International Agency for Research on Cancer

About: International Agency for Research on Cancer is a government organization based out in Lyon, France. It is known for research contribution in the topics: Population & Cancer. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.

Mutagenic and alkylating metabolites of halo-ethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver tissues. Evidence for oxirane formation by P450-linked microsomal mono-oxygenases.

Abstract: Mutagenicity, expressed as the number of his + revenants per μmole of test compound per hour of exposure, was estimated in two strains of S. typhimurium in the presence of a postmitochondrial mouse-liver supernatant, following exposure to vapours of one of a series of halo-olefins. Their activity was in the following descending order: 3,4-dichlorobutene-1 > 1-chlorobutadiene (technical grade) > 2-chlorobutadiene > vinyl bromide > vinylidene chloride > vinyl chloride; marginal mutagenicity was detected in the presence of 1,1,2-trichloroethylene and 1,1-difluoroethylene, and none with tetrachloroethylene and vinyl acetate. Liver fractions from humans converted vinyl chloride, vinyl bromide, vinylidene chloride and 2-chlorobutadiene into mutagens. In the plate incorporation assay, 1,4-dichlorobutene-2 was mutagenic per se, and addition of microsomal fractions from human or mouse liver enhanced the mutagenicity; a synthetic putative metabolite, 1,4-dichloro-2,3-epoxybutane was less mutagenic than the parent olefin in strain TA100. Treatment of rats with phenobarbital or 3-methylcholanthrene caused an up to 2-fold increase in the liver microsome-mediated mutagenicities of vinyl chloride and vinylidene chloride in S. typhimurium TA1530; while treatment with pregnenolone-16α-carbonitrile, aminoacetonitrile or disulfiram decreased the mutagenic effects. Vinyl chloride, and probably vinyl bromide, were shown to be epoxidized by mouse-liver microsomes; volatile alkylating metabolites were trapped by reaction with excess 4-(4-nitrobenzyl)pyridine and analysed spectrally. 2-Chlorobutadiene also yielded an alkylating intermediate, but 1,1-difluoroethylene, 1,1-dichloroethyleneand 1,1,2-trichloroethylene did not. 2-Chloro- and 1-chlorobutadiene, 3,4-dichlorobutene-1, 1,4-dichlorobutene-2 and its 2,3-epoxy derivative showed alkylating activity with 4-(4-nitrobenzyl)pyridine, which was not related quantitatively to mutagenic activity in S. typhimurium TA100 in the absence of a metabolic activation system. These data support the hypothesis that an oxidation of the double bond in certain halo-olefins, which is dependent on microsomal mono-oxygenases is a common pathway in the formation of biologically reactive intermediates. The relevance of the metabolites formed during such oxidative processes to the mutagenic, toxic and carcinogenic activities in vivo of some of the parent compounds is discussed.

Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

Abstract: Background: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. Methods and Findings: The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prenticeweighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction = 1.20610 24 ). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.50610 23 ) and waist circumference (p for interaction = 7.49610 29 ). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. Conclusions: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this subgroup is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention. Please see later in the article for the Editors’ Summary.

Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid

Abstract: Lancet Oncology, The - In Press.Proof corrected by the author Available online since mercredi 24 juin 2015

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

Abstract: Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.

Conformity to traditional Mediterranean diet and cancer incidence: the Greek EPIC cohort

Abstract: Adherence to traditional Mediterranean diet (MD) has been reported to be inversely associated with total, as well as cardiovascular, mortality. We have examined the relation between degree of such adherence and incidence of cancer overall in a general population sample of 25 623 participants (10 582 men, 15 041 women) of the Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). All subjects completed a validated, interviewer-administered, semi-quantitative food-frequency questionnaire at enrolment. Degree of adherence to the traditional MD was assessed through a 10-point scale (0 minimal; 9 maximal) that incorporated key dietary characteristics. During a median follow-up of 7.9 years and 188 042 total person-years, 851 medically confirmed incident cancer cases (421 men, 430 women) were recorded. Using proportional hazards regression with adjustment for potential confounders, we found that a higher degree of MD adherence was associated with lower overall cancer incidence. A two-point increase in the score corresponded to a 12% reduction in cancer incidence (adjusted hazard ratio, 0.88 (95% confidence interval 0.80, 0.95)). The association was exposure-dependent and stronger among women. This inverse association with MD adherence was considerably stronger than that predicted on the basis of the associations of the individual components of this diet and points to the value of analysing dietary patterns in cancer studies.