Lung cancer and exposure to tobacco smoke in the household

BACKGROUND. The relation between passive smoking and lung cancer is of great public health importance. Some previous studies have suggested that exposure to environmental tobacco smoke in the household can cause lung cancer, but others have found no effect. Smoking by the spouse has been the most commonly used measure of this exposure. METHODS. In order to determine whether lung cancer is associated with exposure to tobacco smoke within the household, we conducted a population-based case--control study of 191 patients with histologically confirmed primary lung cancer who had never smoked and an equal number of persons without lung cancer who had never smoked. Lifetime residential histories including information on exposure to environmental tobacco smoke were compiled and analyzed. Exposure was measured in terms of "smoker-years," determined by multiplying the number of years in each residence by the number of smokers in the household. RESULTS. Household exposure to 25 or more smoker-years during childhood and adolescence doubled the risk of lung cancer (odds ratio, 2.07; 95 percent confidence interval, 1.16 to 3.68). Approximately 15 percent of the control subjects who had never smoked reported this level of exposure. Household exposure of less than 25 smoker-years during childhood and adolescence did not increase the risk of lung cancer. Exposure to a spouse's smoking, which constituted less than one third of total household exposure on average, was not associated with an increase in risk. CONCLUSIONS. The possibility of recall bias and other methodologic problems may influence the results of case-control studies of environmental tobacco smoke. Nonetheless, our findings regarding exposure during early life suggest that approximately 17 percent of lung cancers among nonsmokers can be attributed to high levels of exposure to cigarette smoke during childhood and adolescence.     

Risk factors and life processes associated with the onset of suicidal behaviour during adolescence and early adulthood

BACKGROUND: This study examined associations between childhood circumstances, adolescent mental health and life events, and the development of suicidal behaviour in young people aged between 15 and 21 years. METHOD: Data were gathered over the course of a 21-year longitudinal study of a birth cohort of 1265 children born in New Zealand. The measures collected included: (1) patterns of suicidal behaviour (ideation, attempt) (15-21 years); (2) social background, family functioning, parental and individual adjustment during childhood (0-16 years); and (3) time dynamics of mental health and stressful life events during adolescence and early adulthood (15-21 years). RESULTS: By the age of 21 years, 28.8% of the sample reported having thought about killing themselves and 7.5% reported having made a suicide attempt. The childhood profile of those at greatest risk of suicidal behaviour was that of a young person reared in a family environment characterized by socio-economic adversity, marital disruption, poor parent-child attachment and exposure to sexual abuse, and who as a young adolescent showed high rates of neuroticism and novelty seeking. With the exception of the socio-economic and personality measures, the effects of childhood factors were largely mediated by mental health problems and exposure to stressful life events during adolescence and early adulthood. Mental health problems including depression, anxiety disorders, substance use disorder, and to some extent conduct disorder, in addition to exposure to adverse life events, were significantly associated with the onset of suicidal behaviours. CONCLUSIONS: Findings support a life course model of the aetiology of suicidal behaviour in which risk of developing suicidal behaviour depends on accumulative exposure to a series of social, family, personality and mental health factors.     

Testosterone-mediated immune functions and male life histories.

Recent advances in human life history theory have provided new insights into the potential selection pressures that were instrumental in the evolution of human and non-human primate males. However, gaps remain in our understanding of how primate males regulate and allocate energetic resources between survivorship and reproductive effort. Defense against parasitic infection is an important force shaping life history evolution. Proper performance of immunological responses against infection is influenced by many physiological systems, including metabolic, reproductive, and stress hormones. Because androgens influence and modulate immune, reproductive, and somatic metabolic functions, assessing changes in testosterone and immune factors during infection may yield insight into male physiological ecology. In this review, we examine male life history trade-offs between immune and reproductive endocrine functions as well as provide a comprehensive review of testosterone-immunocompetence relationships. Emphasis is placed on testosterone because it is a primary hormone shown to be crucial to energy-allocation processes in vertebrates. Non-primate species have been used more extensively in this research than humans or non-human primates, and therefore this extensive literature is organized and reviewed in order to better understand potential parallel relationships in primates, especially humans. Furthermore, we attempt to reconcile the many inconsistent results obtained from field studies on immune-endocrine interactions as well as detail various methodologies that may be used to forward this research in evolutionary anthropology.     

The effects of steroid hormone exposure on direct gene regulation

Steroid hormones have been widely overlooked as controllers of gene expression. Through the mechanisms of gene expression (DNA methylation, histone methylation, and RNAi), we discuss the impact of normal reproductive templates on the pulsatility and amplitude of potential gene-regulating treatment protocols. By examining the interactions of estradiol (E2) and progesterone (P4) in women, we propose that changes in physiologic reproductive hormone templates of exposure and timing can affect fertility and even cancer through the silencing or amplification of gene products; such as P53 and Bcl-2 in women. We suggest that uncontrolled hormone levels, due to aging and/or the environment, may be restored to a normal youthful template of gene expression through the fluctuating exogenous application of E2 and P4 that mimic the normal hormonal milieu of reproductive health. Furthermore, we hypothesize that restoration of normal hormone levels may lead to a lower risk of the chronic illnesses of aging and a better quality of life in patients suffering those conditions.     

Influence of early life exposures on incidence and remission of asthma throughout life

BACKGROUND: Knowledge of the effects of early environmental and congenital factors on the natural history of asthma may provide important clues to the pathogenesis of asthma. OBJECTIVE: We assessed associations between potential, early determinants and the incidence and remission of asthma throughout life, and tested whether the strength and direction of these associations varied in childhood, adolescence, and adulthood. METHODS: The data pertaining to the individual asthma history of 18,156 subjects, age 0 to 44 years, who attended the clinical stage of the European Community Respiratory Health Survey were analyzed retrospectively by life-event methods. Onset of asthma was defined as age at the first attack, and asthmatic patients were considered to be in remission if they had not been under treatment or had an attack of asthma in the past 24 months. Onset and remission were evaluated in 3 time windows: <10, 10 to 20, and > or =20 years of age. The associations of asthma with early determinants were estimated by hazard ratios (HRs). RESULTS: A family history of asthma or allergy was associated with a higher risk of developing asthma (HR, 1.89; 95% CI, 1.67-2.13) and a lower chance of remission (HR, 0.79; 95% CI, 0.64-0.99) throughout life. No matter what one's genetic predisposition was, early, acute respiratory infections were associated with an increased lifelong risk of asthma onset (pooled HR, 3.19; 95% CI, 2.75-3.69), whereas early contact with older children, which is a marker of prolonged, intermittent exposure to infectious agents, conferred permanent protection against asthma (HR, 0.84; 95% CI, 0.74-0.96) and increased the chance of remission in childhood asthma (HR, 1.50; 95% CI, 1.10-2.04). Pet ownership had a protective effect only in childhood (HR, 0.78; 95% CI, 0.74-0.96), whereas maternal smoking did not show a significant association with asthma. Female sex was negatively associated with the onset of asthma in childhood (HR, 0.62; 95% CI, 0.52-0.75) and positively in adulthood (HR, 2.01; 95% CI, 1.61-2.51). The pattern of associations was similar in sensitized (positive assay to specific IgE) and nonsensitized asthmatic patients. CONCLUSION: Genetic predisposition and exposure to infectious agents are major early determinants that influence a subsequent history of asthma. The length and type of exposure to infectious agents seem able either to promote or to suppress an anti-inflammatory process, unrelated to IgE, which can partially interfere with an acquired predisposition for asthma.     

Reproductive hormones, cancers, and conditions in relation to a common genetic variant of luteinizing hormone

A variant of the beta-subunit of luteinizing hormone (v-LH) is more common among populations also at higher risk for breast and ovarian cancer. To explore the possible relationship between these cancers and v-LH, we examined its frequency in premenopausal women, including 100 with a family history of ovarian cancer, 94 with carcinoma- in-situ of the breast, and 153 age and residence-matched controls. Reproductive histories were assessed and v-LH status measured by immunological assays from plasma drawn during the early follicular phase of cycles. For the entire study population, 283 (81.5%) were wild type; 61 (17.6%) were heterozygous; and three (0.9%) were homozygous for v-LH. Carrier frequency was not elevated among women with a family history of ovarian cancer or personal history of carcinoma-in-situ of the breast compared with controls. Women with the v-LH variant were less likely to report menstrual weight gain or ovarian cysts, more likely to report infertility, and have higher early follicular phase LH concentrations compared with women who were wild type. While there is no evidence from this study that v-LH increases risk for ovarian or breast cancer, we conclude that possession of v-LH may impact on some aspects of reproductive history and LH concentrations.     

早期子宫内膜癌诊疗研究

多数子宫内膜癌早期可有症状,根据发病的危险因素、临床症状、体征、辅助检查及术中的相关手段进行评估,及早发现并治疗,预后良好。低危患者实施淋巴结的切除,对其预后可能无影响,还可能增加术中及术后并发症。而子宫内膜癌淋巴结转移的特征为跳跃性转移,术前诊断存在局限性,手术病理分期仍是评估其转移状态的最佳方法,并为其预后及辅助治疗提供了一定的帮助。本文就子宫内膜癌的诊断及淋巴结切除指征、手术、预后及保留生育功能的治疗作一综述。     

Signals 1, 2 and B cell fate or: Where,when and for how long?

The role of the microbiota in multiple autoimmune diseases, including juvenile idiopathic arthritis (JIA) has earned substantial attention in the last 10 years. Increasing evidence suggests that the microbiota's link to JIA begins in early childhood, as early life events that influence the nature of the microbiota also appear to influence disease risk. In this review, we discuss these early life events including mode of delivery, infant feeding practice, antibiotics exposure, and other events and their impacts on the microbiota and on disease risk; reported abnormalities of the microbiota in children with JIA; mechanisms by which an altered microbiota at birth and later on in childhood may influence disease risk; and the prospects for therapeutic alteration of the microbiota in children with JIA.     

Epidemiologic perspective on immune-surveillance in cancer

Common 'themes' in epidemiology related to cancer risk beg a comprehensive mechanistic explanation. As people age, risk for cancer increases. Obesity and smoking increase the risk for many types of cancer. History of febrile childhood diseases lowers the risk for melanomas, leukemias, non-Hodgkin's lymphoma (NHL), and ovarian cancer. Increasing number of ovulatory cycles uninterrupted by pregnancies correlate positively with breast, endometrial, and ovarian cancer risk while pregnancies and breastfeeding lower the risk for these cancers as well as cancers of the colon, lung, pancreas, and NHL. Chronic inflammatory events such as endometriosis or mucosal exposure to talc increase the risk for several types of cancer. Mechanisms so far considered are site specific and do not explain multiple associations. We propose that most of these events affect cancer immunosurveillance by changing the balance between an effective immune response and immune tolerance of an emerging cancer. We review recently published data that suggest that immune mechanisms underlie most of these observed epidemiologic associations with cancer risk.     

Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers

The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose–response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless.Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure.     

A mechanistic look at the effects of adversity early in life on cardiovascular disease risk during adulthood

Early origins of adult disease may be defined as adversity or challenges during early life that alter physiological responses and prime the organism to chronic disease in adult life. Adverse childhood experiences or early life stress (ELS) may be considered a silent independent risk factor capable of predicting future cardiovascular disease risk. Maternal separation (MatSep) provides a suitable model to elucidate the underlying molecular mechanisms by which ELS increases the risk to develop cardiovascular disease in adulthood. The aim of this review is to describe the links between behavioural stress early in life and chronic cardiovascular disease risk in adulthood. We will discuss the following: (i) adult cardiovascular outcomes in humans subjected to ELS, (ii) MatSep as an animal model of ELS as well as the limitations and advantages of this model in rodents and (iii) possible ELS‐induced mechanisms that predispose individuals to greater cardiovascular risk. Overall, exposure to a behavioural stressor early in life sensitizes the response to a second stressor later in life, thus unmasking an exaggerated cardiovascular dysfunction that may influence quality of life and life expectancy in adulthood.     

Mouse allergen exposure, wheeze and atopy in the first seven years of life

Background: Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood. Objective: To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life. Methods: Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months. Results: Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis. Conclusions: Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life.     

Hormone replacement therapy in women treated for gynaecological malignancy.

Can we prescribe hormone replacement therapy (HRT) safely for women, with postmenopausal complaints who were treated for a gynaecological malignancy? Only three retrospective studies have investigated this issue in endometrial cancer patients. No recurrences or deaths occurred in these treated groups. However, the physician introduced bias through the selection of favourable groups. At present, combined estrogen and progestogen therapy is probably not contra-indicated in endometrial cancer stage I and probably also not in stage II, although so far there is only circumstantial evidence. Squamous cell cancers of the cervix, vulva, and vagina are unlikely to be influenced by HRT. In the only study available of women with ovarian cancer, < or = 50 years, estrogen replacement therapy did not have a negative influence on (disease-free) survival. According to the data currently available, no evidence exists that HRT adversely influences survival and overall survival after treatment for ovarian cancer. In general, adenocarcinomas of the cervix and leiomyosarcomas of the uterus may be managed such as the adenocarcinomas of the uterus. During the last 25 years, HRT has been shown to substantially reduce the risk of cardiovascular diseases, osteoporotic fractures and colon carcinoma. On the other hand there is a significant increase of the risk in breast cancer with prolonged use of > 5 years. Re-evaluation of the current view that HRT should no be given to women treated for a gynaecological malignancy is strongly warranted after evaluating the advantages and the disadvantages of HRT use in each individual patient. Long-term HRT in women treated for a gynaecological cancer must be based on the medical history of the individual patient (and her family).     

A life course approach to reproductive health: Theory and methods

Taking a life course approach to the study of reproductive health involves the investigation of factors across life and, also across generations, that influence the timing of menarche, fertility, pregnancy outcomes, gynaecological disorders, and age at menopause. It also recognises the important influence of reproductive health on chronic disease risk in later life. Published literature supports the use of an integrated life course approach to study reproductive health, which examines the whole life course, considers the continuity of reproductive health and the interrelationship between the different markers of this. This is in contrast to more traditional approaches that tend to focus only on contemporary risk factors and which consider each marker of reproductive health separately. For instance, we found evidence linking early life factors such as growth, socioeconomic conditions, and parental divorce with ages at menarche and menopause, although the nature of the relationship differs. We discuss the different theoretical models that are used within life course epidemiology and which postulate pathways linking exposures across the life course to health outcomes, using examples of relevance to the study of reproductive health. These highlight the importance of examining timing of exposures, such as during critical periods in early life, and the temporal order of exposures. How life course frameworks of reproductive health can be developed to help identify hypotheses to be tested is also demonstrated. This approach has implications for the development of effective health policy that moves beyond identifying not only the type of intervention but also the most appropriate time across life to intervene.     

Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life

Higher sibling exposure is associated with a reduced risk of asthma and other T helper 2 (Th2)-type disorders, possibly through a beneficial effect of higher infection load. The effect on Th1 disorders such as multiple sclerosis (MS) is less clear. Here we examine the association between asthma and MS, taking into account early life sibling exposure. A population-based case-control study in Tasmania, Australia based on 136 cases of magnetic resonance imaging (MRI)-confirmed MS and 272 community controls, matched on sex and year of birth. Study measures include cumulative exposure to total, older or younger siblings by age 6 years, history of doctor-diagnosed asthma and serological IgG responses to herpes viruses. MS cases were more likely (P = 0.02) than controls to have asthma which began before age of onset of MS symptoms compared to the corresponding age for controls. The absence of younger sibling exposure by age 6 years potentiated (P = 0.04) the association between asthma and MS. Compared to those with younger sibling exposure and no asthma, the adjusted odds ratio for MS for those with asthma and no younger sibling exposure was 7.22 (95% CI: 2.52, 20.65). Early life sibling exposure was associated with altered IgG serological responses to Epstein-Barr virus (EBV) and herpes simplex virus 1 (HSV1) in adulthood. Reduced early life sibling exposure appeared to contribute to the excess of asthma among MS cases by the time of MS onset. MS development may reflect factors that relate to a general immuno-inflammatory up-regulation of immune activity as well as disease specific factors. The link between early life sibling exposure and the immune response to herpes group viral antigens is consistent with a protective role for early life infections.     

Early life events and their consequences for later disease: a life history and evolutionary perspective.

Biomedical science has little considered the relevance of life history theory and evolutionary and ecological developmental biology to clinical medicine. However, the observations that early life influences can alter later disease risk--the "developmental origins of health and disease" (DOHaD) paradigm--have led to a recognition that these perspectives can inform our understanding of human biology. We propose that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course. Such adaptive processes allow genotypic variation to be preserved through transient environmental changes. Cues for plasticity operate particularly during early development; they may affect a single organ or system, but generally they induce integrated adjustments in the mature phenotype, a process underpinned by epigenetic mechanisms and influenced by prediction of the mature environment. In mammals, an adverse intrauterine environment results in an integrated suite of responses, suggesting the involvement of a few key regulatory genes, that resets the developmental trajectory in expectation of poor postnatal conditions. Mismatch between the anticipated and the actual mature environment exposes the organism to risk of adverse consequences-the greater the mismatch, the greater the risk. For humans, prediction is inaccurate for many individuals because of changes in the postnatal environment toward energy-dense nutrition and low energy expenditure, contributing to the epidemic of chronic noncommunicable disease. This view of human disease from the perspectives of life history biology and evolutionary theory offers new approaches to prevention, diagnosis and intervention.     

Systematic review of gamma-aminobutyric-acid inhibitory deficits across the reproductive life cycle

Deficiencies in the inhibitory functioning of gamma-aminobutyric acid (GABA) have been implicated in the pathophysiology of depressive disorders. Reproductive life cycle events, including menstruation, pregnancy, and menopause, are consistently associated with increased psychopathology, in particular mood disorders. Given that GABA-inhibitory activity may be modulated directly or indirectly by estrogen, progesterone, and their metabolites receptors, it has been hypothesized that GABA deficits may be evident during these reproductive periods. We aimed to compare GABA function among women during these “high-risk” reproductive periods to GABA function among women at other time periods. We conducted a systematic review of studies comparing women during reproductive life stages associated with depressive disorder risk (luteal phase of the menstrual cycle, perinatal period, and menopausal transition) to women at other time periods. The study outcome was GABA function. The review included 11 studies, 9 focused on the menstrual cycle, and 2 focused on the perinatal period. GABA-inhibitory function fluctuated across the menstrual cycle, with differing patterns in women with and without depressive disorders. GABA-inhibitory function was reduced in pregnancy and early postpartum compared to the nonpregnant state. Key limitations were the absence of studies evaluating the menopausal transition, and the heterogeneity of GABA outcome measures. GABA-inhibitory function fluctuates across the menstrual cycle and is reduced perinatally. This has potential implications for a role of GABAergically mediated interventions in the prevention and treatment of menstrual cycle-related and perinatal depressive disorders.     

A possible link between the pubertal growth of girls and ovarian cancer in their daughters

At puberty, the distance between the iliac crests of the female pelvis, measured by the intercristal and interspinous diameters, increases rapidly. This is mainly controlled by estrogens. We have followed up 6,370 women who were born in Helsinki during 1934–1944, and whose mothers' pelvic bones were measured during routine antenatal care. We have previously reported that women whose mothers had larger intercristal diameters had higher rates of breast cancer. We postulated that large intercristal diameters are markers of high circulating concentrations of estrogen, which are established at puberty, persist through reproductive life and cause genetic instability in differentiating breast cells in female embryos. We now report on ovarian cancer in the same cohort. Our hypothesis was that the risk of this cancer would also be higher in women whose mothers had broader hips. We found that, when compared with all other women, the hazard ratio for ovarian cancer was 3.3 (95% CI 1.6–7.0, P = 0.004) in the daughters of mothers whose interspinous diameter was greater than 27 cm. Among mothers who had an early menarche, each measure of broad hips was associated with increased risk of ovarian cancer in their daughters. We postulate that ovarian cancer is initiated by exposure of the fetal ovary to maternal sex hormones. Concentrations of these hormones may be higher in mothers who had an early menarche. The maternal sex hormone profile that initiates ovarian cancer may be the product of poor nutrition and growth in early childhood followed by catch‐up pre‐pubertal growth. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Gynecologic cancer screening and communication with health care providers in women with Lynch syndrome

We evaluated knowledge of gynecologic cancer screening recommendations, screening behaviors, and communication with providers among women with Lynch syndrome (LS). Women aged ≥25 years who were at risk for LS‐associated cancers completed a semi‐structured interview and a questionnaire. Of 74 participants (mean age 40 years), 61% knew the appropriate age to begin screening, 75–80% correctly identified the recommended screening frequency, and 84% reported no previous screening endometrial biopsy. Women initiated discussions with their providers about their LS cancer risks, but many used nonspecific terms or relied on family history. Most were not offered high‐risk screening options. While many women were aware of risk‐appropriate LS screening guidelines, adherence was suboptimal. Improving communication between women and their providers regarding LS‐related gynecologic cancer risk and screening options may help improve adherence.