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: Cancer & Population. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Abstract: Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10 27 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p=1.30610 211 ). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p=5.38610 211 ). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p=2.60610 220 , allelic risk=1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1LTERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK)

Abstract: Objective To estimate the risk of breast cancer associated with diagnostic radiation in carriers of BRCA1/2 mutations. Design Retrospective cohort study (GENE-RAD-RISK). Setting Three nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands, Participants 1993 female carriers of BRCA1/2 mutations recruited in 2006-09. Main outcome measure Risk of breast cancer estimated with a weighted Cox proportional hazards model with a time dependent individually estimated cumulative breast dose, based on nominal estimates of organ dose and frequency of self reported diagnostic procedures. To correct for potential survival bias, the analysis excluded carriers who were diagnosed more than five years before completion of the study questionnaire. Results In carriers of BRCA1/2 mutations any exposure to diagnostic radiation before the age of 30 was associated with an increased risk of breast cancer (hazard ratio 1.90, 95% confidence interval 1.20 to 3.00), with a dose-response pattern. The risks by quarter of estimated cumulative dose Conclusion In this large European study among carriers of BRCA1/2 mutations, exposure to diagnostic radiation before age 30 was associated with an increased risk of breast cancer at dose levels considerably lower than those at which increases have been found in other cohorts exposed to radiation. The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations.

Alcohol intake and colorectal cancer risk: A dose–response meta‐analysis of published cohort studies

Abstract: The epidemiologic evidence support that alcohol intake might be associated with increased colorectal cancer risk. However, the results by anatomic site in the large bowel are inconsistent. We conducted a meta-analysis of prospective cohort studies published between 1990 and June 2005 on the relationship between alcohol intake and colon and rectal cancer. We quantified associations with colon and rectal cancer using meta-analysis of relative risk (RR) associated to the highest versus the lowest category of alcohol intake and meta-analysis of study-specific dose-response slopes using fixed or random effect models depending on the heterogeneity of effects among studies. Sixteen prospective cohort studies including more than 6,300 patients with colorectal cancer were eligible for inclusion. High alcohol intake was significantly associated with increased risk of colon (RR = 1.50; 95% CI = 1.25, 1.79) and rectal cancer (RR = 1.63; 95% CI = 1.35, 1.97) when comparing the highest with the lowest category of alcohol intake, equivalent to a 15% increase of risk of colon or rectal cancer for an increase of 100 g of alcohol intake per week. The relationship did not differ significantly by anatomical site (colon, rectum). Using meta-regression analysis, we identified geographical area where the study was conducted as a possible source of between-study heterogeneity of effects among studies. Lifestyle recommendations for prevention of colorectal cancer should consider limiting alcohol intake.

1,N6-Ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine in liver DNA from humans and untreated rodents detected by immunoaffinity/32P-postlabelling

Abstract: The etheno-bridged exocyclic DNA adducts 1,N6-ethenodeoxyadenosine (epsilon dA) and 3,N4-ethenodeoxycytine (epsilon dC) can be formed by several structurally diverse carcinogens and mutagens that include vinyl chloride and urethane In order to investigate the occurrence and persistence of these adducts in rodents exposed to such DNA-damaging agents, an ultra-sensitive detection method has been developed It is based on immunoaffinity purification of the etheno adducts and subsequent 32P-postlabelling followed by separation as 5'-monophosphates on polyethyleneimine-cellulose-coated thin-layer plates Normal nucleotides in the DNA samples were quantitated by HPLC Optimal conditions for enzymatic hydrolysis of DNA are described: deoxyuridine 3'-monophosphate was used as internal standard to correct for labelling efficiency of the etheno adducts The method had a detection limit of 25 amol of epsilon dA and epsilon dC for a 50 micrograms DNA sample Using this technique, analysis of liver DNA from humans with unknown exposure revealed the presence of epsilon dA and epsilon dC residues in the range of 0-27 adducts per 10(9) parent bases Liver DNA obtained from untreated mice and rats was also shown to contain similar low but variable levels of these etheno adducts In vitro studies indicated that these promutagenic DNA lesions could arise from endogenously formed lipid peroxidation products

Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

Abstract: Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.