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.     

No association between educational level and pancreatic cancer incidence in the European Prospective Investigation into Cancer and Nutrition

Introduction: Until now, studies examining the relationship between socioeconomic status and pancreatic cancer incidence have been inconclusive. Aim: To prospectively investigate to what extent pancreatic cancer incidence varies according to educational level within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: In the EPIC study, socioeconomic status at baseline was measured using the highest level of education attained. Hazard ratios by educational level and a summary index, the relative indices of inequality (RII), were estimated using Cox regression models stratified by age, gender, and center and adjusted for known risk factors. In addition, we conducted separate analyses by age, gender and geographical region. Results: Within the source population of 407, 944 individuals at baseline, 490 first incident primary pancreatic adenocarcinoma cases were identified in 9 European countries. The crude difference in risk of pancreatic cancer according to level of education was small and not statistically significant (RII = 1.14, 95% CI 0.80–1.62). Adjustment for known risk factors reduced the inequality estimates to only a small extent. In addition, no statistically significant associations were observed for age groups (adjusted RII_{≤ 60 years} = 0.85, 95% CI 0.44–1.64, adjusted RII_{>60 years} = 1.18, 95% CI 0.73–1.90), gender (adjusted RII_male = 1.20, 95% CI 0.68–2.10, adjusted RII_female = 0.96, 95% CI 0.56–1.62) or geographical region (adjusted RII_{Northern Europe} = 1.14, 95% CI 0.81–1.61, adjusted RII_{Middle Europe} = 1.72, 95% CI 0.93–3.19, adjusted RII_{Southern Europe} = 0.75, 95% CI 0.32–1.80). Conclusion: Despite large educational inequalities in many risk factors within the EPIC study, we found no evidence for an association between educational level and the risk of developing pancreatic cancer in this European cohort.     

The association between UGT1A7 polymorphism and cancer risk: a meta-analysis

Background: studies investigating the associations between UDP-glucuronosyltransferase 1A7 (UGT1A7) gene polymorphisms and various carcinomas risk reported conflicting results. To derive a more precise estimation of the association, we have conducted a meta-analysis. Methods: data were collected from the following electronic databases: PubMed, Medline and Chinese Biomedical Literature Database, with the last report up to September 2011. Case–control studies containing available genotype frequencies of UGT1A7 were chose. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of association. Results: a total of 22 separate case–control studies including 3852 cases and 5604 controls based on the search criteria were involved in this meta-analysis. The combined results based on all studies showed that there was a statistically significant link between UGT1A7*3 allele and cancer risk (OR = 1.31, 95%CI = 1.14–1.50, P = 0.0001). In the stratified analysis by racial descent, significant increased risk was found in Asian population for UGT1A7*3 allele (OR = 1.41, 95%CI = 1.22–1.63, P < 0.00001). No significant associations were found between the UGT1A7 polymorphism and cancer susceptibility among Caucasians and African-Americans. In the subgroup analysis by cancer types, significant associations were found in UGT1A7*2 allele (OR = 1.23, 95%CI = 1.06–1.43, P = 0.006) and *3 allele (OR = 1.51, 95%CI = 1.11–2.06, P = 0.009) for hepatocellular carcinoma, *3 allele for lung cancer (OR = 1.36, 95%CI = 1.11–1.68, P = 0.004) and for bladder cancer (OR = 1.50, 95%CI = 1.09–2.07, P = 0.01). Conclusions: This meta-analysis suggests that the UGT1A7*3 allele is a risk factor for cancer among Asians, especially for hepatocellular carcinoma.     

Increase in breast cancer incidence among older women in Mumbai: 30-year trends and predictions to 2025

Background: Increasing trends in the incidence of breast cancer have been observed in India, including Mumbai. These have likely stemmed from an increasing adoption of lifestyle factors more akin to those commonly observed in westernized countries. Analyses of breast cancer trends and corresponding estimation of the future burden are necessary to better plan rationale cancer control programmes within the country. Methods: We used data from the population-based Mumbai Cancer Registry to study time trends in breast cancer incidence rates 1976–2005 and stratified them according to younger (25–49) and older age group (50–74). Age-period-cohort models were fitted and the net drift used as a measure of the estimated annual percentage change (EAPC). Age-period-cohort models and population projections were used to predict the age-adjusted rates and number of breast cancer cases circa 2025. Results: Breast cancer incidence increased significantly among older women over three decades (EAPC = 1.6%; 95% CI 1.1–2.0), while lesser but significant 1% increase in incidence among younger women was observed (EAPC = 1.0; 95% CI 0.2–1.8). Non-linear period and cohort effects were observed; a trends-based model predicted a close-to-doubling of incident cases by 2025 from 1300 mean cases per annum in 2001–2005 to over 2500 cases in 2021–2025. Conclusions: The incidence of breast cancer has increased in Mumbai during last two to three decades, with increases greater among older women. The number of breast cancer cases is predicted to double to over 2500 cases, the vast majority affecting older women.     

Genetic and environmental influences on oxidative damage assessed in elderly Danish twins

Previous studies have shown an association between oxidative stress and various diseases in humans including cancer, cardiovascular disease, diabetes, and chronic respiratory disease. To what extents this damage is determined by genetic and environmental factors is unknown. In a classical twin study with 198 elderly twins we examined the contributions of genetic versus environmental factors to nucleic acid oxidation and lipid peroxidation. Urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and dinor,dihydro F₂-isoprostane metabolites (F₂-IsoP-M) was measured using liquid chromatography–tandem mass spectrometry. The environmental influence on nucleic acid oxidation and lipid peroxidation was predominant, leaving only little influence from genetic factors, as evidenced by no differences in intraclass correlations between monozygotic (MZ) and dizygotic (DZ) twins, neither for 8-oxodG (r_MZ = 0.55, r_DZ = 0.47; P = 0.43), F₂-IsoP-M (r_MZ = 0.33, r_DZ = 0.22; P = 0.42), nor 8-oxoGuo (r_MZ = 0.45, r_DZ = 0.58; P = 0.21). Accordingly, heritability estimates for the three markers of oxidative damage were low (h² = 0.17–0.22). The three urinary markers of oxidative stress were closely correlated (r = 0.60–0.84). In conclusion, we demonstrated in a large population of elderly Danish twins that “whole-body” oxidative damage to nucleic acids and lipids is predominantly determined by potentially modifiable nongenetic factors.     

IκBα polymorphisms were associated with increased risk of gastric cancer in a southern Chinese population: a case-control study

AimNuclear factor-kappa B inhibitor alpha (IκBα) polymorphisms were found to be associated with inflammatory diseases. However, the association between IκBα polymorphisms with gastric cancer is still unknown. We aim to investigate the association between IκBα polymorphisms and gastric cancer risk in a large population-based case–control study among southern Chinese.Main methodsA population-based case–control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1010 gastric cancer patients and 1500 healthy controls were enrolled in this study. IκBα polymorphisms were identified by sequencing of IκBα gene ranging from the 2 kb promoter region to the 3.5 kb genomic region. Polymorphisms in IκBα were analyzed by TaqMan SNP genotyping assay.Key findingsrs17103265 deletion homozygote (?/?) had significantly increased gastric cancer risk (OR = 2.11, 95% CI = 1.17–3.83, P = 0.01), compared with rs17103265 T homozygote (TT). rs17103265 (?/?) genotype was significantly associated with increased risk of intestinal-type gastric cancer with (OR = 2.21, 95% CI = 1.19–4.08, P = 0.01), but not with the diffuse or mix type of gastric cancer. rs17103265 (?/?) was associated with poorly differentiated gastric cancer (OR = 2.05, 95% CI = 1.07–3.94, P = 0.03), but not with moderately or well differentiated gastric cancer. A significant decrease in luciferase activity was observed in rs17103265 deletion allele as compared with the vector containing the rs17103265 T allele (P < 0.0001). rs17103265 polymorphism was not associated with the prognosis of gastric cancer patients.SignificanceIκBα rs17103265 deletion homozygote is a novel genetic risk factor for gastric carcinogenesis, especially for the development of certain subtypes of gastric cancer in southern Chinese population.     

Survival trends of cancer amongst the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK

Introduction: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults. Methods: Subjects (n = 3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan–Meier estimation and Cox regression. Results: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR) = 1.75; 95% confidence interval (CI) = 1.11–2.76) and lymphoma (HR = 2.05; 95% CI = 1.09–3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR = 0.50; 95% CI = 0.28–0.89). This was independent of socioeconomic deprivation. Conclusion: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services.     

Recent decline in the U.S. death rate from myeloproliferative neoplasms, 1999-2006

Background: Myeloproliferative neoplasms (MPNs) are classified as neoplasms of uncertain or unknown behavior in the International Classification of Diseases (ICD) Version 10 and can contribute to risk of death from complications (especially thrombosis). Methods: U.S age-standardized death rates using ICD-Version 10 codes relevant to classical MPN (i.e., polycythemia vera, essential thrombocythemia, and “chronic myeloproliferative disease”) were examined for 1999–2006. The underlying cause of death and also all causes (“multiple causes” or “mentions”) coded on death certificates were considered. Trends were assessed by using percentage change (PC) in rate between 1999 and 2006, and annual percentage change (APC) estimated from linear regression. Results: The decline in death rates was large for MPN, whether based only the underlying cause (PC = ?19.7%, APC = ?3.4%) or on the substantially higher rates based on any cause (PC = ?24.1%, APC = ?3.8%), and was consistent by gender and age group (<65 and 65+ years). For deaths with MPN coded as other than the underlying cause, cardiovascular diseases were the most common underlying cause and the ASR for these deaths declined substantially (PC = ?40.0%). Conclusions: Use of the underlying cause of death in surveillance will considerably underestimate MPN-related mortality rates in the population. Studies are needed on treatment in random samples of MPN patients from population-based cancer registries. Continued surveillance of MPN-related mortality rates in the population is needed in view of recent attempts (including the use of aspirin) to control cardiovascular complications of MPN.     

The racial disparity in breast cancer mortality in the 25 largest cities in the United States

Introduction: Although the racial disparity in breast cancer mortality is widely discussed there are no studies that analyze this phenomenon at the city level. Methods: We used national death files, abstracting those cases for which the cause was malignant neoplasm of the breast (ICD-10 = C50) for the numerators and American Community Survey data for the denominators. The 25 largest cities in the US were the units of analysis. Non-Hispanic Black:non-Hispanic White rate ratios (RRs) were calculated, along with their confidence intervals, as measures of the racial disparity. Seven ecological (city-level) variables were examined as possible correlates. Results: Almost all the NHB rates were greater than almost all the NHW rates. All but 3 of the RRs (range 0.78–2.09; median = 1.44) were >1, 13 of them significantly so. None of the RRs < 1 were significant. From among the 7 potential correlates, only median household income (r = ?0.43, p = 0.037) and a measure of segregation (r = 0.42, r = 0.039) were significantly related to the RR. Conclusion: This is the first study that we have been able to locate which examines city-level racial disparities in breast cancer mortality. The results are of concern for several cities and for the field in general. A strategy for reducing this disparity in Chicago is in place and may serve as a model for other cities wanting to initiate a similar process. Clearly it is time to take action.     

Polymorphisms in MSH2 gene and risk of gastric cancer, and interactions with lifestyle factors in a Chinese population

Background: Although polymorphisms in DNA mismatch repair (MMR) gene MSH2 have been associated with risks of many cancers, little is known about their etiology role in gastric cancer (GC) and the potential interacting role with lifestyle factors known to damage DNA. Methods: A population-based study was conducted in 3 counties (Jintan, Taixing and Huaian) of Jiangsu Province, the high-risk areas of GC in China. We investigated the association of polymorphisms IVS12?6T>C and IVS10+12G>A in MSH2 gene with the risk of GC and the potential gene–lifestyle interaction. Results: The risk of GC was found to be associated with the IVS12?6C allele (CC vs TT, OR = 2.34, 95% CI: 1.17–4.71) and IVS10+12A allele (GA or AA vs GG, OR = 1.55, 95% CI: 1.14–2.21; and GA vs GG, OR = 1.51, 95% CI: 1.04–2.17). Stratified analysis indicated that an increased risk of GC also was observed in: suspected familial subjects carrying the IVS12?6T>C (OR = 1.68, 95% CI: 1.27–2.66) or IVS10+12G>A (OR = 2.57, 95% CI: 1.53–4.10); or younger subjects carrying the IVS12?6T>C (OR = 2.15, 95% CI: 1.24–3.91) or IVS10+12G>A (OR = 2.23, 95% CI: 1.20–4.33); or male subjects carrying the IVS10+12G>A (OR = 1.64; 95% CI: 1.10–2.54). Furthermore, the combined IVS12?6CC and IVS10+12AA genotypes also significantly increased the risk of GC (OR = 2.12, 95% CI: 1.22–3.66). Statistically significant interactions were observed between: IVS10+12G>A and drinking, high pickled food or fried food intake (OR = 2.32; 95% CI: 1.43–3.78, OR = 2.55; 95% CI: 1.48–4.21 and OR = 2.88; 95% CI: 1.70–4.94, respectively); and IVS12?6T>C and high pickled food intake or fried food intake (OR = 2.65; 95% CI: 1.62–4.47 and OR = 2.48; 95% CI: 1.42–4.13, respectively). Conclusion: The IVS10+12G>A and IVS12?6T>C polymorphisms in MSH2 gene appear to be associated with risk of GC in this Chinese population. Risk for GC, stratified by related genotypes, was further modified by drinking, high pickled food or fried food intake. Larger prospective studies are needed to confirm these findings.     

Interaction between GSTM1 genotype and IL-6 on mortality in older adults: results from the ilSIRENTE study

Background and aimsThe inflammatory process is related to oxidative stress and inflammation was proven to be a strong determinant of the aging process and to ultimately lead to death. The aim of the present study was to assess if, in a population of older adults, the effect of antioxidant genes GSTM1 and GSTT1 genotypes on mortality may differ depending on levels of inflammation.MethodsData are from 353 older persons aged ?80 years enrolled in the ilSIRENTE study. Study population was divided into two groups computed based on the median value of serum IL-6 (low IL-6, n = 177 and high IL-6, n = 176). All participants were followed up for 48 months.ResultsMean age of study participants was 85.8 years (Standard Deviation 4.8), 235 (66.6%) were women. Overall 48/177 participant (27.1%) in the low IL-6 group died during the study period, compared with 97/176 (55.1%) in the high IL-6 group (p < 0.001). After adjusting for potential confounders, GSTM1 wildtype had no effect on mortality in the low IL-6 group (RR = 1.07; 95% CI 0.46–2.47), but it was associated with a significant lower mortality rate in the high IL-6 level (RR = 0.33; 95% CI 0.15–0.69). Testing the interaction between IL-6 and GSTM1 genotype, we found a significant result (p = 0.02). No significant effect of GSTT1 genotype on mortality was shown in participants with low and high IL-6 level.ConclusionGSTM1 wildtype is associated with reduced mortality among older adults with high levels of inflammation, but not among those with low levels of inflammation.     

Genetic polymorphisms involved in the inflammatory response and lung cancer risk: A case-control study in Japan

Evidence is accumulating that chronic inflammation may have an important mechanism for the development and progression of lung cancer. Therefore, genetic polymorphisms in genes that involved in the inflammatory response may be associated with lung cancer risk. We evaluated the role of tumor necrosis factor α (TNFA) rs1799724, interleukin 1β (IL1B) rs16944, IL6 rs1800796, myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR = 1.64, 95% CI = 1.19–2.26) and IL6 rs1800796 (OR = 1.41, 95% CI = 1.02–1.96) were associated with lung cancer risk. In addition, we assessed interactions between the polymorphisms and smoking. The polymorphisms did not significantly modify the association between smoking and lung cancer. As TNFA triggers a cytokine cascade, the modifying effect of the TNFA rs1799724 genotypes on the association of any of the remaining polymorphisms with lung cancer risk was also examined. There was a significant interaction between TNFA rs1799724 and MPO rs2333227 (P_interaction = 0.058). Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the inflammation pathway in lung cancer.     

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.     

Trends in esophageal cancer mortality in China during 1987-2009: age, period and birth cohort analyzes

Background: Esophageal cancer is one of the most commonly diagnosed malignant tumors in China. The aim of this study was to provide the representative and comprehensive informations about the long-term mortality trends of this disease in China between 1987 and 2009, using joinpoint regression and generalized additive models (GAMs). Methods: Age-standardized mortality rates (ASMR), overall and truncated (35–64 years), were calculated using the direct calculation method, and joinpoint regression was performed to obtain the estimated annual percentage changes (EAPC). GAMs were fitted to study the effects of age, period and birth cohort on mortality trends. Results: ASMR exhibited an overall remarked decline for rural females (EAPC = ?2.3 95%CI: ?3.3, ?1.2), urban males (EAPC = ?1.8 95%CI: ?2.6, ?1.0) and urban females (EAPC = ?3.7 95%CI: ?4.9, ?2.4), but a small drop observed was not statistically significant for rural males (EAPC = ?0.9 95%CI: ?2.0, 0.3). The declines in ASMR were more noticeable for urban residents in recent years. Among all the residents, age effect showed an progressively increasing trend, whereas cohort effect declined steadily after the year corresponding to the maximum risk value. Period effect seemed to remain substantially unchanged throughout the years. Conclusions: Although variations in mortality rates were observed according to sex and area, the overall decreasing trends in esophageal cancer mortality were found in most Chinese people, aside from rural males. The findings could correspond to the changes in age- and cohort-related factors in the population. Further study is required to understand these potential factors.     

N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation

A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1 (R′ = H, CH₂Ph, COPh) substituent in conjunction with a C-3 –CHN–C₆H₄–4-X (X = F, Me, CF₃, Cl) substituent were synthesized and evaluated as inhibitors of cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases, compounds 15 (R¹ = CH₂Ph, X = F), 17 (R¹ = CH₂Ph, X = CF₃), 18 (R¹ = COPh, X = F) and 20 (R¹ = COPh, X = CF₃) were identified as effective and selective COX-2 inhibitors (COX-2 IC₅₀’s = 0.32–0.84 μM range; COX-2 selectivity index (SI) = 113 to >312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino)methyl]indole (20) emerged as the most potent (COX-1 IC₅₀ >100 μM; COX-2 IC₅₀ = 0.32 μM) and selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX-2 inhibitor in contrast to the reference drug indomethacin that is a potent and selective COX-1 inhibitor (COX-1 IC₅₀ = 0.13 μM; COX-2 IC₅₀ = 6.9 μM, COX-2 SI = 0.02). Molecular modeling studies employing compound 20 showed that the phenyl CF₃ substituent attached to the CN spacer is positioned near the secondary pocket of the COX-2 active site, the CN nitrogen atom is hydrogen bonded (N?NH = 2.85 Å) to the H90 residue, and the indole N-1 benzoyl is positioned in a hydrophobic pocket of the COX-2 active site near W387.     

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

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

CYP1AI, glutathione S-transferase gene polymorphisms and risk of Polycythemia vera

Background: Associations between polymorphisms for gene encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the present study was to evaluate the association of polymorphisms of cytochrome P450 (CYP1A1) and GST deletions with the incidence of Polycythemia vera (PV) among the Jordanian population. Methods: The study included 61 PV patients and 70 cancer-free healthy controls. CYP1A1 (m1, m2, m3, m4) and GST (T1, M1) genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. The risk of cancer associated with gene polymorphisms was estimated by calculations of odds ratio (ORs) and confidence intervals (95% CIs) using Mantel–Haenszel statistics. Results: A statistically significant difference between the PV group and the control group was observed in the case of GSTM1 null genotype with 3.38 fold increase in risk of developing PV (95% CI = 1.63–7.01, p = 0.001) while GSTT1 null genotype showed no significance (OR = 1.11; 95% CI = 0.50–2.44, p = 0.38). No significant association was found between the CYP1A1 mutant genotypes (m1, m2, m4) and PV. The m3 genotype was absent in both patients and controls. Interestingly, a substantial significant increase of PV risk for the combination of GSTM1 null genotype and CYP1A1 m1 (T6235C) genotype was observed (OR = 4.38; 95% CI = 1.15–16.73, p = .02). Furthermore, the present case–control study showed that the studied Jordanian population generally resembles Caucasian populations with respect to the frequencies of CYP1A1 polymorphisms. Conclusion: Our data suggests that GSTM1 null genotype alone and in combination with CYP1A1 m1 genotype may be predisposing risk factors for PV in the Jordanian population.     

Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response

Acute kidney injury (AKI) frequently afflicts patients undergoing cardiopulmonary bypass and independently predicts death. Both hemoglobinemia and myoglobinemia are independent predictors of postoperative AKI. Release of free hemeproteins into the circulation is known to cause oxidative injury to the kidneys. This study tested the hypothesis that postoperative AKI is associated with both enhanced intraoperative hemeprotein release and increased lipid peroxidation assessed by measuring F₂-isoprostanes and isofurans. In a case–control study nested within an ongoing randomized trial of perioperative statin treatment and AKI, we compared levels of F₂-isoprostanes and isofurans with plasma levels of free hemoglobin and myoglobin in 10 cardiac surgery AKI patients to those of 10 risk-matched controls. Peak plasma free hemoglobin concentrations were significantly higher in AKI subjects (289.0 ± 37.8 versus 104.4 ± 36.5 mg/dl, P = 0.01), whereas plasma myoglobin concentrations were similar between groups. The change in plasma F₂-isoprostane and isofuran levels (repeated-measures ANOVA, P = 0.02 and P = 0.001, respectively) as well as the change in urine isofuran levels (P = 0.04) was significantly greater in AKI subjects. In addition, change in peak plasma isofuran levels correlated not only with peak free plasma hemoglobin concentrations (r² = 0.39, P = 0.001) but also with peak change in serum creatinine (r² = 0.20, P = 0.01). Postoperative AKI is associated with both enhanced intraoperative hemeprotein release and enhanced lipid peroxidation. The correlations among hemoglobinemia, lipid peroxidation, and AKI indicate a potential role for hemeprotein-induced oxidative damage in the pathogenesis of postoperative AKI.     

Determination of whole body circadian phase in lung cancer patients: melatonin vs. cortisol

Background: A quantifiable and reliable technique for the determination of body circadian phase applicable to non-laboratory studies would allow the evaluation of circadian dysregulation. In this study we evaluated feasible methodologies to individualize whole body circadian phase in lung cancer patients. Methods: Cortisol and melatonin serum levels were measured in blood samples collected every 4 h for 24 h from eleven male controls and nine men suffering from non-small cell lung cancer. Circadian rhythmicity was evaluated and the 4-hourly fractional variations (FV) were calculated to evaluate the dynamics of the rise and fall in serum levels. Results: Overall cortisol serum levels were higher in cancer patients (p < 0.001), and lower for melatonin, but not significantly (p = 0.261). Original serum levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values at night for melatonin and near awakening for cortisol. Using all data after normalization to percent of individual mean, ANOVA detected a significant time-effect (p < 0.001) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) in each group. Overall fractional variation (FV) levels were lower for cortisol in cancer patients and higher for melatonin, but these differences were not significant. FV levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values prior to darkness onset for melatonin and near mid-dark for cortisol. ANOVA also detected a significant time-effect (p < 0.002) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) for FV in each group, with maximal FV preceding maximal serum levels by ～3 h for melatonin and ～5 h for cortisol. Conclusions: A chronobiological evaluation of serum levels and fractional variations for cortisol and especially melatonin is a valuable methodology to define body circadian phase in lung cancer patients. It is possible to describe the complex process of hormone secretion with a methodology that allows the definition of both temporal characteristics and dynamic components. Impact: This kind of analysis might be useful in the study of hormone secretion(s) in cancer patients and other diseases and to guide therapeutic interventions. While lung cancer patients may have a negative prognostic value based upon stage and/or other hormonal aspects of their hypothalamus–pituitary–thyroid–adrenal axis function, patients that nevertheless maintain circadian rhythmicity in key body rhythm markers may still be eligible candidates for a chronotherapeutic approach of treatment(s).