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47 result(s) for "Gaborieau, Valérie"
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A comprehensive analysis of excess depressive disorder in women and men living with HIV in France compared to the general population
We aimed to estimate the prevalence of depressive disorder in people living with HIV (PLWH) and evaluate its association with non-HIV-specific and HIV-specific factors in PLWH and in PLWH compared to the general population (GP). We used cross-sectional data from the QuAliV study, conducted within the ANRS-CO3 Aquitaine-AQUIVIH-NA cohort of PLWH in Nouvelle-Aquitaine (2018–2020), and a nationally-representative survey in the GP (EHIS-ESPS, 2014–2015), we included all participants aged ≥ 18 years old who had completed the Patient Health Questionnaire-8 (PHQ-8). Depressive disorder was defined as Patient Health Questionnaire-8 score greater or equal to 10. Its association with non-HIV-specific (demographic, socio-economic, behavioral, health status), HIV-specific factors (immuno-viral markers, antiretrovirals, level of perceived HIV-stigma), and HIV-status was assessed using Poisson regression models with robust variance in women and men separately. We included 914 PLWH (683 men/231 women). More than one in five PLWH had depressive disorder. It was strongly associated with being younger and experiencing severe pain in both sexes. Unemployment in women, being single, and lack of family ties in men were also associated with depressive disorder. More than 30% of our sample reported HIV-stigma, with a dose–response relationship between level of perceived HIV-stigma and depressive disorder. The crude prevalence of depressive disorder was 2.49 (95%CI 1.92–3.22) and 4.20 (95%CI 3.48–5.05) times higher in women and men living with HIV respectively compared to GP counterparts and 1.46 (95%CI 1.09–1.95) and 2.45 (95%CI 1.93–3.09) times higher after adjustment for non-HIV specific factors. The adjusted prevalence ratio of depressive disorder was not significantly different in HIV-stigma free women, but remained twice as high in HIV-stigma free men. The prevalence of depressive disorder compared to the GP tended to decrease with age in PLWH. Excess depressive disorder remains a major concern in PLWH. Our findings reaffirm the importance of regular screening. Tackling social inequalities and HIV-stigma should be prioritized to ensure that PLWH achieve good mental as well as physical health outcomes.
Disentangling the aetiological pathways between body mass index and site-specific cancer risk using tissue-partitioned Mendelian randomisation
BackgroundBody mass index (BMI) is known to influence the risk of various site-specific cancers, however, dissecting which subcomponents of this heterogenous risk factor are predominantly responsible for driving disease effects has proven difficult to establish. We have leveraged tissue-specific gene expression to separate the effects of distinct phenotypes underlying BMI on the risk of seven site-specific cancers.MethodsSNP-exposure estimates were weighted in a multivariable Mendelian randomisation analysis by their evidence for colocalization with subcutaneous adipose- and brain-tissue-derived gene expression using a recently developed methodology.ResultsOur results provide evidence that brain-tissue-derived BMI variants are predominantly responsible for driving the genetically predicted effect of BMI on lung cancer (OR: 1.17; 95% CI: 1.01–1.36; P = 0.03). Similar findings were identified when analysing cigarettes per day as an outcome (Beta = 0.44; 95% CI: 0.26–0.61; P = 1.62 × 10−6), highlighting a possible shared aetiology or mediator effect between brain-tissue BMI, smoking and lung cancer. Our results additionally suggest that adipose-tissue-derived BMI variants may predominantly drive the effect of BMI and increased risk for endometrial cancer (OR: 1.71; 95% CI: 1.07–2.74; P = 0.02), highlighting a putatively important role in the aetiology of endometrial cancer.ConclusionsThe study provides valuable insight into the divergent underlying pathways between BMI and the risk of site-specific cancers.
Immuno-related polymorphisms and cervical cancer risk: The IARC multicentric case-control study
A small proportion of women who are exposed to infection with human-papillomavirus (HPV) develop cervical cancer (CC). Genetic factors may affect the risk of progression from HPV infection to cervical precancer and cancer. We used samples from the International Agency for Research on Cancer (IARC) multicentric case-control study to evaluate the association of selected genetic variants with CC. Overall, 790 CC cases and 717 controls from Algeria, Morocco, India and Thailand were included. Cervical exfoliated cells were obtained from control women and cervical exfoliated cells or biopsy specimens from cases. HPV-positivity was determined using a general primer GP5+/6+ mediated PCR. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) of host genotypes with CC risk, using the homozygous wild type genotype as the referent category and adjusting by age and study centre. The association of polymorphisms with the risk of high-risk HPV-positivity among controls was also evaluated. A statistically significant association was observed between single nucleotide polymorphism (SNP) CHR6 rs2844511 and CC risk: the OR for carriers of the GA or GG genotypes was 0.70 (95% CI: 0.43-1.14) and 0.61 (95% CI: 0.38-0.98), respectively, relative to carriers of AA genotype (p-value for trend 0.03). We also observed associations of borderline significance with the TIPARP rs2665390 polymorphism, which was previously found to be associated with ovarian and breast cancer, and with the EXOC1 rs13117307 polymorphism, which has been linked to cervical cancer in a large study in a Chinese population. We confirmed the association between CC and the rs2844511 polymorphism previously identified in a GWAS study in a Swedish population. The major histocompatibility region of chromosome 6, or perhaps other SNPs in linkage disequilibrium, may be involved in CC onset.
Genetic Variants in Nicotine Addiction and Alcohol Metabolism Genes, Oral Cancer Risk and the Propensity to Smoke and Drink Alcohol: A Replication Study in India
Genetic variants in nicotinic acetylcholine receptor and alcohol metabolism genes have been associated with propensity to smoke tobacco and drink alcohol, respectively, and also implicated in genetic susceptibility to head and neck cancer. In addition to smoking and alcohol, tobacco chewing is an important oral cancer risk factor in India. It is not known if these genetic variants influence propensity or oral cancer susceptibility in the context of this distinct etiology. We examined 639 oral and pharyngeal cancer cases and 791 controls from two case-control studies conducted in India. We investigated six variants known to influence nicotine addiction or alcohol metabolism, including rs16969968 (CHRNA5), rs578776 (CHRNA3), rs1229984 (ADH1B), rs698 (ADH1C), rs1573496 (ADH7), and rs4767364 (ALDH2). The CHRN variants were associated with the number of chewing events per day, including in those who chewed tobacco but never smoked (P =  0.003, P =  0.01 for rs16969968 and rs578776 respectively). Presence of the variant allele contributed to approximately 13% difference in chewing frequency compared to non-carriers. While no association was observed between rs16969968 and oral cancer risk (OR =  1.01, 95% CI =  0.83- 1.22), rs578776 was modestly associated with a 16% decreased risk of oral cancer (OR =  0.84, 95% CI =  0.72- 0.98). There was little evidence for association between polymorphisms in genes encoding alcohol metabolism and oral cancer in this population. The association between rs16969968 and number of chewing events implies that the effect on smoking propensity conferred by this gene variant extends to the use of smokeless tobacco.
Tobacco consumption and genetic susceptibility to nasopharyngeal carcinoma (NPC) in Thailand
Background: The incidence of nasopharyngeal carcinoma (NPC) varies substantially worldwide, with an endemic pocket in Southeast Asia. Method: We assessed lifestyle and genetic factors in relation to NPC risk among 681 NPC cases and 1,078 controls from Thailand. Evaluated lifestyle factors included traditionally preserved foods, tobacco smoking, betel quid chewing, and alcohol consumption. Genetic factors included six variants implicated in a previous a genome-wide association study (GWAS) of NPC and three variants residing near the CHRNA3 and TERT genes that were linked to lung cancer risk in Asian populations. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated using unconditional logistic regression. Results: Frequent consumption of fermented vegetables was associated with increased NPC risk (OR of consumption >weekly vs.
Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer
Paul Brennan and colleagues perform genome-wide association analysis for oral cavity and pharyngeal cancer in trans-ancestry populations. They find seven new loci across different cancer subtypes, including a protective association in the HLA region that has a stronger effect in patients with human papillomavirus–positive cancers. We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci ( P < 5 × 10 −8 ), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1 ), 10q26.13 (rs201982221, LHPP ) and 11p15.4 (rs1453414, OR52N2 – TRIM5 ). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1 ) and 9q34.12 (rs928674, LAMC3 ), and with known cancer-related loci—9p21.3 (rs8181047, CDKN2B-AS1 ) and 5p15.33 (rs10462706, CLPTM1L ). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301–HLA-DQA1*0103–HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10 −9 ). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10 −6 ) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
The complexity of tobacco smoke-induced mutagenesis in head and neck cancer
Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). We explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC samples from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and alcohol-related signatures, indicating a combined effect of these exposures. Tobacco smoking was associated with differences in the mutational spectra, repertoire of driver mutations in cancer genes and patterns of copy number change. Our results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones. Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.
Needlestack: an ultra-sensitive variant caller for multi-sample next generation sequencing data
The emergence of next-generation sequencing (NGS) has revolutionized the way of reaching a genome sequence, with the promise of potentially providing a comprehensive characterization of DNA variations. Nevertheless, detecting somatic mutations is still a difficult problem, in particular when trying to identify low abundance mutations, such as subclonal mutations, tumour-derived alterations in body fluids or somatic mutations from histological normal tissue. The main challenge is to precisely distinguish between sequencing artefacts and true mutations, particularly when the latter are so rare they reach similar abundance levels as artefacts. Here, we present needlestack, a highly sensitive variant caller, which directly learns from the data the level of systematic sequencing errors to accurately call mutations. Needlestack is based on the idea that the sequencing error rate can be dynamically estimated from analysing multiple samples together. We show that the sequencing error rate varies across alterations, illustrating the need to precisely estimate it. We evaluate the performance of needlestack for various types of variations, and we show that needlestack is robust among positions and outperforms existing state-of-the-art method for low abundance mutations. Needlestack, along with its source code is freely available on the GitHub platform: https://github.com/IARCbioinfo/needlestack.
Associations of lifestyle and diet with the risk of nasopharyngeal carcinoma in Singapore: a case–control study
Background Nasopharyngeal carcinoma (NPC) is a commonly diagnosed cancer in Southeast Asia. Many studies have examined the risk factors for NPC, yet the roles of some risk factors remain inconclusive. The purpose of this study was to examine associations between modifiable lifestyle factors and the risk of NPC in the Singaporean population. Methods We conducted a case–control study in Singapore with 300 patients and 310 controls who were recruited between 2008 and 2012. Each control was selected and individually matched to each patient based on sex, ethnicity, and age (±5 years). A total of 290 pairs of cases and controls were matched successfully. We examined lifestyle factors such as tobacco smoking, alcohol drinking, various salted and preserved food consumption, and weaning practices. Results After adjusting for covariates, multivariate analysis showed that those participants who were current smokers and had ever smoked tobacco had a higher risk of NPC than participants who had never smoked, with odds ratios (ORs) of 4.50 (95% confidence interval [CI] 2.58–7.86; P < 0.001) and 2.52 (95% CI 1.54–4.12; P < 0.001), respectively. Those who consumed salted vegetables at least once a week also showed a significantly increased risk of NPC than those who never or rarely consumed salted vegetables, with an OR of 4.18 (95% CI 1.69–10.38; P = 0.002). Conclusion Smoking (currently and ever‐smoked) and consuming salted vegetables once a week or more were lifestyle risk factors for NPC, and changes of these factors for the better may reduce the risk of NPC.