Marilys Corbex

Polymorphism of the stress protein HSP70-2 gene is associated with the susceptibility to the nasopharyngeal carcinoma

Several studies have shown statistical evidence of association between nasopharyngeal carcinoma (NPC) and specific human leukocyte antigen (HLA) alleles and highlighted the presence of candidate genes for this cancer within or nearby the HLA. Given their chromosomal location within HLA and their determining role in the immune response to tumor cells, we designed a case-controlled study to investigate the potential association of the genetic variation of the tumor necrosis factor-alpha (TNF-alpha) and that of the heat shock protein 70-2 (HSP70-2) with NPC. We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNF-alpha promoter region and that of the HSP70-2 gene in 140 Tunisian patients with primary NPC and 274 healthy control subjects. No association was found between genetic variations in TNF-alpha and the risk of NPC in Tunisians. In contrast, a significant relative risk of NPC was found associated with the HSP70-2 homozygous genotype (P2/P2) (OR=2.309; P=0.006). The P2/P2 genotype of the HSP70-2 gene may be a marker of increased risk of NPC in Tunisians.

Features of breast cancer in developing countries, examples from North-Africa.

Epidemiological features of breast cancer appear to be different in developing countries compared to Western countries, with notably large proportions of young patients, male patients and aggressive forms of the disease. Using North-Africa (Morocco, Algeria, Tunisia, Libya and Egypt) as an example, we document the magnitude and explore possible explanations for such patterns. Articles and reports published since the seventies were reviewed. Results show that breast cancer incidence in females is 2-4 times lower in North-Africa than in Western countries while incidence in males is similar. Consequently, the relative proportion of male breast cancer is high (≈2% of all breast cancers). Similarly, the incidence of aggressive forms of the disease, like inflammatory or triple negative breast cancer (in females), is not higher in North Africa than in Western countries, but their relative proportion in case series (up to 10% for inflammatory and 15-25% for triple negative) is significantly higher because of low incidence of other forms of the disease. In North Africa, the incidence among women aged 15-49 is lower than in Western countries, but the very low incidence among women aged more than 50, combined to the young age pyramid of North-Africa, makes the relative proportions of young patients substantially higher (50-60% versus 20% in France). Such epidemiological features result mainly from peculiar risk factor profiles, which are typical for many developing countries and include notably rapid changes in reproductive behaviours. These features have important implications for breast cancer control and treatment.

Second primary cancers in patients with nasopharyngeal carcinoma: a pooled analysis of 13 cancer registries

ObjectiveTo study the risk of second primary cancers in nasopharyngeal carcinoma (NPC) patients and the risk of NPC as second primary cancer.MethodsWe used data from the cancer registries from Singapore and from 12 low-incidence areas, including a total of 8,947 first occurring NPC cases, and 167 second occurring cases. We calculated standardized incidence ratios (SIRs) by comparing the second cancer incidence in NPC patients to the first primary cancer incidence in non-cancer population. We also calculated SIRs of second NPC after other primaries.ResultsIn Singapore, the risk of cancers of the lung (SIR = 0.42), stomach (SIR = 0.41), and colon (SIR = 0.23) was significantly decreased after NPC, whereas that of cancer of the tongue (SIR = 11.1) was significantly increased. In Australia, Canada, and Europe, the risk of non-Hodgkin’s lymphoma (NHL) (SIR = 3.06), tongue cancer (SIR = 5.29), brain cancer (SIR = 3.89), myeloid leukemia (SIR = 3.85), and non-melanoma skin cancer (NMSC) (SIR = 3.47) was significantly increased after NPC. Incidences of second occurring NPCs following various primary cancers were not significantly altered compared to the incidence of first occurring NPCs.ConclusionsImmune suppression (NHL, NMSC), shared genetic factors (lung cancer, NHL, myeloid leukemia), and shared environmental risk factors (tongue and brain cancers) might explain the associations. Except for NHL, there was no evidence of association with other Epstein-Barr virus-related cancers.

XRCC1 and hOGG1 genes and risk of nasopharyngeal carcinoma in North African countries

Although genetic susceptibility to nasopharyngeal carcinoma (NPC) has been recognized for a long time, little is known about the responsible genes. X‐Ray repair cross‐complementing protein 1 (XRCC1) and human 8‐oxo‐guanine glycosylase 1 (hOGG1) genes are involved in deoxyribonucleic acid (DNA) repair and were found associated with NPC risk in three Asian case–control studies. The objective of the present study was to test these genes in a sample from North Africa, one of the major NPC endemic regions in the world. Three single nucleotide polymorphisms (SNPs) in the XRCC1 gene and one SNP in the hOGG1 gene were genotyped in 598 NPC cases from Morocco, Algeria, and Tunisia and 545 controls frequency matched by recruitment center, age, sex, and urban/rural household. The genotype and allelic distributions for the hOGG1 326Ser/Cys SNP and for the XRCC1 399Arg/Trp, 280Arg/His, and 194Arg/Trp SNPs did not differ significantly among NPC cases and controls. The XRCC1 194Trp allele frequency was significantly lower in the North African population than in Asian population (f = 0.04 vs. 0.31 in Cantonese Chinese and 0.21 Han Chinese). The hOGG1 326Ser allele frequency was significantly higher in the North African population (f = 0.73) than in Asian populations (f = 0.39 in Taiwanese). The results of the present study obtained from a large sample indicate that the XRCC1 and hOGG1 genes are unlikely to play a role in the susceptibility to NPC in North Africans. Our results do not corroborate those found in Asian population on smaller samples. Mol. Carcinog.

Cancer incidence in Morocco: report from Casablanca registry 2005-2007

Introduction Few population-based cancer registries are in place in developing countries. In order to know the burden of cancer in Moroccan population, cancer registry initiative was put in place in the Casablanca district, the biggest city of Morocco. Methods The data collected covers 3.6 millions inhabitant and included Casablanca city and the administrative region. Results The data collected in the years 2005-07 show that the top 5 forms of cancers in women were breast (ASR: 36.4 per 100,000), cervical (15.0), thyroid (6.7), colon-rectum (5.8), and ovarian (5.3); the top 5 cancers in men were lung (25.9), prostate (13.5), bladder (8.7), colon-rectum (8.1) and non-Hodgkin lymphoma (7.2). Tumours of haematopoietic and lymphoid tissues represented 11% of all cancers (skin excluded); some presented unusual sex ratios. For breast, cervical, colorectal and thyroid cancer, respectively 57%, 42%, 28% and 60% of the cases were under 50 years of age. This was attributable to particularly low numbers of cases recorded among old people, and the young age of the general population; the observed age-specific incidences under age 50 were not higher than in western countries. Cancers at young ages were particularly common in women: 67% of the cases were under 50. Stage at diagnosis could be obtained for 82% of the breast cancer cases and was as follows: 28% local, 63% regional and 9% distant, in the absence of screening. Conclusion These first population-based data have provided an invaluable resource for the national cancer control plan of Morocco, and will be useful tool to its future evaluation.

What doctors know about cancer pain management: an exploratory study in Sarawak, Malaysia.

Effective cancer pain management is influenced by the attitudes and knowledge of treating physicians. A survey was conducted among the total population of government hospital doctors of Sarawak to study the barriers to cancer pain management. Two hundred and fifty-three respondents (83%) completed the survey. The study results highlight that knowledge about cancer pain management was low and barriers to morphine prescription were high. A majority of doctors were deterred from using morphine because of fear of addiction (36.5%) and respiratory depression (53.1%). Only 16.2% of the doctors chose the oral mode of administration to treat pain, furthermore 25% prescribed morphine on “PRN” basis. Doctors with undergraduate study in oncology consistently answered better suggesting that the situation can be improved by education. This study showed that barriers to morphine prescription and knowledge deficit amongst government doctors in Sarawak are strong but similar to those reported in western countries few years ago.

Analysis of nasopharyngeal carcinoma risk factors with Bayesian networks

OBJECTIVES We propose a new graphical framework for extracting the relevant dietary, social and environmental risk factors that are associated with an increased risk of nasopharyngeal carcinoma (NPC) on a case-control epidemiologic study that consists of 1289 subjects and 150 risk factors. METHODS This framework builds on the use of Bayesian networks (BNs) for representing statistical dependencies between the random variables. We discuss a novel constraint-based procedure, called Hybrid Parents and Children (HPC), that builds recursively a local graph that includes all the relevant features statistically associated to the NPC, without having to find the whole BN first. The local graph is afterwards directed by the domain expert according to his knowledge. It provides a statistical profile of the recruited population, and meanwhile helps identify the risk factors associated to NPC. RESULTS Extensive experiments on synthetic data sampled from known BNs show that the HPC outperforms state-of-the-art algorithms that appeared in the recent literature. From a biological perspective, the present study confirms that chemical products, pesticides and domestic fume intake from incomplete combustion of coal and wood are significantly associated with NPC risk. These results suggest that industrial workers are often exposed to noxious chemicals and poisonous substances that are used in the course of manufacturing. This study also supports previous findings that the consumption of a number of preserved food items, like house made proteins and sheep fat, are a major risk factor for NPC. CONCLUSION BNs are valuable data mining tools for the analysis of epidemiologic data. They can explicitly combine both expert knowledge from the field and information inferred from the data. These techniques therefore merit consideration as valuable alternatives to traditional multivariate regression techniques in epidemiologic studies.

Nasopharyngeal Carcinoma Data Analysis with a Novel Bayesian Network Skeleton Learning Algorithm

In this paper, we discuss efforts to apply a novel Bayesian network (BN) structure learning algorithm to a real world epidemiological problem, namely the Nasopharyngeal Carcinoma (NPC). Our specific aims are : (1) to provide a statistical profile of the recruited population, (2) to help indentify the important environmental risk factors involved in NPC, and (3) to gain insight on the applicability and limitations of BN methods on small epidemiological data sets obtained from questionnaires. We discuss first the novel BN structure learning algorithm called Max-Min Parents and Children Skeleton (MMPC) developped by Tsamardinos et al. in 2005. MMPC was proved by extensive empirical simulations to be an excellent trade-off between time and quality of reconstruction compared to most constraint based algorithms, especially for the smaller sample sizes. Unfortunately, MMPC is unable to deal with datasets containing approximate functional dependencies between variables. In this work, we overcome this problem and apply the new version of MMPC on Nasopharyngeal Carcinoma data in order to shed some light into the statistical profile of the population under study.

Analysis of Nasopharyngeal Carcinoma Data with a Novel Bayesian Network Learning Algorithm

Learning the structure of a Bayesian network from a data set is NP-hard. In this paper, we discuss a novel heuristic called polynomial max-min skeleton (PMMS) developed by Tsamardinos et al. in 2005. PMMS was proved by extensive empirical simulations to be an excellent trade-off between time and quality of reconstruction compared to all constraint based algorithms, especially for the smaller sample sizes. Unfortunately, there are two main problems with PMMS : it is unable to deal with missing data nor with datasets containing functional dependencies between variables. In this paper, we propose a way to overcome these problems. The new version of PMMS is first applied on standard benchmarks to recover the original structure from data. The algorithm is then applied on the nasopharyngeal carcinoma (NPC) made up from only 1289 uncomplete records in order to shed some light into the statistical profile of the population under study.

Prevalence of mucosal and cutaneous human papillomavirus in Moroccan breast cancer

Background Due to recent technical improvements and some encouraging new results, there has been a resurgence of interest in the possibility that a substantial proportion of breast cancers (BCs) may be caused by viral infections, including Human papillomavirus (HPV). The aim of this study was to determine the prevalence of mucosal and cutaneous HPV in tumours from Moroccan BC patients. Materials and methods Frozen tumours from 76 BC cases and 12 controls were evaluated for the presence of 62 HPV-types using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. Results HPV DNA was found in 25.0% of BC tumours and only 8.3% of controls. Beta and gamma HPV types were found in 10.5% and 6.6% of BC tumours, respectively. High-risk mucosal types HPV16 and 18 were not detected in the subjects, but other probable/possible high-risk or high-risk -HPV types (HPV51, 52, 58, 59, and 66) were found in 5.3% of BC tumours. Statistical analysis showed no significant difference between, controls, BC cases and the inflammatory status (p > 0.05). Conclusion HPV DNA was found 3 times as frequently in the BC tumours as in the controls. However, this difference requires confirmation in a larger sample.