Cu,Zn-Superoxide Dismutase Gene Dosage and Cell Resistance to Oxidative Stress: A Review

It is well established that superoxide dismutase (SOD) is the irresplaceable enzyme for aerobic lifestyle. Our understanding of its role has made strides recently as the result of gene transfection approach. Available data on consequences of Cu,Zn-SOD gene transfection in cell resistance to oxygen toxicity are reviewed. There are data that increasing only Cu,Zn-SOD can be toxic, and the balance between Cu,Zn-SOD and peroxide-removing enzymes is supposed to be of prime importance in the antioxidant defence. Role of Cu,Zn-SOD deregulation in carcinogenesis is discussed.     

The influence of vitamin D deficiency on cancers and autoimmune diseases development

There is a growing number of diseases which prevalence can be associated with vitamin D deficiency. The link between low cholecalciferol concentration and bone diseases is well established, however there is also data suggesting that it may influence development and progression of different cancers and autoimmune diseases. The in vitro studies proved that the active vitamin D metabolite--1,25(OH)(2)D(3) may arrest the cell cycle progression, induce apoptosis as well as regulate T cells and antigen presenting cells function. Results of the in vivo experiments suggest that vitamin D deficiency accelerates development of autoimmune diseases and cancers in animals. Epidemiological studies imply that the vitamin D deficiency is also associated with the increased incidence of autoimmune diseases and cancers in people. The main determinant of vitamin D serum concentration in a human body is skin synthesis. The changes in the lifestyle, air pollution as well as a common use of sun screens caused that the contemporary European receives little sunlight compared to his ancestors. According to the recent epidemiological studies, the vitamin D concentrations in serum of people who live in high latitudes (above 34 degrees N/S), including Poland, is far from being sufficient. This paper reviews results of the recent studies concerning the potential role of the vitamin D in the development of cancers and autoimmune diseases, as well as provides guidelines for vitamin D supplementation.     

Phage-plasmid interactions in bacteria]

A review is devoted to consideration of the basic types of interaction of moderate and virulent bacteriophages and extrachromosomal elements in bacterial cells. Various experimental data confirm diversity of such interactions as well as resistance of bacteria to productive phage infection. Role of plasmids in such processes as abortion infection, lysogenic state, reparation of phage DNA as well as the effect of plasmids on the basic stages of phage development in the cells are analyzed. Possible mechanisms for limiting development of phages as a result of plasmids' presence in bacterial cells are considered.     

The relationship between factors affecting endogenous oestradiol levels in postmenopausal women and breast cancer

Breast cancer accounts for 1 in 4 of all female cancers worldwide; approaching 13,000 women dying per year in the UK alone. Seventy five per cent of all diagnosed breast cancers are oestrogen receptor (ER) positive. Ovarian synthesis of oestrogens ceases at menopause and as breast cancer is more prevalent in postmenopausal women the non-ovarian sources of oestrogen are important in disease progression. There is now considerable evidence that associates increased breast cancer risk with prolonged exposure to oestrogens hence greater attention is now being given to determining whether the measurement of plasma oestrogen may assist in identifying chemoprevention target groups. Studies suggest that in most postmenopausal patients the intra-tumoural concentrations of oestrogens are up to 20-fold higher than those present in the plasma however, while the extent of biosynthesis of oestrogens within breast tissue is a major determinant of local exposure, plasma levels are a useful indicator of overall metabolism in peripheral tissues. As such it is important to understand factors that influence these measurements. This review summarises the impact of lifestyle such as body mass index, together with the role of genetic polymorphisms placed within the context of designing future epidemiological studies and breast cancer risk algorithms.     

Non-Steroidal Anti-Inflammatory Drugs Use Is Associated with Reduced Risk of Inflammation-Associated Cancers: NIH-AARP Study

Background

Chronic inflammation has been linked to cancers, and use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence.

Methods

We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996–1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases.

Findings

During 2,715,994 person-years of follow-up (median 10.1 person-years), there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR) (95% CI)) 0.90 (0.87–0.93), 0.80 (0.74–0.85), 0.82 (0.78–0.87), 0.88 (0.84–0.92), and 0.88 (0.85–0.92) respectively)].

Conclusions

After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.     

Cancer incidence among Danish Seventh-day Adventists and Baptists

IntroductionAmerican Seventh-day Adventists have been reported to have lower cancer mortality and incidence than the general population. Adventists do not consume tobacco, alcohol or pork, and many adhere to a lacto-ovo-vegetarian lifestyle. Baptists discourage excessive use of alcohol and tobacco. In this study, we investigated whether the incidence of cancer in a large cohort of Danish Adventists and Baptists was different compared to the general Danish population.Material and methodsWe followed 11,580 Danish Adventists and Baptists in the nationwide Danish Cancer Registry, which contains information on cases of cancer for 1943–2008. Cancer incidence in the cohort was compared with that in the general Danish population as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), and within-cohort comparisons were made with a Cox model.ResultsLower cancer incidences were observed for both Seventh-day Adventist men (SIR, 66; 95% CI, 60–72) and women (85; 80–91). The same result was observed for Baptists although not as low. The differences were most pronounced for smoking-related cancers such as those of the buccal cavity and lung (SIR, 20; 13–30 for Seventh-day Adventist men and 33; 22–49 for Seventh-day Adventist women). The incidences of other lifestyle-related cancers, such as of stomach, rectum, liver and cervix, were also decreased. In general, the SIRs were lower for men than for women, and Adventists had lower hazard rates than Baptists.DiscussionOur findings point to the benefits of compliance with public health recommendations and indicate that lifestyle changes in the population might change the cancer risks of individuals.     

Cancer in Guam and Hawaii: A comparison of two U.S. Island populations

BackgroundCancer disparities within and across populations provide insight into the influence of lifestyle, environment, and genetic factors on cancer risk.MethodsGuam cancer incidence and mortality were compared to that of Hawaii using data from their respective population-based, central cancer registries.ResultsIn 2009–2013, overall cancer incidence was substantially lower in Guam than in Hawaii for both sexes while overall cancer mortality was higher for Guam males. Cervical cancer incidence and prostate cancer mortality were higher in Guam. Both incidence and mortality were higher among Guam men for cancers of the lung & bronchus, liver & intrahepatic bile duct, and nasopharynx; Chamorro men were disproportionately affected by these cancers. Filipinos and Whites in Guam had lower overall cancer incidence compared to Filipinos and Whites in Hawaii. Although breast cancer incidence was significantly lower in Guam compared to Hawaii, women in Guam presented at younger ages and with rarer disease histologies such as inflammatory carcinoma were more prevalent. Guam patients were also diagnosed at younger ages for cancers of bladder, pancreas, colon & rectum, liver & intrahepatic bile duct, lung & bronchus, stomach, non-Hodgkin lymphoma, and leukemia.ConclusionSmoking, infectious agents, and betel nut chewing appear to be important contributors to the burden of cancer in Guam. Earlier onset of cancer in Guam suggests earlier age of exposure to key risk factors and/or a more aggressive pathogenesis. Contrasting cancer patterns within Guam and between Guam and Hawaii underscore the potential influence of genes, lifestyle, and environmental factors on cancer development and progression.     

Nutrition, insulin, insulin-like growth factors and cancer.

The incidence of colon, pancreatic, and kidney cancers, as well as aggressive prostate cancer in men, and breast and endometrial cancer in women is invariably high in Western countries. Nutritional and related factors have been typically implicated. This review presents a model integrating nutrition, insulin and IGF-1 physiology ("bioactive" IGF-1), and carcinogenesis based on the following: (1) insulin and the IGF-1 axis function in an integrated fashion to promote cell growth and survival; (2) chronic exposure to these growth properties enhances carcinogenesis; (3) factors that influence bioactive IGF-1 will affect cancer risk. The model presented here summarizes the data that chronic exposure to high levels of insulin and IGF-1 may mediate many of the risk factors for some cancers that are high in Western populations. This hypothesis may help explain some of the epidemiologic patterns observed for these cancers, both from a cross-national perspective and within populations. Of particular importance is that some of relevant factors are modifiable through nutritional and lifestyle interventions. Out of a variety of perspectives presented, nutritional manipulation through the insulin pathway may be more feasible than attempting to influence total IGF-1 concentrations, which are determined largely by growth hormone. Further study is required to test these conclusions.     

The important role of stratum corneum lipids for the cutaneous barrier function

The skin protects the body from unwanted influences from the environment as well as excessive water loss. The barrier function of the skin is located in the stratum corneum (SC). The SC consists of corneocytes embedded in a lipid matrix. This lipid matrix is crucial for the lipid skin barrier function. This paper provides an overview of the reported SC lipid composition and organization mainly focusing on healthy and diseased human skin. In addition, an overview is provided on the data describing the relation between lipid modulations and the impaired skin barrier function. Finally, the use of in vitro lipid models for a better understanding of the relation between the lipid composition, lipid organization and skin lipid barrier is discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.     

Trends in cancer mortality rates among migrants in Australia: 1981-2007

Background: Previous studies have shown that migrants have lower cancer mortality rates compared to the Australian-born population, particularly for colorectal and breast cancers, which are associated with an affluent lifestyle. This study seeks to update knowledge in this field by examining mortality from colorectal, stomach, lung, melanoma, breast and bladder cancers, as well as all cancers combined between 1981 and 2007. Methods: Data were obtained from the Australian Bureau of Statistics. Average annual age and sex-standardised mortality rates were calculated for each region of birth, period of death registration and cancer site. Results: Generally, mortality rates declined over the study period for most conditions for the majority of migrant groups. Notable exceptions included migrants from South Eastern Europe and Eastern Europe who experienced a significant increase in mortality due to all cancers combined and Australian-born individuals who recorded a significant increase in mortality due to melanoma of the skin. Migrants generally had more favourable cancer mortality outcomes, particularly for colorectal cancer and melanoma. Migrants from Southern Europe, South Eastern Europe, Chinese Asia and Southern Asia had the greatest advantage. However, migrants displayed higher rates of stomach, lung and bladder cancers than the Australian-born population. Conclusion: The migrant advantage can in part be explained by the protective effects of diet, lifestyle and reproductive behaviours. Possible explanations for why some migrants display greater mortality from stomach and bladder cancer include the consumption of abrasive, salted and preserved foods and higher rates of smoking. Greater emphasis should be placed on targeting at-risk migrant groups through screening and education programs at migrant resource centres and community groups. The study calls for further research to explain the observed trends, which has the potential to uncover important risk and protective factors.     

Informal education and health promoting approaches in adult cancer survivors

This review looks at the available data relating to the informal education aspects and other health promoting approaches applied by adult cancer survivors to reduce the risk of cancer. The implications of such behavioral interventions on oncology practice are discussed. We also highlight areas of future research to pursue. Available data show that many cancer survivors remain engaged in risky health behaviors post-diagnosis, which are associated with an increased risk of disease's recurrence. However, over the last years patients seem to increasingly receive adequate risk-based medical care. The application of appropriate informal education approaches, such as diet, exercise, and cessation of former unhealthy habits, such as smoking and alcohol has facilitated behavioral changes in cancer survivors, thoroughly improving their well being and overall quality of life (QOL). Most of the research studies published to date have applied structured lifestyle interventions on intensive, individualized counseling sessions delivered by trained personnel or psychosocial-based mediations and reported that these approaches are largely effective in promoting the adoption of a healthier lifestyle in cancer survivors. These interventions have been reported to reduce the risk of cancer recurrence and thus to obtain an obvious positive impact on their well-being and overall QOL. However, there is still insufficient evidence to conclude and support with confidence the effectiveness of any of these behavioral interventions and therefore future interventions should be initiated to assess the long-term effects and validating outcomes of lifestyle and other psychosocial interventions.     

RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease

RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto''s thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39–22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto''s thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer.     

Health and the city: physical health and mental health

In France, city size has very little bearing on the mortality rate as a function of age and life expectancy and it is in large cities that these indicators are the most favorable. No increase in maternal or infant mortality rates or deaths due to cancers has been observed in large cities. The lower mortality rate linked to respiratory and cardiovascular diseases in large urban areas contradicts the fears concerning the impact of air pollution. Deaths linked to lifestyle are less frequent in big cities, which could be due to social structures (socio-professional level: the proportion of white-collar workers and professionals is higher in bigger cities than in the suburbs or small cities). However, although the overall mortality rate is lower, it should be emphasized that there is in large cities a greater incidence of sexually transmitted diseases, AIDS and certain infectious diseases (because of social diversity and the fact that certain individuals seeking anonymity and marginality are drawn to large cities). In terms of mental health, the breakdown of family structures, instability, unemployment, the lack of parental authority and failing schools render adolescents vulnerable and hinder their social integration. When the proportion of adolescents at risk is high in a neighborhood, individual problems are amplified and social problems result. In order to restore mental and social health to these neighborhoods, ambitious strategies are necessary which take into account family and social factors as well as environmental ones. At the present time, when physical health is constantly improving, the most pressing problems are those related to lifestyle and mental health which depend for a large part on social factors.     

Spinal Orexin-2 Receptors are Involved in Modulation of the Lateral Hypothalamic Stimulation-Induced Analgesia

Neurochemical Research - Role of the orexinergic system in pain modulation is well studied and involvement of the spinal orexin-1 receptors is well documented. In this study, we examined role of...     

Associations of plasma high-sensitivity C-reactive protein concentrations with all-cause and cause-specific mortality among middle-aged and elderly individuals

Background

The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is a strong predictor of disease development and premature mortality in the general population. Unhealthy lifestyle habits such as smoking or unhealthy eating is known to elevate the suPAR level. We aimed to investigate whether change in lifestyle habits impact on the suPAR level, and whether the resultant levels are associated with mortality.

Results

Paired suPAR measurements from baseline- and the 5-year visit of the population-based Inter99 study were compared with the habits of diet, smoking, alcohol consumption, and physical activity. Paired suPAR measurements for 3225 individuals were analyzed by linear regression, adjusted for demographics and lifestyle habits. Compared to individuals with a healthy lifestyle, an unhealthy diet, low physical activity, and daily smoking were associated with a 5.9, 12.8, and 17.6% higher 5-year suPAR, respectively. During 6.1 years of follow-up after the 5-year visit, 1.6% of those with a low suPAR (mean 2.93 ng/ml) died compared with 3.8% of individuals with a high suPAR (mean 4.73 ng/ml), P <  0.001. In Cox regression analysis, adjusted for demographics and lifestyle, the hazard ratio for mortality per 5-year suPAR doubling was 2.03 (95% CI: 1.22–3.37).

Conclusion

Lifestyle has a considerable impact on suPAR levels; the combination of unhealthy habits was associated with 44% higher 5-year suPAR values and the 5-year suPAR was a strong predictor of mortality. We propose suPAR as a candidate biomarker for lifestyle changes as well as the subsequent risk of mortality.

     

A method for the assessment of disease associations with single-nucleotide polymorphism haplotypes and environmental variables in case-control studies

The rough draft of the human genome map has been used to identify most of the functional genes in the human genome, as well as to identify nucleotide variations, known as "single-nucleotide polymorphisms" (SNPs), in these genes. By use of advanced biotechnologies, researchers are beginning to genotype thousands of SNPs from biological samples. Among the many possible applications, one of them is the study of SNP associations with complex human diseases, such as cancers or coronary heart diseases, by using a case-control study design. Through the gathering of environmental risk factors and other lifestyle factors, such a study can be effectively used to investigate interactions between genes and environmental factors in their associations with disease phenotype. Earlier, we developed a method to statistically construct individuals' haplotypes and to estimate the distribution of haplotypes of multiple SNPs in a defined population, by use of estimating-equation techniques. Extending this idea, we describe here an analytic method for assessing the association between the constructed haplotypes along with environmental factors and the disease phenotype. This method is also robust to the model assumptions and is scalable to a large number of SNPs. Asymptotic properties of estimations in the method are proved theoretically and are tested for finite sample sizes by use of simulations. To demonstrate the use of the method, we applied it to assess the possible association between apolipoprotein CIII (six coding SNPs) and restenosis by using a case-control data set. Our analysis revealed two haplotypes that may reduce the risk of restenosis.     

Comparison of Apolipoprotein (apoB/apoA-I) and Lipoprotein (Total Cholesterol/HDL) Ratio Determinants. Focus on Obesity, Diet and Alcohol Intake

The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I) has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women) as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia.     

Microanatomical diversity of the humerus and lifestyle in lissamphibians

A study of body size and the compactness profile parameters of the humerus of 37 species of lissamphibians demonstrates a relationship between lifestyle (aquatic, amphibious or terrestrial) and bone microstructure. Multiple linear regressions and variance partitioning with Phylogenetic eigenVector Regressions reveal an ecological and a phylogenetic signal in some body size and compactness profile parameters. Linear discriminant analyses segregate the various lifestyles (aquatic vs. amphibious or terrestrial) with a success rate of up to 89.2%. The models built from data on the humerus discriminate aquatic taxa relatively well from the other taxa. However, like previous models built from data on the radius of amniotes or on the femur of lissamphibians, the new models do not discriminate amphibious taxa from terrestrial taxa on the basis of body size or compactness profile data. To make our inference method accessible, spreadsheets (see supplementary material on the website), which allow anyone to infer a lissamphibian lifestyle solely from body size and bone compactness parameters, were produced. No such easy implementation of habitat inference models is found in earlier papers on this topic.     

The future excess fraction of cancer due to lifestyle factors in Australia

BackgroundMany cancers are caused by exposure to lifestyle, environmental, and occupational factors. Earlier studies have estimated the number of cancers occurring in a single year which are attributable to past exposures to these factors. However, there is now increasing appreciation that estimates of the future burden of cancer may be more useful for policy and prevention. We aimed to calculate the future number of cancers expected to arise as a result of exposure to 23 modifiable risk factors.MethodsWe used the future excess fraction (FEF) method to estimate the lifetime burden of cancer (2016–2098) among Australian adults who were exposed to modifiable lifestyle, environmental, and occupational risk factors in 2016. Calculations were conducted for 26 cancer sites and 78 cancer-risk factor pairings.ResultsThe cohort of 18.8 million adult Australians in 2016 will develop an estimated 7.6 million cancers during their lifetime, of which 1.8 million (24%) will be attributable to exposure to modifiable risk factors. Cancer sites with the highest number of future attributable cancers were colon and rectum (n = 717,700), lung (n = 380,400), and liver (n = 103,200). The highest number of future cancers will be attributable to exposure to tobacco smoke (n = 583,500), followed by overweight/obesity (n = 333,100) and alcohol consumption (n = 249,700).ConclusionA significant proportion of future cancers will result from recent levels of exposure to modifiable risk factors. Our results provide direct, pertinent information to help determine where preventive measures could best be targeted.