STK15 rs2273535 polymorphism and cancer risk: A meta-analysis of 74,896 subjects

Background: It has been suggested that the serine/threonine kinase 15 (STK15) T91A rs2273535 polymorphism is associated with susceptibility to cancer. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. Methods: PubMed was searched to select studies. Case–control studies containing available genotype frequencies of the STK15 rs2273535 polymorphism were chosen, and the odds ratio (OR) with its 95% confidence interval (CI) was utilized to assess the strength of association. Results: 52 studies – including 34,057 cases and 40,839 controls – were identified. A significant effect of the STK15 rs2273535 polymorphism on cancer risk was found (AA vs. TT: OR = 1.13, 95%CI = 1.01–1.26, P_{heterogeneity} < 0.001; AA vs. TA/TT: OR = 1.12, 95%CI = 1.02–1.22, P_{heterogeneity} < 0.001; TA/AA vs. TT: OR = 1.06, 95%CI = 1.01–1.12, P_{heterogeneity} < 0.001). Stratified analysis by cancer type revealed that the STK rs2273535 polymorphism may contribute to the risk of breast cancer (AA vs. TT: OR = 1.21, 95%CI = 1.01–1.44, P_{heterogeneity} = 0.002), colorectal cancer (AA vs. TA/TT: OR = 1.24, 95%CI = 1.05–1.47, P_{heterogeneity} = 0.124), and esophageal cancer (AA vs. TA/TT: OR = 1.19, 95%CI = 1.02–1.39, P_{heterogeneity} = 0.148). Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (AA vs. TA/TT: OR = 1.20, 95%CI = 1.05–1.37, P_{heterogeneity} = 0.004). Conclusion: This meta-analysis suggests that the STK15 rs2273535 polymorphism is a candidate gene polymorphism for cancer susceptibility, especially in Asian populations.     

Incidencia de cáncer de tiroides en la provincia de Neuquén,período 2001-2012

During the past decades, an increasing incidence of thyroid cancer (TC) has been reported worldwide. In Argentina there is no national cancer registry, and its incidence has therefore not been established. The aim of our study was to determine the incidence of TC in the province of Neuquén and to compare it to that reported in the literature. The medical records of 229 patients admitted over a period of 12 years (2001 to 2012) were used for data analysis.Tumor size, age, sex, and histological type were evaluated. The study period was divided into four three-year periods, and differences in each of these features were analyzed. We found an incidence of 4.72/100,000 inhabitants/year, and almost all patients had papillary TC. TC was five times more common in females as compared to males (7.78 and 1.55 respectively). Mean tumor size was 22.2 ± 1.1 mm. Tumor size was significantly greater in men (31.8 ± 3.7 mm) than in women (20.4 ± 1.0 mm). When grouped by three-year periods, a higher number of cases was found in the last one (47, 49, 49 and 84 respectively). As regards tumor distribution by size, there was a significant decrease in mean tumor size in the fourth period and an increase in the proportion of tumors <10 mm.We report an increase in TC incidence in the Argentinean province of Neuquén which is similar to the overall increase reported in the international literature.     

Obesity,physical activity and cancer risks: Results from the Cancer,Lifestyle and Evaluation of Risk Study (CLEAR)

IntroductionPhysical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers.MethodsWe estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression.ResultsFor women, BMI was positively associated with UC risk; specifically, obese women (BMI ≥30 kg/m²) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (<25 kg/m²) (OR = 1.99;CI:1.31–3.03). For men, BMI was also positively associated with the risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR = 1.37;CI:1.11–1.70), 113% (OR = 2.13;CI:1.55–2.91) and 51% (OR = 1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMI<25 kg/m²).Among women, PA was inversely associated with the risks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR = 0.60;CI:0.44–0.84) and UC (OR = 0.47;CI:0.27–0.80). Reduced risks of BC were associated with low (OR = 0.66;CI:0.51–0.86) and moderate (OR = 0.72;CI:0.57–0.91) levels of PA. There was no association between PA levels and cancer risks for men.We found no evidence of an interaction between BMI and PA in the CLEAR study.ConclusionThese findings suggest that PA and obesity are independent cancer risk factors.     

Improving cancer patient emergency room utilization: A New Jersey state assessment

IntroductionDue to its increasing incidence and its major contribution to healthcare costs, cancer is a major public health problem in the United States. The impact across different services is not well documented and utilization of emergency departments (ED) by cancer patients is not well characterized. The aim of our study was to identify factors that can be addressed to improve the appropriate delivery of quality cancer care thereby reducing ED utilization, decreasing hospitalizations and reducing the related healthcare costs.MethodsThe New Jersey State Inpatient and Emergency Department Databases were used to identify the primary outcome variables; patient disposition and readmission rates. The independent variables were demographics, payer and clinical characteristics. Multivariable unconditional logistic regression models using clinical and demographic data were used to predict hospital admission or emergency department return.ResultsA total of 37,080 emergency department visits were cancer related with the most common diagnosis attributed to lung cancer (30.0%) and the most common presentation was pain. The disposition of patients who visit the ED due to cancer related issues is significantly affected by the factors of race (African American OR = 0.6, p value = 0.02 and Hispanic OR = 0.5, p value = 0.02, respectively), age aged 65 to 75 years (SNF/ICF OR 2.35, p value = 0.00 and Home Healthcare Service OR 5.15, p value = 0.01, respectively), number of diagnoses (OR 1.26, p value = 0.00), insurance payer (SNF/ICF OR 2.2, p value = 0.02 and Home Healthcare Services OR 2.85, p value = 0.07, respectively) and type of cancer (breast OR 0.54, p value = 0.01, prostate OR 0.56, p value = 0.01, uterine OR 0.37, p value = 0.02, and other OR 0.62, p value = 0.05, respectively). In addition, comorbidities increased the likelihood of death, being transferred to SNF/ICF, or utilization of home healthcare services (OR 1.6, p value = 0.00, OR 1.18, p value = 0.00, and OR 1.16, p value = 0.04, respectively). Readmission is significantly affected by race (American Americans OR 0.41, standard error 0.08, p value = 0.001 and Hispanics OR 0.29, standard error 0.11, p value = 0.01, respectively), income (Quartile 2 OR 0.98, standard error 0.14, p value 0.01, Quartile 3 OR 1.07, standard error 0.13, p value 0.01, and Quartile 4 OR 0.88, standard error 0.12, p value 0.01, respectively), and type of cancer (prostate OR 0.25, standard error 0.09, p value = 0.001).ConclusionWeb based symptom questionnaires, patient navigators, end of life nursing and clinical cancer pathways can identify, guide and prompt early initiation of treat before progression of symptoms in cancer patients most likely to visit the ED. Thus, improving cancer patient satisfaction, outcomes and reduce health care costs.     

Associations of body mass index with cancer incidence among populations,genders, and menopausal status: A systematic review and meta-analysis

In order to further reveal the differences of association between body mass index (BMI) and cancer incidence across populations, genders, and menopausal status, we performed comprehensive meta-analysis with eligible citations. The risk ratio (RR) of incidence at 10 different cancer sites (per 5 kg/m² increase in BMI) were quantified separately by employing generalized least-squares to estimate trends, and combined by meta-analyses. We observed significantly stronger association between increased BMI and breast cancer incidence in the Asia⿿Pacific group (RR 1.18:1.11⿿1.26) than in European⿿Australian (1.05:1.00⿿1.09) and North-American group (1.06:1.03⿿1.08) (meta-regression p < 0.05). No association between increased BMI and pancreatic cancer incidence (0.94:0.71⿿1.24) was shown in the Asia⿿Pacific group (meta-regression p < 0.05), whereas positive associations were found in other two groups. A significantly higher RR in men was found for colorectal cancer in comparison with women (meta-regression p < 0.05). Compared with postmenopausal women, premenopausal women displayed significantly higher RR for ovarian cancer (pre- vs. post- = 1.10 vs. 1.01, meta-regression p < 0.05), but lower RR for breast cancer (pre- vs. post- = 0.99 vs. 1.11, meta-regression p < 0.0001). Our results indicate that overweight or obesity is a strong risk factor of cancer incidence at several cancer sites. Genders, populations, and menopausal status are important factors effecting the association between obesity and cancer incidence for certain cancer types.     

Comparative incidence of cancer in HIV-AIDS patients and transplant recipients

BackgroundStudies have found a relationship between decreased immunity and increased incidence of cancer.MethodsA systematic review of observational studies evaluating the incidence of cancer in both organ recipients and people with HIV/AIDS compared with the general population. Eligible studies were searched up to March 2011 in the following databases: Pubmed, Embase, Scielo, Cancerlit and Google scholar. In this study, the standardized incidence ratios (SIR) of cancer in people with HIV/AIDS and of organ transplant recipients were compared with those found among the general population.ResultsTwenty-five studies of transplant and HIV-associated cancer risk, involving 866 776 people with HIV/AIDS or organ recipients and 21 260 new cases of cancer, were included. The risk for the development of new cancer cases was higher among people with HIV/AIDS (SIR = 4, IC95% 3.78–4.24) and who received organs (SIR = 3.28, IC95% 3.06–3.52) when compared with the general population.ConclusionSimilar SIR in both immunocompromised populations suggests that the weakened immune system is responsible for the increased risk of new cases of cancer among these groups. Research investments are needed to develop effective cancer prevention strategies in these populations.     

Unstaged cancer in a population-based registry: Prevalence,predictors and patient prognosis

Purpose: Information on cancer stage at diagnosis is critical for population studies investigating cancer care and outcomes. Few studies have examined the factors which impact (1) staging or (2) outcomes for patients who are registered as having unknown stage. This study investigated (1) the prevalence of unknown stage at diagnosis on the New Zealand Cancer Registry (NZCR); (2) explored factors which predict unknown stage; (3) described receipt of surgery and (4) survival outcomes for patients with unknown stage. Methods: Patients diagnosed with the most prevalent 18 cancers between 2006 and 2008 (N = 41,489) were identified from the NZCR, with additional data obtained from mortality and hospitalisation databases. Logistic and Cox regression were used to investigate predictors of unknown stage and patient outcomes. Results: (1) Three distinct groups of cancers were found based on proportion of patients with unknown stage (low = up to 33% unknown stage; moderate = 33–64%; high = 65%+). (2) Increasing age was a significant predictor of unknown stage (adjusted odds ratios [ORs]: 1.18–1.24 per 5-year increase across groups). Patients with substantive comorbidity were more likely to have unknown stage but only for those cancers with a low (OR = 2.65 [2.28–3.09]) or moderate (OR = 1.17 [1.03–1.33]) proportion of patients with unknown stage. (3) Patients with unknown stage were significantly less likely to have received definitive surgery than those with local or regional disease across investigated cancers. (4) Patients with unknown stage had 28-day and 1-year survival which was intermediate between regional and distant disease. Discussion: We found that stage completeness differs widely by cancer site. In many cases, the proportion of unknown stage on a population-based register can be explained by patient, service and/or cancer related factors.     

Fallout from the Chernobyl accident and overall cancer incidence in Finland

Aim: We studied whether incidence of all cancer sites combined was associated with the radiation exposure due to fallout from the Chernobyl accident in Finland. An emphasis was on the first decade after the accident to assess the suggested “promotion effect”. Methods: The segment of Finnish population with a stable residence in the first post-Chernobyl year (2 million people) was studied. The analyses were based on a 250 m × 250 m grid squares covering all of Finland and all cancer cases except cancers of the breast, prostate and lung. Cancer incidence in four exposure areas (based on first-year dose due to external exposure <0.1 mSv, 0.1–1.3, 0.3–0.5, or ≥0.5 mSv) was compared before the Chernobyl accident (1981–1985) and after it (1988–2007) taking into account cancer incidence trends for a longer period prior to the accident (since 1966). Results: There were no systematic differences in the cancer incidence in relation to radiation exposure in any calendar period, or any subgroup by sex or age at accident. Conclusion: The current large and comprehensive cohort analysis of the relatively low levels of the Chernobyl fallout in Finland did not observe a cancer promotion effect.     

UDP-glucuronosyltransferase 2B17 genotype and the risk of lung cancer among Austrian Caucasians

Background: The enzyme uridine diphospho glucuronosyltansferase 2B17 (UGT2B17) glucuronidates several endogenous and exogenous compounds, including carcinogens from tobacco smoke like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanl (NNAL). UGT2B17 shows a remarkable copy number variation (CNV) and an association between deletion genotype and increased risk of lung adenocarcinoma in women has been previously reported. Methods: We investigated the UGT2B17 CNV by PCR in 453 Austrian lung cancer patients and in 449 healthy donors and analyzed the impact on lung cancer susceptibility and outcome. Results: Copy numbers of UGT2B17 were 44.4% (+/+), 42.2% (+/?) and 13.5% (?/?) in lung cancer patients and 43.0% (+/+), 46.3% (+/?) and 10.7% (?/?) among healthy donors. The null genotype was not significantly more frequent among women with adenocarcinoma compared to healthy women (p = 0.59). There was no association with overall survival (p = 0.622) and no significant sex-associated (p = 0.423) or histology-related impact on development of lung cancer. Conclusion: UGT2B17 deletion genotype was not associated with a significant risk for lung cancer development or outcome in our Central European patient cohort. Our study indicates that UGT2B17 is not a crucial factor in lung carcinogenesis among Caucasians and shows the importance of investigating such markers in large cohorts from different populations.     

Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study

BackgroundElevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl.MethodsWe conducted a population-based cohort study using data from Danish medical registries during 1998–2014. The study included 25,017 patients with a cancer diagnosis and Cbl levels of 200–600 pmol/L (reference/normal range), 601–800 pmol/L and >800 pmol/L measured up to one year prior to diagnosis, and a comparison cohort of 61,988 cancer patients without a plasma Cbl measurement. Patients treated with Cbl were excluded. Survival probability was assessed using Kaplan–Meier curves. Mortality risk ratios (MRR) were computed using Cox proportional hazard regression, adjusted for age, sex, calendar year, cancer stage and comorbidity, scored using the Charlson comorbidity index.ResultsSurvival probabilities were lower among patients with elevated Cbl levels than among patients with normal levels and among members of the comparison cohort [(1-year survival,%) Cbl: 200–600 pmol/L: 69.3%; 601–800 pmol/L: 49.6%; >800 pmol/L: 35.8%; comparison cohort: 72.6%]. Thirty-day mortality was elevated for patients with Cbl levels of 601–800 pmol/L or >800 pmol/L, compared to patients with levels of 200–600 pmol/L [(MRR (95% confidence interval): 601–800 pmol/L vs. 200–600 pmol/L: 1.9 (1.6–2.2); >800 pmol/L vs. 200–600 pmol/L: 2.7 (2.4–3.1)]. This association remained robust for 31–90-day and 91–365-day mortality, showing similar dose-response patterns.ConclusionCancer patients with elevated Cbl levels had higher mortality than those with normal Cbl levels. These findings may have clinical significance for assessing the prognosis of cancer patients.     

Second cancers following the diagnosis of Merkel cell carcinoma: A nationwide cohort study

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. MCCs and some other skin cancers, such as basal cell carcinomas, frequently harbour Merkel cell polyomavirus DNA. The purpose of the study was to investigate the frequency of second cancers following the diagnosis of MCC. We studied the incidence of second primary cancers after the diagnosis of MCC from the files of the Finnish Cancer Registry in 1979–2006. Among the 172 MCC patients identified a total of 34 second primary cancers were detected in 30 individuals after the diagnosis of MCC. Female MCC patients were diagnosed with 25 subsequent cancers (SIR, 2.35; 95% CI, 1.52–3.47; p < 0.001) and male patients with 9 cancers (SIR, 2.32, 95% CI, 1.06–4.40; p < 0.05). The MCC patients had an increased risk for a subsequent cancer (any site) compared to age-, gender- and calendar period-matched general population (standardized incidence ratio [SIR] 2.34; 95% confidence interval [CI], 1.62–3.27). The risks for basal cell carcinoma of the skin (O = 11), SIR, 3.48; 95% CI, 1.74–6.22 and chronic lymphocytic leukemia (O = 2), SIR, 17.9; 95% CI, 2.16–64.6 were significantly elevated. The SIRs for an overall second primary cancer risk did not change markedly with time since the diagnosis of MCC. We conclude that patients diagnosed with MCC have an increased risk for a second cancer. This risk may in part result from shared etiological factors between MCC and other tumour types, such as immunosuppression or possibly Merkel cell polyomavirus infection.     

Cancer cells resist hyperthermia due to its obstructed activation of caspase 3

AimIt is well known that inducing hyperthermia is a type of cancer treatment but some research groups indicate that this treatment is not effective. This article finds and explains the mechanism of this treatment and its possible problems.BackgroundHyperthermia is commonly known as a state when the temperature of the body rises to a level that can threaten one’s health. Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures (up to 45 °C). Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. However, this mechanism is not known.Materials and MethodsWe recently treated cancer cells with different temperatures ranging from 37 °C to 47 °C and further measured their caspase 3 secretion by ELISA, western blot and cell survival rate by microscope.ResultsWe found that most cancer cells are able to resist hyperthermia more than normal cells most likely via non-activation of caspase3. We also found that hyperthermia-treated (≥41°) cancer cells extend a long pseudopod-like extension in comparison to the same cancer cells under normal conditions.ConclusionOur data here indicates that cancer cells have resistance to higher temperatures compared to normal cells via non-activation of caspase 3. This is a significant issue that needs to be brought to attention as the medical community has always believed that a high temperature treatment can selectively kill cancer/tumor cells. Additionally, we believe that the pseudopod-like extensions of hyperthermia-treated cancer cells must be related to its resistance to hyperthermia.     

Hypoxia induced CA9 inhibitory targeting by two different sulfonamide derivatives including Acetazolamide in human Glioblastoma

HIF-1α regulated genes are mainly responsible for tumour resistance to radiation- and chemo-therapy. Among these genes, carbonic anhydrase isoform IX (CA9) is highly over expressed in many types of cancer especially in high grade brain cancer like Glioblastoma (GBM). Inhibition of the enzymatic activity by application of specific chemical CA9 inhibitor sulphonamides (CAI) like Acetazolamide (Aza.), the new sulfonamide derivative carbonic anhydrase inhibitor (SU.D2) or indirect inhibitors like the HIF-1α inhibitor Chetomin or molecular inhibitors like CA9-siRNA are leading to an inhibition of the functional role of CA9 during tumorigenesis. Human GBM cells were treated with in vitro hypoxia (1, 6, or 24 h at 0.1%, O₂). Aza. application was at a range between 250 and 8000 nM and the HIF-1α inhibitor Chetomin at a concentration range of 150–500 nM. Cell culture plates were incubated for 24 h under hypoxia (0.1% O₂). Further, CA9-siRNA constructs were transiently transfected into GBM cells exposed to extreme hypoxic aeration conditions. CA9 protein expression level was detectable in a cell-type specific manner under normoxic conditions. Whereas U87-MG exhibited a strong aerobic expression, U251 and U373 displayed moderate and GaMG very weak normoxic CA9 protein bands. Aza. as well as SU.D2 displayed inhibitory characteristics to hypoxia induced CA9 expression in the four GBM cell lines for 24 h of hypoxia (0.1% O₂) at concentrations between 3500 and 8000 nM, on both the protein and mRNA level. Parallel experiments using CA9-siRNA confirmed these results. Application of 150–500 nM of the glycolysis inhibitor Chetomin under similar oxygenation conditions led to a sharply reduced expression of both CA IX protein and CA9 mRNA levels, indicating a clear glucose availability involvement for the hypoxic HIF-1α and CA9 expression in GBM cells. Hypoxia significantly influences the behaviour of human tumour cells by activation of genes involved in the adaptation to hypoxic stress. The main objective in malignant GBM therapy is either to eradicate the tumour or to convert it into a controlled, quiescent chronic disease. Aza., SU.D2, Chetomin or CA9-siRNA possesses functional CA9 inhibitory characteristics when applied against human cancers with hypoxic regions like GBM. They may be used as alternative or in conjunction with other direct inhibitors possessing similar functionality, thereby rendering them as potential optimal tools for the development of an optimized therapy in human brain cancer treatment.     

The relation between resting heart rate and cancer incidence,cancer mortality and all-cause mortality in patients with manifest vascular disease

BackgroundPrevious studies suggest that elevated resting heart rate (RHR) is related to an increased risk of cancer mortality. The aim of this study was to evaluate the relation between RHR and cancer incidence and mortality in patients with vascular disease.MethodsPatients with manifest vascular disease (n = 6007) were prospectively followed-up for cancer incidence and mortality. At baseline, RHR was obtained from an electrocardiogram. The relation between RHR and cancer incidence, cancer mortality and total mortality was assessed using competing risks models.ResultsDuring a median follow-up of 6.0 years (interquartile range: 3.1–9.3) 491 patients (8%) were diagnosed with cancer and 907 (15%) patients died, 248 (27%) died from cancer. After adjustment for potential confounders, the hazard ratio (HR) for incident cancer per 10 beats/min increase in RHR was 1.00 (95% confidence interval [CI]: 0.93–1.07). There was a trend toward an increased risk of colorectal cancer in patients with higher RHR (HR 1.15, 95% CI 0.97–1.36). The risk of all-cause mortality was increased in patients in the highest quartile of RHR compared to the lowest quartile (HR 1.86, 95% CI 1.53–2.27), but no effect of RHR on cancer mortality was observed (HR 1.01, 95% CI 0.70–1.46).ConclusionsIn patients with manifest vascular disease, elevated RHR was related to a higher risk of premature all-cause mortality, but this was not due to increased cancer mortality. RHR was not related to risk of overall cancer incidence, although a relation between elevated RHR and incident colorectal cancer risk could not be ruled out.     

Cancer survival in patients with HIV/AIDS in the era of highly active antiretroviral therapy in Taiwan: A population-based cohort study

Objectives: HIV-related immunosuppression has been associated with the development of AIDS-defining malignancies. We examined the overall survival of HIV-infected patients who developed cancer. Design: A retrospective cohort study. Methods: Using the Taiwan Longitudinal Health Insurance Database, we compared patients diagnosed with HIV (n = 9918) between January 1, 2002, and December 31, 2007 with age-matched controls (n = 99,180). Each patient was followed until the end of 2009 (least 2 years after the initial HIV diagnosis) to evaluate the incidence of malignancies. Results: The risk of overall malignancies in the HIV-infected cohort was 1.88 times higher than the risk of a first malignancy in the age-matched non-HIV infected cohort (incidence rate ratio [IRR]) = 2.05, p < 0.0001). The diagnosis of a malignancy was negatively correlated with survival in the HIV-infected cohort (p < 0.0011), and HIV infection had a synergistic effect on the survival of patients with malignancies compared with the non-HIV infected cohort, all of who had been newly diagnosed with cancer (p < 0.0001). However, the difference in the risk of developing nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Taiwan, between the two cohorts was not significant (IRR = 0.22, 95% CI = 0.03–1.65). Conclusions: The risk of cancer in HIV-infected patients in Taiwan has increased significantly in the era of highly active antiretroviral therapy. A history of HIV significantly affected the survival of the patients in our study cohort after they developed cancer.Evidence level: 2B.     

Socioeconomic inequalities in incidence of lung and upper aero-digestive tract cancer by age, tumour subtype and sex: a population-based study in Scotland (2000-2007)

BackgroundLung and upper aero-digestive tract (UADT) cancer risk is associated with socioeconomic inequality (SEI) but the degree of socioeconomic burden by age, tumour subtype, and sex is not known.MethodsWe reviewed 216,305 cases excluding non melanoma skin cancer (All Cancer) comprising 37,274 lung; 8216 head and neck; and 6534 oesophageal cancers from 2000 to 2007 classified into anatomical or morphology subtypes. Deprivation was measured using the Scottish Index of Multiple Deprivation and SEI was measured using the Slope Index of Inequality and the Relative Index of Inequality (RII). Analyses were partitioned by 5-year age group and sex. RII was adapted to rank tumour type contribution to All Cancer SEI and to examine subtype by age and sex simultaneously. Rank was defined as proportion of All Cancer SEI.ResultsAll Cancer SEI was greater for males (RII = 0.366; female RII = 0.279); the combination of lung and UADT SEI contributed 91% and 81% respectively to All Cancer SEI. For both sexes lung and UADT subtypes showed significant SEI (P < 0.001) except oesophageal adenocarcinoma in males (P = 0.193); for females, SEI was borderline significant (P = 0.048). Although RII rank differed by sex, all lung and larynx subtypes contributed most to All Cancer SEI with RII rank for oral cavity, oesophagus-squamous cell, and oropharynx following. For males 40–44 years, SEI increased abruptly peaking at 55–59 years. For females, SEI gradually peaked 10 years later. In both sexes, the SEI peak preceded peak incidence.ConclusionSEI in lung and UADT cancers vary greatly by age, tumour subtype and sex; these variations are likely to largely reflect differences between the sexes in risk behaviours which vary by birth cohort and are socioeconomically patterned.     

The risk of cancer in the offspring and parental length of life

BackgroundWe investigated if cancer onset in offspring is related to having short-lived parents for different cancer types and to see if there was a difference in smoking- and non-smoking related cancers.MethodsOur study included 524,391 individuals born in Norway 1940–1950. All children were followed up for cancer from the age of 20 until they were between 59 and 69 years. Parental longevity was examined by grouping parental age of death into parents dying before 75 years of age and parents dying at 75 years of age or older.ResultsAn increased risk of 1.14 (95%CI = 1.10–1.19) among male offspring and 1.08 (95%CI = 1.04–1.12) among female offspring was observed for total cancer when both parents died before the age of 75 compared to offspring with two long-lived parents. The highest increase was found for cancer in the lungs and trachea for both male (HR = 1.67, 95%CI = 1.50–1.86) and female offspring (HR = 1.53, 95%CI = 1.33–1.76). For other smoking-related cancers, the risk was lower. No increased risk was observed for non-smoking-related cancers.ConclusionOffspring of long-lived parents have lower risk of developing cancer compared with offspring of short-lived parents. Intergenerational transmission of risk factors from parents to offspring may play an important role, especially for tobacco-related cancers. However, genetic factors cannot be ruled out, since consistent evidence has implicated genetic factors in smoking behaviour.     

TEP/TDM au FDG et hibernome : à propos d’un cas

Hibernoma is a rare benign tumour of soft tissue, generally asymptomatic, usually discovered in young adults. It is a form of lipoma that originates from brown adipose tissue. Its diagnosis is based on histology, the main differential diagnoses being lipoma and liposarcoma. Its appearance on FDG PET/CT has being described only in few case reports. We report here the case of a 68-year-old patient with ENT cancer in whom an adipose tumour in the left axilla has been discovered on CT performed for staging. The diagnosis of hibernoma was suggested in the report of FDG PET/CT examination and was consistent with results of other imaging modalities. On MRI, contrast enhancement was observed after gadolinium contrast injection, which was not typical for a lipoma. On PET/CT, the FDG uptake by the adipose tumour was very intense (SUVmax = 16), which is characteristic for hibernoma that derives from brown adipose tissue. Imaging was unable to distinguish between hibernoma and liposarcoma. The diagnosis of benign mixed hibernoma-lipoma was ascertained on histopathology after complete resection of the tumour. Elements favouring hibernoma over liposarcoma are present in this observation: high avidity for FDG (SUVmax > 10) and a fluctuating intensity of uptake, SUVmax of the tumour increasing from 16 to 48 within 16 months in the presented case. A high SUVmax on FDG PET in an adipose tumour on CT seems to be more suggestive of a benign tumour, hibernoma, than of its malignant counterpart, liposarcoma.     

Quantifying the changes in survival inequality for Indigenous people diagnosed with cancer in Queensland,Australia

The survival inequality faced by Indigenous Australians after a cancer diagnosis is well documented; what is less understood is whether this inequality has changed over time and what this means in terms of the impact a cancer diagnosis has on Indigenous people. Survival information for all patients identified as either Indigenous (n = 3168) or non-Indigenous (n = 211,615) and diagnosed in Queensland between 1997 and 2012 were obtained from the Queensland Cancer Registry, with mortality followed up to 31st December, 2013. Flexible parametric survival models were used to quantify changes in the cause-specific survival inequalities and the number of lives that might be saved if these inequalities were removed. Among Indigenous cancer patients, the 5-year cause-specific survival (adjusted by age, sex and broad cancer type) increased from 52.9% in 1997–2006 to 58.6% in 2007–2012, while it improved from 61.0% to 64.9% among non-Indigenous patients. This meant that the adjusted 5-year comparative survival ratio (Indigenous: non-Indigenous) increased from 0.87 [0.83–0.88] to 0.89 [0.87–0.93], with similar improvements in the 1-year comparative survival. Using a simulated cohort corresponding to the number and age-distribution of Indigenous people diagnosed with cancer in Queensland each year (n = 300), based on the 1997–2006 cohort mortality rates, 35 of the 170 deaths due to cancer (21%) expected within five years of diagnosis were due to the Indigenous: non-Indigenous survival inequality. This percentage was similar when applying 2007–2012 cohort mortality rates (19%; 27 out of 140 deaths). Indigenous people diagnosed with cancer still face a poorer survival outlook than their non-Indigenous counterparts, particularly in the first year after diagnosis. The improving survival outcomes among both Indigenous and non-Indigenous cancer patients, and the decreasing absolute impact of the Indigenous survival disadvantage, should provide increased motivation to continue and enhance current strategies to further reduce the impact of the survival inequalities faced by Indigenous people diagnosed with cancer.     

Cerebral vasodilator properties of Danshen and Gegen: A study of their combined efficacy and mechanisms of actions

Danshen and Gegen are two commonly used Chinese herbal medicines for treatment of cardiovascular diseases. The aim of the present study was to elucidate the combination effects of these two herbs on cerebral vascular tone and their underlying mechanisms of actions. Basilar artery rings were obtained from rats and precontracted with U46619. Cumulative administrations of aqueous extracts of Danshen, Gegen, or the two herbs combined (DG; ratio 7:3) produced concentration-dependent relaxation of the artery rings. Statistical analysis on these findings produced a combination index (CI) of 1.041 at ED₅₀, which indicates the two herbs produced additive vasodilator effects when used as a combined decoction. Removal of the endothelium had no effect on the vasodilator properties of Danshen, Gegen, and DG. However, their maximum effects (Imax) were significantly blunted by a K_ATP channel inhibitor glibenclamide, a non-selective K⁺ channel inhibitor tetraethylammonium (TEA), and by a combination of K⁺ channel inhibitors (glibenclamide + TEA + iberiotoxin + 4-aminopyridine + barium chloride). In addition, Danshen, Gegen, and DG produced augmentation of K_ATP currents and inhibited Ca²⁺ influx in vascular smooth muscle cells isolated from rat basilar arteries. Furthermore, these agents inhibited CaCl₂-induced contraction in the artery rings. In conclusion, the present study showed that Danshen and Gegen produced additive vasodilator effects on rat cerebral basilar arteries. These effects were independent of endothelium-derived relaxant factors (EDRF), but required the opening of K_ATP channels and inhibition of Ca²⁺ influx in the vascular smooth muscle cells. It is suspected that the cerebral vasodilator effects of Danshen and Gegen produced either on their own or in combination, can help patients with obstructive cerebrovascular diseases.