Cervical human papillomavirus and HIV infection in women of child-bearing age in Abidjan, Côte d'Ivoire, 2010.

BACKGROUND: We sought to document the association of Human immunodeficiency Virus (HIV) infection and immunodeficiency with oncogenic Human Papillomavirus (HPV) infection in women with no cervical neoplastic lesions identified through a cervical cancer screening programme in Côte d'Ivoire. METHODS: A consecutive sample of women stratified on their HIV status and attending the national blood donor clinic or the closest HIV clinic was recruited during a cervical cancer screening programme based on the visual inspection. Diagnosis of HPV infection and genotype identification were based on the Linear Array; HPV test. RESULTS: A total of 445 (254 HIV-positive and 191 HIV-negative) women were included. The prevalence of oncogenic HPV infection was 53.9% (95% confidence interval (CI) 47.9-59.9) in HIV-positive women and 33.7% (95% CI 27.1-40.3) in HIV-negative women (odds ratio (OR)=2.3 (95% CI 1.5-3.3)). In multivariate analysis, HIV-positive women with a CD4 count <200 cells mm(3) or between 200 and 499 cells mm(3) were more likely to harbour an oncogenic HPV compared with women with a CD4 count ≥500 cells mm(3) with OR of 2.8 (95% CI 1.1-8.1) and 1.7 (95% CI 1.0-2.9), respectively. CONCLUSION: A high prevalence of oncogenic HPV was found in women with no cervical neoplastic lesions, especially in HIV-positive women. Despite antiretroviral use, immunodeficiency was a main determinant of the presence of oncogenic HPV.

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer.

BACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients.

Alternative forms of tobacco use.

BACKGROUND: A review of the available scientific literature concerning forms of tobacco use other than regular cigarettes, cigars and pipes, the nature of such products, prevalence data and trends, health effects, regulatory issues and preventive measures. RESULTS: Narghile (water pipe), bidis, kreteks and other forms of oral tobacco are traditionally used in many low-income countries, and some of these are currently spreading to the Western countries. They are all linked to negative effects similar to, and often greater than, those associated with common cigarette smoking. Various potentially reduced exposure products (PREPs), including snus, targeted at smokers aware of the health risks of regular cigarettes, have recently been developed by the tobacco industry. Their pathogenic potential varies widely and is not fully known; it is in any case greater than that of pure nicotine forms (such as medicinal nicotine). Their use as cigarette substitutes should not be considered even by inveterate smokers who are unable or unwilling to quit nicotine before further independent evaluation and control. CONCLUSIONS: There is no such thing as a safe tobacco product. Like cigarettes, alternative forms of tobacco use need regulatory measures that are adapted to local situations and supplemented by preventive measures within the World Health Organization's Framework Convention for Tobacco Control.

Flexible regression models for dynamic prediction of survival in elderly in presence of cancer or other chronic diseases.

We consider degradation and failure time models with multiple failure modes adapted for the statistical analysis of survival in the elderly in presence of chronic diseases such as cancer, but also other conditions like dementia, Alzheimer, diabetes, etc... These models can be applied in gerontology, general medicine, biology and demography for the analysis of longevity and survival of highly complex biological systems as any human is.

The growing incidence of cancer: role of lifestyle and screening detection (Review).

The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population, as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed: i) over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased; ii) obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other lifestyle-related factors; iii) there is evidence that the environment has changed over the same time scale as the recent rise in cancer incidence, and that this change included the accumulation of many new carcinogenic factors in the environment; iv) genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through gene-environment interactions; v) age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children; vi) the fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical window period may explain why current epidemiological studies may be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment contributes to the rising trend in cancer incidence.

A lack of neuroblastoma in Down syndrome: a study from 11 European countries.

An epidemiological investigation in 11 European countries comprising a total childhood population of 54.1 million children and using 8 separate data sources was conducted to evaluate the occurrence of neuroblastoma in Down syndrome (DS). No cases of DS were detected among 6724 infants and children with neuroblastoma, although more than five were expected. This highly significant result (P = 0.0045 according to the Poisson test) is consistent with data in the literature, which contains only two poorly detailed cases in epidemiological studies and one ganglioneuroma in a DS mosaic patient. Like other tumors, such as leukemias, testicular germ cell tumors and lymphomas are in excess in DS patients; the lack of neuroblastomas does not reflect a general decreased incidence of cancer but rather a specific underrepresentation of this precise tumor. S-100 b protein, the gene for which maps to the long arm of chromosome 21, (a) is overproduced in DS patients, (b) produces growth inhibition and differentiation of neural cells in vitro, (c) is abundant in good-prognosis neuroblastomas, and (d) has been shown to induce growth inhibition and differentiation and cell death in several human and murine neuroblastoma cell lines and could be responsible for this variation. Additional epidemiological and experimental studies are warranted to confirm our interpretation of these data.

[Smoking (active or passive) in relation to fertility, medically assisted procreation and pregnancy]. / Tabagisme (actif ou passif) en relation avec la fertilité, la procréation médicalement assistée et la grossesse.

Maternal and paternal smoking are associated with numerous problems of reproduction and pregnancy. Among men, active smoking reduces the quality and mobility of the spermatozoa which could result in loss of fertility. It also increases the risk of impotence. Moreover, active smoking of the father is responsible for passive smoking for the mother and her baby. Among women, active smoking has a negative impact on fertility and in case of treatments against infertility, the chances of success are reduced. It leads to delayed conception and increases the risk of ectopic pregnancies and placental complications. It reduces the risk of pre-eclampsia but it also worsens its consequences. Passive smoking has not been associated with certainty with any clear impact on fertility among men and women. By contrast, active and passive smoking can lead to intra-uterine growth retardation and a lower birth weight.

The role of physical exercise in the occurrence of Parkinson's disease.

A case-control study of Parkinson's disease and physical exercise was conducted in a cohort of 50,002 men who attended Harvard College (Cambridge, Mass) or the University of Pennsylvania (Philadelphia) between 1916 and 1950 and were followed up in adulthood for morbidity and mortality data. Cases of Parkinson's disease were identified from responses to mailed questionnaires and death certificates through 1978. Four controls from the same population were selected for each case. The association between physical activity at the time of college and subsequent risk of Parkinson's disease was evaluated for 137 cases and 548 controls, whereas the data on physical activity in adulthood before the disease occurrence was available only for 94 of these cases. Having belonged to a varsity team or having done regular physical exercise in college was associated with a lower nonsignificant risk of Parkinson's disease. In adulthood, practice of moderate or heavy sports was linked to a reduced risk, although more precise analysis revealed that there was only a modest nonsignificant reduction in risk for subjects who do a moderate amount of physical exercise, but this negative association disappears at higher levels of physical expenditure. These results, which require further confirmation, are compatible with a slight protective effect of physical exercise on the risk of Parkinson's disease, although the lack of association cannot be refuted.

Why can't we convince the young not to smoke?

Tobacco is the largest cause of preventable death and morbidity in the world. Significant progress has been made in national tobacco control programmes, followed by a significant reduction in smoking-associated diseases. However, other populations have taken up the habit and the worldwide surge in cigarette smoking by young people is particularly worrisome. Based on our own experience as well as reported data, we examined determinants of tobacco use, at the familial, peer and societal levels as well as various prevention strategies based on legislation, health promotion and society awareness. Reasons for failures include under-enforcement of legislation, uniform approach to diverse populations and too limited means. Recommendations for future actions should include integrated policies and health programmes. Most importantly, the society outlook on tobacco should be changed, making non-smoking the norm and the objective.

Trends in tobacco smoking among adolescents in Lyon, France.

To provide information that may promote more effective cancer prevention, we identified factors associated with regular smoking among adolescents in Lyon, France. School grades where these factors began to influence regular smoking were also identified. Seven consecutive cross-sectional anonymous surveys were conducted in three public schools, beginning in grade 6ème (average age 11.5 years) in 1993 and ending in grade Terminale (average age 17.4 years) in 1999. All classes in each respective grade were surveyed, with 3650 completed questionnaires for all years combined. Prevalence of current regular smoking is presented according to school grade for 17 variables identified as significantly related to regular smoking in a multivariate logistic regression analysis. Important factors associated with regular smoking were identified as early as grade 6ème and included not viewing the taking care of one's health as important, not eating breakfast regularly, associating with groups where smoking occurs, having a best friend who smokes, and having a brother and/or sister who smokes. Not regularly reading was first associated with an increased risk of regular smoking in grade 5ème. Not living with both parents, alcohol drinking, episodes of drunkenness, illicit drug use, and sexual relationships were positively associated with regular smoking in the middle and later grades, when these questions were first asked. Not playing sports and not playing with computers were initially associated with an increased risk of regular smoking in grade 3ème.

A systematic survey of breast cancer incidence in the Département of Rhône, France.

A systematic survey of all centres of diagnosis and care of breast cancer patients in the Rhône "département" of France was carried out to evaluate, for the year 1985, the incidence rate of breast cancer in an urban, industrialised part of France not covered by a cancer registry. Two hundred and fifty seven institutions or individuals were involved, covering the public and private sectors in the Rhône département, but also in neighbouring cities and elsewhere in France, which also enabled a search to be carried out for cases diagnosed or treated outside the département. Altogether, over this 1-year period, 801 new cases were identified (791 women and 10 men). This study demonstrated a high incidence of female breast cancer (80.5 new cases per 100,000 woman-years, standardised to the world population) which was particularly marked among women aged 40-60. This incidence is higher than that described by the cancer registry of the neighbouring département of Isère, but is close to the incidence found in Geneva. Results also concur with the relatively high mortality rate from breast cancer observed in the Rhône département.

Breast cancer prognostic significance of some modified urinary nucleosides.

The prognostic significance of six urinary modified nucleosides, 5-methylcytidine (5-MeCyd), 4-acetylcytidine (4-AcCyd), 1-methylinosine (1-MeIno), 1-methyladenosine (1-MeAdo), 7-methylguanosine (7-MeGua) and pseudouridine (psi-Urd) was evaluated in 68 breast cancer patients of the specialized cancer hospital of Lyon (France). Excretions of 1-MeIno and 1-MeAdo were significantly higher in patients hospitalized in the medical rather than surgical ward, reflecting more advanced disease, and also among patients who died within 5 years of follow-up as compared to those still alive. These results suggest an unfavourable prognostic significance of high urinary excretion of 1-MeIno and 1-MeAdo in breast cancer patients.

Rethinking breast cancer risk and the environment: the case for the precautionary principle.

The World Health Organization recently reported that breast cancer has become the most common cancer in women throughout the world. Known risk factors account for less than half of all cases of breast cancer, and inherited germ line mutations occur in at most only 10% of all cases. Cumulative exposure to estradiol and other hormones links many of the established risk factors for breast cancer. This paper reviews epidemiologic and toxicologic evidence on breast cancer risks and presents a comprehensive construct of risk factors intended to focus on the identification of those factors that can be controlled or modified. We attempt to provide a framework for interpreting the etiologic interplay of endogenous metabolic changes and environmental changes in the etiology of breast cancer. The construct we develop distinguishes between those risk factors that are directly causal, such as ionizing radiation and inherited germ cell defects, those vulnerability factors that extend the time period during which the breast undergoes development, and those contributing factors that increase total hormonal stimulation of the breast. Some hormonally active compounds, such as those in soy and broccoli and other phytoestrogen-containing foods, can be protective against breast cancer, while others, such as some environmental contaminants, appear to increase the risk of the disease by increasing levels of harmful hormones. Efforts to explain patterns of breast cancer should distinguish between these different risk factors. Identification of vulnerability and contributing risk factors can foster the development of public policy to reduce the burden of this prevalent cancer. Prudent precautionary principles suggest that reducing exposure to avoidable or modifiable risk factors should receive high priority from the public and private sectors.

Epidemiology of breast cancer: an environmental disease?

Breast cancer is the leading cancer site in women, both in the developed and the developing world. Incidence rates are increasing in many countries, although, in some, mortality may be stable or slightly decreasing. Geographical differences exist, with high rates of disease in North America, North Europe and Oceania, intermediate rates in South and Central America as well as South and East Europe, and low rates in Africa and Asia. Most of the literature reports that genetic inherited factors account for less than 5% of cases, although some authors advance higher figures, up to about 10%. Risk factors for breast cancer are related to the reproductive life of women: early menarche, nulliparity or late age at first birth, late menopause, diet and physical exercise, as well as hormonal factors, be they endogenous (high levels of free or not bound to SHBG estrogens) or exogenous (long-term use of oral contraceptives or menopausal hormone replacement). The present review does not aim to be exhaustive and fully comprehensive, or to present in detail domains currently well known and accepted by all. On the contrary, it modestly wishes to highlight potentially controversial conditions which could in the future be recognized as new risk factors.

Tobacco smoking and cancer: a brief review of recent epidemiological evidence.

This report summarises the epidemiological evidence on the association between tobacco smoking and cancer, which was reviewed by an international group of scientists convened by IARC. Studies published since the 1986 IARC Monograph on "Tobacco smoking" provide sufficient evidence to establish a causal association between cigarette smoking and cancer of the nasal cavities and paranasal sinuses, nasopharynx, stomach, liver, kidney (renal cell carcinoma) and uterine cervix, and for adenocarcinoma of the oesophagus and myeloid leukaemia. These sites add to the previously established list of cancers causally associated with cigarette smoking, namely cancer of the lung, oral cavity, pharynx, larynx, oesophagus, pancreas, urinary bladder and renal pelvis. Other forms of tobacco smoking, such as cigars, pipes and bidis, also increase risk for cancer, including cancer of the lung and parts of the upper aerodigestive tract. A meta-analysis of over 50 studies on involuntary smoking among never smokers showed a consistent and statistically significant association between exposure to environmental tobacco smoke and lung cancer risk. Smoking is currently responsible for a third of all cancer deaths in many Western countries. It has been estimated that every other smoker will be killed by tobacco.

Prognostic factors for mortality in nasopharyngeal cancer: accounting for time-dependence of relative risks.

BACKGROUND: Few studies have assessed the role of prognostic factors for mortality from nasopharyngeal cancer and even fewer used multivariable methods. Most of these studies relied on the Cox model without testing the proportional hazards assumption. METHODS: A cohort of 76 cases of nasopharyngeal cancer recorded in the Rhône, France, between 1980 and 1985, was followed until 1995. Proportional hazards assumption was tested for each putative prognostic factor. Two multivariable models were built using forward selection of prognostic factors: the Cox model and a flexible model in which variables not meeting the proportional hazards assumption were represented by a time-varying hazard ratio. RESULTS: Only Epstein Barr Virus Nuclear Antigen (EBNA) serology, a marker of infection by the Epstein-Barr virus, and tumoral extent were selected in the analysis based on the Cox model. In contrast, four prognostic factors were significant at alpha = 0.05 level in the flexible model: initial EBNA serology, tumoral histology, age and tumoral extent, the last two not verifying the proportional hazards assumption. The relative risk of age increases with duration of follow-up whereas the effect of tumoral extent changes in a non-monotonic pattern. CONCLUSION: We showed the importance of taking into account the non-proportionality of hazards which can influence results and yield new insights about the role of prognostic factors in nasopharyngeal cancer. Because of the small size of our cohort, our results have to be confirmed in an independent study.

Tobacco and cancer: how to react to the evidence.

Tobacco is a remarkable product when considering the number of diseases to which it can reliably be linked as a causal agent or at least as a factor which is partially responsible for the occurrence of disease. If we only look at cancer, tobacco is responsible for the vast majority of cancers of the lung, trachea and bronchus; a proportion of cancers of the bladder and of the renal pelvis; a considerable proportion of cancers of the oral cavity, lip, pharynx, larynx and oesophagus with, for these sites, a large potentiation of risk when associated with the drinking of alcohol; a proportion of cancers of the pancreas and possibly of renal adenocarcinoma. In addition, among women, tobacco use has been linked with an increased risk of cervical cancer. In order to evaluate the present burden of tobacco-related cancers in the world precisely, one needs to be able to consult precise statistics of cancer occurrence, tobacco use and the relationship between the two. The availability of such data varies greatly across countries. Although mortality, and to a lesser extent, morbidity cancer statistics are collected in many parts of the world, the coverage is far from exhaustive and of uniform quality. Commercial or governmental sources of data on tobacco also exist, but the most important missing link is knowledge of the population-specific risk attributable to tobacco use in various countries for all tobacco-related diseases. Despite imperfect knowledge, the link between tobacco use and cancer is clear enough to demand strong action.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of tobacco and alcohol-related cancers in western Europe.

The relative importance of the tobacco and alcohol-related cancer burden varies across countries. Within western Europe, the incidence of lung cancer has a clearly different geographical pattern to the incidence of alcohol-related cancer. Each country's public health policies should take into account its own tobacco and alcohol-related morbidities.

Survival after proton-beam irradiation of uveal melanomas.

PURPOSE: To evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DESIGN: Interventional case series. METHODS: In this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: The 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P =.045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. CONCLUSION: Our results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

An infant with Down syndrome and retinoblastoma. A possible non-fortuitous association.

AIM: To evaluate the association between Down syndrome and retinoblastoma. METHOD: Presentation of a case report and review of the literature. RESULTS: A retinoblastoma was observed in a 10-month-old boy with Down syndrome. A review of the literature yielded 14 other cases, suggesting a possible excess of retinoblastoma in Down syndrome, as previously proposed by two epidemiological studies. The possible roles of external physical agents and hyperplastic and dysplastic lesions of the retina in subjects with Down syndrome is discussed. CONCLUSION: A positive association between Down syndrome and retinoblastoma is possible. An epidemiological study on this subject is needed to better ascertain this potential link.