Meriem Khyatti

Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa

Background:The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known.Methods:From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regression was used to evaluate the association of lifestyles with NPC risk, controlling for socioeconomic status and dietary risk factors.Results:Cigarette smoking and snuff (tobacco powder with additives) intake were significantly associated with differentiated NPC but not with undifferentiated carcinoma (UCNT), which is the major histological type of NPC in these populations. As demonstrated by a stratified permutation test and by conditional logistic regression, marijuana smoking significantly elevated NPC risk independently of cigarette smoking, suggesting dissimilar carcinogenic mechanisms between cannabis and tobacco. Domestic cooking fumes intake by using kanoun (compact charcoal oven) during childhood increased NPC risk, whereas exposure during adulthood had less effect. Neither alcohol nor shisha (water pipe) was associated with risk.Conclusion:Tobacco, cannabis and domestic cooking fumes intake are risk factors for NPC in western North Africa.

Dietary risk factors for nasopharyngeal carcinoma in Maghrebian countries

North Africa is one of the major Nasopharyngeal Carcinoma (NPC) endemic regions. Specific food items unique to this area were implicated to be associated with NPC risk, but results were inconsistent. Here we have performed a large‐scale case‐control study in the Maghrebian population from Tunisia, Algeria and Morocco. From 2002 to 2005, interviews were conducted on 636 cases and 615 controls. Controls were hospitalized individuals from 15 non‐cancer hospital departments, or friends and family members of non‐NPC cancer subjects, matched by center, childhood household type (rural or urban), age and sex. Conditional logistic regression is used to evaluate the risk of factors. In results, consumption of rancid butter, rancid sheep fat and preserved meat not spicy (mainly quaddid) were associated with significantly increased risk of NPC, while consumption of cooked vegetables and industrial preserved fish was associated with reduced risk. Other foods such as fresh citrus fruits and spicy preserved meat (mainly osban) in childhood, industrial made olive condiments in adulthood, were marginally associated. In multivariate analyses, only rancid butter, rancid sheep fat and cooked vegetables were significantly associated with NPC. In regard to possible causative substances, our results implicate the involvement of butyric acid, a potential Epstein‐Barr virus (EBV) activator.

Antibodies to the Epstein-Barr virus transactivator protein (ZEBRA) as a valuable biomarker in young patients with nasopharyngeal carcinoma.

Epstein‐Barr virus (EBV)–associated nasopharyngeal carcinoma (NPC) generally occurs in adults, especially in high‐prevalence populations such as the Chinese and Eskimos. In Maghrebian populations, young patients affected with this malignancy represent 25% of the total NPC cases. In adults with NPC, relatively high titers of IgA antibodies to the EBV viral capsid antigen (VCA) and early antigen (EA) represent important markers. However, nearly 50% of young NPC patients are negative for IgA‐anti‐VCA and ‐EA or exhibit very low titers of these antibodies. We report here that 92% of sera from young NPC patients negative for IgA‐EA and 89% of those negative for IgA‐VCA were positive for IgG antibodies to the EBV transactivator protein (ZEBRA) at very high titers. Our results show that in young patients with NPC these antibodies represent the most reliable marker for diagnosis and prognosis, particularly when compared with conventional NPC markers, i.e., IgA‐VCA (58%) and anti‐EA (25%). The titers of IgG‐ZEBRA antibodies increased along with lymph node involvement only in the young patient group, suggesting a prognostic value of this marker in this patient group. Int. J. Cancer 86:71–75, 2000.

Study of human leukocyte antigen class I phenotypes in Moroccan patients with nasopharyngeal carcinoma.

Previous reports demonstrated an association between the human leukocyte antigen (HLA) and risk for nasopharyngeal carcinoma (NPC) among the Chinese in Singapore, a population with a high incidence of this malignancy. In our study, we assess the association between HLA and NPC in Morocco, a median‐prevalence area for this cancer, where NPC presents the particularity of also affecting young individuals. Using the standard microlympho‐cytotoxicity test, we typed a total of 154 Moroccan NPC patients and 257 unrelated healthy controls for their HLA‐A and B antigens. The results of these analyses show that the frequencies of HLA‐A10, HLA‐B13 and HLA‐B18 were found to be higher in the NPC group than in the control group, whereas HLA‐A9 was associated with a decreased risk. After correction for the number of specificities tested, these differences were statistically significant only for HLA‐B18 (corrected p value [pc] < 0.023, relative risk [RR] = 4.14) and HLA‐A9 (pc < 0.023, RR = 0.45). The comparison of the distribution of the HLA antigens in younger and older cohorts of patients shows that the incidence of HLA‐A10 and HLA‐ B18 was higher in the older group, whereas the frequencies of HLA‐A19 and HLA‐B13 were significantly higher in younger patients compared with controls. The presence of both HLA‐A19 and HLA‐B13 phenotypes correlated with an increased risk of developing NPC among overall patients compared with controls. According to the sex distribution, increased frequency of HLA‐B18 was found in male and female NPC patients compared with controls, whereas the frequency of HLA‐A10 was higher only in male NPC patients compared with controls.

Antibody Responses to Recombinant Epstein-Barr Virus Antigens in Nasopharyngeal Carcinoma Patients: Complementary Test of ZEBRA Protein and Early Antigens p54 and p138

ABSTRACT Serological tests based on the antibodies directed against the Epstein-Barr virus early antigen (EA) and viral capsid antigen (VCA), which have been recognized as tumor markers for nasopharyngeal carcinoma (NPC), are routinely used to help in the diagnosis of this malignancy. The detection of these antibodies reveals very low titers, found only in a small proportion of young compared with older NPC patients. This is a problem for the diagnosis of NPC, especially among Maghrebians, among whom young people are also affected, and emphasizes the necessity to search for more reliable markers. The present study reports results of immunoglobulin G (IgG) and IgA responses of NPC patients to recombinant EA antigens p54 (BMRF1) and p138 (BALF2), VCA complex antigens p18 (BFRF3) and p23 (BLRF2), and EBNA antigen p72 (BKRF1). Our results show that IgA-EA-p54 and -p138 (IgA-EA-p54+138) antibodies have a diagnostic value for detection of NPC (70%), compared with IgA-VCA-p18+23 and IgA-EBNA-p72, which have limited diagnostic value, especially in young patients. It is also noteworthy that IgA-EA-p54+138 can detect a high percentage (64%) of NPC cases negative by immunofluorescence. These results, however, clearly show that a single test cannot achieve the objective of detecting all NPC patients, and it seems advisable to combine different tests for the diagnosis of NPC. The combination of IgG-ZEBRA with IgA-EA-p54+138 improved the sensitivity of detection of NPC to 95% in the overall NPC population. The use of IgA-EA-p54+138 in combination with IgG-ZEBRA will facilitate detailed studies on the pattern of antibody response, which may result in the development of useful serological markers to guide the treatment of NPC.

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.

Human papillomavirus detection in moroccan patients with nasopharyngeal carcinoma

BackgroundNasopharyngeal carcinoma (NPC) is a malignant tumor which arises in surface epithelium of the posterior wall of the nasopharynx. Theres is evidence that Epstein Barr virus (EBV) is associated to NPC development. However, many epidemiologic studies point to a connection between viral infections by the human papillomavirus (HPV) and NPC.MethodSeventy Moroccan patients with NPC were screened for EBV and HPV. EBV detection was performed by PCR amplification of BZLF1 gene, encoding the ZEBRA (Z Epstein-Barr Virus Replication Activator) protein, and HPV infection was screened by PCR amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 35, 45 and 59.ResultsThe age distribution of our patients revealed a bimodal pattern. Sixty two cases (88.9%) were classified as type 3 (undifferentiated carcinoma), 6 (8.6%) as type 2 (non keratinizing NPC) and only 2 (2.9%) cases were classified as type 1 (keratinizing NPC). EBV was detected in all NPC tumors, whereas HPV DNA was revealed in 34% of cases (24/70). Molecular analysis showed that 20.8% (5/24) were infected with HPV31, and the remaining were infected with other oncogenic types (i.e., HPV59, 16, 18, 33, 35 and 45). In addition, statistical analysis showed that theres no association between sex or age and HPV infection (P > 0.1).ConclusionOur data indicated that EBV is commonly associated with NPC in Moroccan patients and show for the first time that NPC tumours from Moroccan patients harbour high risk HPV genotypes.

Prevalence of overweight and obesity in adults from North Africa.

The share of North African immigrants in Europe is growing continuously. In this review, we aimed to systematically analyse and describe the literature on weight status and physical activity in North African adults, both in their home country and after immigration to Europe. Existing data on North African residents and on North African immigrants in Europe were analysed by a systematic search on PUBMED. There is a wide variation among countries in the prevalence of overweight/obesity, with immigrants showing higher values. The overall results revealed a higher prevalence of overweight and obesity in females than in males in North African residents. Females also show higher levels of obesity among immigrants. In particular, literature reports indicate that 1.3-47.8% of North African residents and 3.6-49.4% of North African immigrants in adult age are overweight or obese. Physical inactivity is higher than 20% in males and 40% in females in North African residents. The highest frequency of physically inactive or lightly active people among immigrants was observed in first-generation Sudanese and Moroccans in Amsterdam (males: 57.1%; females: 74.2%), with increasing rates in second-generation females. The results underline a higher health risk in North African immigrants than in residents. Specific public health strategies should be adopted in various populations of North African origin to control the obesity epidemic.

Obesity and physical activity in children of immigrants

Childhood overweight and obesity have increased in recent decades, reaching alarming proportions. Children with a migrant background seem to be particularly at risk of developing overweight and obesity. This article provides an overview of the prevalence of overweight or obesity among North African (NA) children living in their own countries or as immigrants in Europe. The aim is to show the effect of the migration process on this trend and to discuss its possible contributing factors. Publications were identified by a systematic search of PubMed and the existing literature. Original longitudinal or cross-sectional studies on the prevalence of childhood and adolescent overweight and obesity and of physical activity among ethnic groups from North Africa compared with the native population were reviewed. The results confirmed that children of NA origin in Europe have higher levels of overweight and obesity than the native ones, especially girls. However, this trend can also be detected in urban areas of NA countries. Important factors contributing to the increase of overweight and obesity among children and adolescents are discussed, in particular the westernization of eating habits, the level of physical activity and body image perception. The review shows that factors linked to acculturation in the host society and others maintained from the country of origin come into play in determining childhood overweight and obesity among NA immigrants in Europe. The importance of health promotion targeting the groups most at risk of childhood overweight and obesity, i.e. aspects of a healthy diet and the benefits of physical activity, is underlined.

Analysis of mutations in the E6 oncogene of human papillomavirus 16 in cervical cancer isolates from Moroccan women

BackgroundWorldwide, cervical cancer is the second most common cancer in women. High-risk human papillomavirus (HPV) play a crucial role in the etiology of cervical cancer and the most prevalent genotype is HPV16. HPV 16 intratypic variants have been reported to differ in their prevalence, biological and biochemical properties. The present study was designed to analyze and identify HPV type 16 E6 variants among patients with cervical cancer in Morocco.MethodsA total of 103 HPV16 positive samples were isolated from 129 cervical cancer cases, and variant status was subsequently determined by DNA sequencing of the E6 gene.ResultsIsolates from patients were grouped into the European (E), African (Af) and North-American (NA1) phylogenetic clusters with a high prevalence of E lineage (58.3%). The Af and NA1 variants were detected in 31.1% and 11.6% of the HPV16 positive specimens, respectively, whereas, only 3% of cases were prototype E350T. No European-Asian (EA), Asian (As) or Asian-American (AA) variants were observed in our HPV16-positive specimens. At the amino acid level, the most prevalent non-synonymous variants were L83V (T350G), H78Y (C335T), E113D (A442C), Q14D (C143G/G145T) and R10I (G132T), and were observed respectively in 65%, 41.8%, 38.8%, 30.1% and 23.3% of total samples.Moreover, HPV16 European variants were mostly identified in younger women at early clinical diagnosis stages. Whereas, HPV16 Af variants were most likely associated with cervical cancer development in older women with pronounced aggressiveness.ConclusionThis study suggests a predominance of E lineage strains among Moroccan HPV 16 isolates and raises the possibility that HPV16 variants have a preferential role in progression to malignancy and could be associated with the more aggressive nature of cervical cancer.