancer resection, with HR 0.89 (95% CI 0.84–0.96) for disease-specific 5-year mortality comparing the highest with the lowest quartile. Higher hospital volume improved 5-year mortality in sub-groups of patients who underwent surgery for cancer of the esophagus, pancreas, and rectum. No such improvements were found for cancer of the stomach, liver, bile ducts, or small bowel.ConclusionLong-term survival was improved at higher volume hospitals for some GI cancers (colon, esophagus, pancreas, rectum), but not for others (stomach, liver, bile ducts, small bowel).     

Obesity,diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients

BackgroundTo determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy.Patients and methodsWe identified 6342 patients with stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status.ResultsIn a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02–1.36], 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively.ConclusionsIn patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.     

Type 2 diabetes and colorectal cancer survival: The multiethnic cohort

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre‐existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all‐cause and 678 CRC‐specific deaths after a mean follow‐up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC‐specific and all‐cause survival while adjusting for known confounders. Overall, CRC‐specific survival was not associated with pre‐existing T2D (HR = 0.84; 95% CI = 0.67–1.07). However, a significant interaction was seen for comorbidity (p_interaction = 0.03) with better survival among those without pre‐existing conditions (HR = 0.49; 95% CI = 0.25–0.96) while no association was seen in patients with comorbid conditions. All‐cause mortality was also not related to pre‐existing T2D (HR = 1.11; 95% CI = 0.98–1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19–1.56). Stratification by T2D duration suggested higher CRC‐specific and all‐cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre‐existing T2D had no influence on disease‐specific and all‐cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.     

Prognostic value of phospho‐Akt in patients with non‐small cell lung carcinoma: A meta‐analysis

Previous studies have been inconsistent with respect to the reported associations between phospho‐Akt (p‐Akt) overexpression and lung cancer prognosis. In this study, we conducted a systematic review and meta‐analysis to assess the prognostic value of p‐Akt in patients with non‐small cell lung carcinoma (NSCLC). Relevant articles were identified by searching MEDLINE. Hazard risks (HRs) from individual studies were calculated and pooled by using a random‐effect model, and heterogeneity and publication bias analyses were also performed. Finally, 18 studies comprising 2,353 patients were included in the meta‐analysis. p‐Akt overexpression was associated with worse survival in NSCLC patients, and the pooled HRs for all the studies was 1.38 (95% confidence interval [CI]: 1.11–1.70; p < 0.01). After subgroup analysis, the association was strengthened in the surgery treatment group, with an HR of 1.44 (95% CI: 1.19–1.75; p < 0.01), while in the tyrosine kinase inhibitors treatment group, the statistical significance disappeared (HR: 1.22, 95% CI: 0.70–2.14; p = 0.48). The HR in cases of early stage disease (I–III) was 1.35 (95% CI: 1.08–1.69; p = 0.04); however, in cases of late stage disease (III–IV), the association became non‐significant (HR: 1.22, 95% CI: 0.64–2.33; p = 0.54). Our results suggest that there was a significantly inverse association between p‐Akt overexpression and the prognosis of NSCLC patients, and that this association appeared to be limited in early‐stage patients who underwent surgery.     

Prospective associations of depression with survival: a population-based cohort study in patients with newly diagnosed breast cancer

Psychological factors may influence survival in breast cancer patients but results of previous research are inconclusive. This prospective population-based study tested whether depression predicts mortality in breast cancer patients. Routinely collected depression screening data were merged with electronically archived provincial cancer registry data and censored data from British Columbia Vital Statistics (extracted in December 2012). Cox proportional-hazards regression analyses were conducted to predict all-cause and breast cancer-specific mortality as a function of depression after controlling for biomedical confounders. Of 1,646 patients, 1,604 had breast cancer stages I–III and 42 had stage IV breast cancer. 176 (11.0 %) versus 28 (66.7 %) were deceased after a median follow-up of 76 months. In patients with curable breast cancer, depression predicted all-cause (HR = 1.54 (95 % CI 1.06–2.25); p = 0.024), but not breast cancer-specific mortality (HR = 1.51 (95 % CI 0.95–2.41); p = 0.084). No association was shown for metastatic disease. Stage-specific analyses demonstrated a 2–2.5-fold increase in breast cancer-specific and all-cause mortality in patients with stage I and II disease, but not in patients with stage III or IV breast cancer. In stage I breast cancer patients, age moderated effects of depression such that depressed younger patients diagnosed at age 45 (i.e., mean age ?1SD) showed a ninefold (HR = 9.82 (95 % CI 2.26–42.68); p = 0.002) increase in all-cause mortality and depressed patients at 57 a 3.7-fold (HR = 3.69 (95 % CI 1.44–9.48); p = 0.007) increase, while no association was evident in older patients at age 69 (mean age +1SD). Depression is strongly associated with mortality in younger patients with early stage breast cancer.     

Ambient PM<Subscript>2.5</Subscript> air pollution exposure and hepatocellular carcinoma incidence in the United States

Purpose

To conduct the first epidemiologic study prospectively examining the association between particulate matter air pollution?<?2.5 µm in diameter (PM_2.5) exposure and hepatocellular carcinoma (HCC) risk in the U.S.

Methods

Surveillance, Epidemiology, and End Results (SEER) provided information on HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries across the U.S. Ambient PM_2.5 exposure was estimated by linking the SEER county with a spatial PM_2.5 model using a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios and 95% confidence intervals (CIs) for the association between ambient PM_2.5 exposure per 10 µg/m³ increase and HCC risk adjusting for individual-level age at diagnosis, sex, race, year of diagnosis, SEER registry, and county-level information on health conditions, lifestyle, demographic, socioeconomic, and environmental factors.

Results

Higher levels of ambient PM_2.5 exposure were associated with a statistically significant increased risk for HCC (n?=?56,245 cases; adjusted IRR per 10 µg/m³ increase?=?1.26, 95% CI 1.08, 1.47; p?<?0.01).

Conclusions

If confirmed in studies with individual-level PM_2.5 exposure and risk factor information, these results suggest that ambient PM_2.5 exposure may be a risk factor for HCC in the U.S.