Etiologie

Facteurs exogènes : Exposition professionnelle

Menée en Norvège sur la période 1953-2008, cette étude analyse l'évolution de l'incidence du cancer du poumon chez des salariés d'industries utilisant du carbure de silicium

Lung cancer incidence among Norwegian silicon carbide industry workers: associations with particulate exposure factors
• Occupational and Environmental Medicine, sous presse, 2012 (résumé)

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Menée en Norvège sur la période 1953-2008, cette étude analyse l'évolution de l'incidence du cancer du poumon chez des salariés d'industries utilisant du carbure de silicium

“Lung cancer incidence among Norwegian silicon carbide industry workers: associations with particulate exposure factors”

• Bugge, Merete Drevvatne;Kjærheim, Kristina;Føreland, Solveig;Eduard, Wijnand;Kjuus, Helge

Objectives An increased lung cancer risk associated with total dust exposure in the silicon carbide (SiC) industry has previously been reported. The aim of the present study was to examine the relative importance of specific exposure factors by using a comprehensive, historic job exposure matrix based on about 8000 measurements.Methods Cumulative exposure to total and respirable dust, respirable quartz, cristobalite, and SiC particles and SiC fibres was assessed for 1687 long-term workers employed during 1913–2003 in the Norwegian SiC industry. Standardised incidence ratios for lung cancer, with follow-up during 1953–2008, were calculated stratified by cumulative exposure categories. Poisson regression analyses were performed using both categorised and log-transformed cumulative exposure variables.Results The lung cancer incidence was about twofold increased at the highest level of exposure to each of the exposure factors (standardised incidence ratios 1.9–2.3 for all agents). ...

Mots clés : Poumon; Etiologie (Facteurs exogènes : Exposition professionnelle)

Facteurs exogènes : Autres

Menée sur 40 451 participantes (durée de suivi : supérieure à 10 ans), cette étude de cohorte canadienne évalue l'association entre le port d'implants mammaires esthétiques et le risque de cancer du sein

Canadian breast implant cohort: Extended follow-up of cancer incidence
• International Journal of Cancer, sous presse, 2012 (résumé)

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Menée sur 40 451 participantes (durée de suivi : supérieure à 10 ans), cette étude de cohorte canadienne évalue l'association entre le port d'implants mammaires esthétiques et le risque de cancer du sein

“Canadian breast implant cohort: Extended follow-up of cancer incidence”

• Pan, Sai Yi;Lavigne, Eric;Holowaty, Eric J.;Villeneuve, Paul J.;Xie, Lin;Morrison, Howard;Brisson, Jacques

Cosmetic breast implants are not associated with increased breast cancer incidence, but variations of risk according to implant characteristics are still poorly understood. As well, the assessment of cancer risk for sites other than breast needs to be clarified. The purpose of this study was to fill these research gaps. This study presents an extended analysis of 10 more years of follow-up of a large Canadian cohort of women who received either cosmetic breast implants (n = 24,558) or other cosmetic surgery (15,893). Over 70% of the implant cohort was followed for over 20 years. Cancer incidence among implant women was compared to those of controls using multivariate Poisson models and the general female population using the standardized incidence ratios (SIRs). Women with breast implants had reduced rates of breast and endometrial cancers compared to other surgery women. Subglandular implants were associated to a reduced rate of breast cancer compared to submuscular implants ...

Mots clés : Sein; Etiologie (Facteurs exogènes : Autres)

A partir d'une revue de la littérature (44 articles), cette étude évalue l'association entre une radiothérapie et le risque d'angiosarcome de la prostate

Prostate angiosarcoma: is there any association with previous radiation therapy ?
• BJU International, sous presse, 2012 (résumé)

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A partir d'une revue de la littérature (44 articles), cette étude évalue l'association entre une radiothérapie et le risque d'angiosarcome de la prostate

“Prostate angiosarcoma: is there any association with previous radiation therapy ?”

• Khaliq, Waseem;Meyer, Christian;Uzoaru, Ikechukwu;Wolf, Richard;Antonarakis, Emmanuel

What's known on the subject ? and What does the study add ? Angiosarcomas are histological subtype of sarcomas and rarely involve the prostate gland. Only ten cases of prostate angiosarcoma have been reported in the literature to date. Occurrence of post-irradiation prostate angiosarcoma is rare considering the frequency of radiotherapy used for treatment of prostate adenocarcinoma. We provide a brief review of all cases of prostate angiosarcoma and describe the epidemiology, etiology, clinical presentation, histopathology, prognostic factors and current treatment options for prostate angiosarcoma. For the current review a literature search was carried out using Pubmed, EmBase, and Cochrane databases. All cases of prostate angioscaroma reported to date and observational studies evaluating the radiation associated cancer occurrence were reviewed. Despite the rarity, prostate angiosarcomas display remarkable clinical and pathological heterogeneity, and a treatment challenge. We found ...

Mots clés : Prostate; Etiologie (Facteurs exogènes : Autres)

Menée entre 2000 et 2002 à partir d'un questionnaire auprès de 75 546 résidents de l'Etat de Washington (âge : 50 à 76 ans), cette étude évalue l'association entre la fréquence d'utilisation de médicaments anti-inflammatoires non stéroïdiens sur une durée de 10 ans et le risque de cancer du poumon à petites cellules

Non-steroidal anti-inflammatory drugs and small cell lung cancer risk in the VITAL study
• Lung Cancer, sous presse, 2012 (résumé)

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Menée entre 2000 et 2002 à partir d'un questionnaire auprès de 75 546 résidents de l'Etat de Washington (âge : 50 à 76 ans), cette étude évalue l'association entre la fréquence d'utilisation de médicaments anti-inflammatoires non stéroïdiens sur une durée de 10 ans et le risque de cancer du poumon à petites cellules

“Non-steroidal anti-inflammatory drugs and small cell lung cancer risk in the VITAL study”

• Brasky, Theodore M.;Baik, Christina S.;Slatore, Christopher G.;Potter, John D.;White, Emily

Few studies have examined the association between non-steroidal anti-inflammatory drug (NSAID) use and risk of small cell lung cancer (SCLC); among them, findings are mixed. Recently, we found that use of NSAIDs was differentially associated with lung cancer risk by histology. Here, we examine, more comprehensively, the association between individual NSAIDs and SCLC risk. 75,546 residents of western Washington State, ages 50–76, completed a baseline questionnaire in 2000–2002 and reported on their use of individual NSAIDs over the past 10 years. NSAID use was categorized as non-users, low (<4 days/week or <4 years), and high (≥4 days/week and ≥4 years). 111 SCLC were identified through linkage to a population-based cancer registry. Multivariable-adjusted Cox proportional hazards models including strong adjustment for smoking were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Compared to non-use, high use of regular-strength aspirin was associated ...

Mots clés : Poumon; Etiologie (Facteurs exogènes : Autres)

Facteurs endogènes

A partir de données de l'étude EPIC portant sur 343 765 femmes et 146 824 hommes, cette étude évalue l'association entre différentes mesures corporelles et le risque de carcinome différencié de la thyroïde (566 cas)

Body size and risk of differentiated thyroid carcinomas: Findings from the EPIC study
• International Journal of Cancer, sous presse, 2012 (résumé)

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A partir de données de l'étude EPIC portant sur 343 765 femmes et 146 824 hommes, cette étude évalue l'association entre différentes mesures corporelles et le risque de carcinome différencié de la thyroïde (566 cas)

“Body size and risk of differentiated thyroid carcinomas: Findings from the EPIC study”

• Rinaldi, Sabina;Lise, Mauro;Clavel-Chapelon, Françoise;Boutron-Ruault, Marie-Christine;Guillas, Gwenaelle;Overvad, Kim;Tjønneland, Anne;Halkjær, Jytte;Lukanova, Annekatrin;Kaaks, Rudolf;Bergmann, Manuela M.;Boeing, Heiner;Trichopoulou, Antonia;Zylis, Dimosthenis;Valanou, Elissavet;Palli, Domenico;Agnoli, Claudia;Tumino, Rosario;Polidoro, Silvia;Mattiello, Amalia;Bas Bueno-de-Mesquita, H.;Peeters, Petra H.;Weiderpass, Elisabete;Lund, Eiliv;Skeie, Guri;Rodríguez, Laudina;Travier, Noemie;Sánchez, Maria-José;Amiano, Pilar;Huerta, José-María;Ardanaz, Eva;Rasmuson, Torgny;Hallmans, Göran;Almquist, Martin;Manjer, Jonas;Tsilidis, Konstantinos K.;Allen, Naomi E.;Khaw, Kay-Tee;Wareham, Nick;Byrnes, Graham;Romieu, Isabelle;Riboli, Elio;Franceschi, Silvia

Results from case-control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow-up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m2) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03–1.94); height (HR = 1.61; 95% CI: 1.18–2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00–1.79) and waist-to-hip ratio (HR = 1.42, 95% CI: 1.05–1.91). The association with BMI was somewhat stronger in women below age 50. ...

Mots clés : Thyroïde; Etiologie (Facteurs endogènes)

Menée sur 46 échantillons tumoraux prélevés sur des patients atteints d'un carcinome papillaire thyroïdien, cette étude identifie un polymorphisme à simple nucléotide, situé sur le chromosome 14q13.3, en association avec ce cancer et met en évidence un mécanisme explicatif impliquant un gène de large ARN non codant intergénique (PTCSC3)

The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type
• Proceedings of the National Academy of Sciences, sous presse, 2012 (résumé)

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Menée sur 46 échantillons tumoraux prélevés sur des patients atteints d'un carcinome papillaire thyroïdien, cette étude identifie un polymorphisme à simple nucléotide, situé sur le chromosome 14q13.3, en association avec ce cancer et met en évidence un mécanisme explicatif impliquant un gène de large ARN non codant intergénique (PTCSC3)

“The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type”

• Jendrzejewski, Jaroslaw;He, Huiling;Radomska, Hanna S.;Li, Wei;Tomsic, Jerneja;Liyanarachchi, Sandya;Davuluri, Ramana V.;Nagy, Rebecca;de la Chapelle, Albert

A genome-wide association study of papillary thyroid carcinoma (PTC) pinpointed two independent SNPs (rs944289 and rs965513) located in regions containing no annotated genes (14q13.3 and 9q22.33, respectively). Here, we describe a unique, long, intergenic, noncoding RNA gene (lincRNA) named Papillary Thyroid Carcinoma Susceptibility Candidate 3 (PTCSC3) located 3.2 kb downstream of rs944289 at 14q.13.3 and the expression of which is strictly thyroid specific. By quantitative PCR, PTCSC3 expression was strongly down-regulated (P = 2.84 × 10−14) in thyroid tumor tissue of 46 PTC patients and the risk allele (T) was associated with the strongest suppression (genotype [TT] (n = 21) vs. [CT] (n = 19), P = 0.004). In adjacent unaffected thyroid tissue, the genotype [TT] was associated with up-regulation of PTCSC3 ([TT] (n = 21) vs. [CT] (n = 19), P = 0.034). The SNP rs944289 was located in a binding site for the CCAAT/enhancer binding proteins (C/EBP) α and β. The risk allele destroyed ...

Mots clés : Thyroïde; Etiologie (Facteurs endogènes)

Menée sur une cohorte de 234 494 femmes, cette étude prospective suédoise évalue l'association entre les niveaux de différents composants lipidiques et le risque de cancer du sein (6 105 cas) ou de l'ovaire (808 cas)

Lipid Profiles and Risk of Breast and Ovarian Cancer in the Swedish AMORIS Study
• Cancer Epidemiology Biomarkers & Prevention, sous presse, 2012 (résumé)

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Menée sur une cohorte de 234 494 femmes, cette étude prospective suédoise évalue l'association entre les niveaux de différents composants lipidiques et le risque de cancer du sein (6 105 cas) ou de l'ovaire (808 cas)

“Lipid Profiles and Risk of Breast and Ovarian Cancer in the Swedish AMORIS Study”

• Melvin, Jennifer C.;Seth, Divya;Holmberg, Lars;Garmo, Hans;Hammar, Niklas;Jungner, Ingmar;Walldius, Goran;Lambe, Mats;Wigertz, Annette;Van Hemelrijck, Mieke

Background: Obesity is a risk factor for breast (BCa) and ovarian cancer (OCa); the mechanisms of action are not completely understood. Perturbed lipid metabolism often accompanies obesity; we therefore ascertained the associations between lipid components and BCa and OCa risk in a prospective cohort study. Methods: 234,494 women with baseline measurements of triglycerides (TG) and total cholesterol(TC) and glucose were selected from the AMORIS database. 27,394 had measurements of HDL,LDL, apolipoprotein (Apo) B and A-I. Associations between quartiles and dichotomized values of lipid components and BCa and OCa risk were analysed using Cox proportional hazard models. Results: We identified 6,105 women diagnosed with BCa and 808 women diagnosed with OCa. A weak trend was observed between TG and BCa (HR: 1.01 (CI95% 0.94-1.09), 0.93 (0.86-1.00) 0.91 (0.84-0.99) 2nd 3rd and 4th quartiles; P = 0.01). No other associations between lipid components and risk of BCa or OCa showed statistical ...

Mots clés : Sein; Etiologie (Facteurs endogènes)

Cette étude évalue le risque de cancer du foie chez des anciens combattants américains atteints d'une cirrhose diagnostiquée entre 1969 et 1996 (103 257 participants, 788 cas)

Risk of liver cancer among US male veterans with cirrhosis, 1969-1996
• British Journal of Cancer, sous presse, 2012 (résumé)

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Cette étude évalue le risque de cancer du foie chez des anciens combattants américains atteints d'une cirrhose diagnostiquée entre 1969 et 1996 (103 257 participants, 788 cas)

“Risk of liver cancer among US male veterans with cirrhosis, 1969-1996”

• Persson, E. C.;Quraishi, S. M.;Welzel, T. M.;Carreon, J. D.;Gridley, G.;Graubard, B. I.;McGlynn, K. A.

Background : Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected. Methods : Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate. Results : Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR=37.59, 95% CI: ...

Mots clés : Foie; Etiologie (Facteurs endogènes)

Menée en Chine, cette étude (206 cas et 350 témoins) évalue l'association entre les niveaux d'insuline et de la protéine IGFBP-rP1 et le risque de cancer de l'endomètre

Serum insulin-like, growth factor binding protein-related protein 1 (IGFBP-rP1) and endometrial cancer risk in Chinese women
• International Journal of Cancer, sous presse, 2012 (résumé)

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Menée en Chine, cette étude (206 cas et 350 témoins) évalue l'association entre les niveaux d'insuline et de la protéine IGFBP-rP1 et le risque de cancer de l'endomètre

“Serum insulin-like, growth factor binding protein-related protein 1 (IGFBP-rP1) and endometrial cancer risk in Chinese women”

• Zhan, Yan;Wang, Jiamin;Ma, Yu;Liu, Zhiwei;Xu, Haiming;Lu, Shiming;Lu, Bingjian

Hyperinsulinemia and the metabolic syndrome confer increased risks of endometrial carcinoma. The roles of insulin, and, insulin-like growth factor-binding proteins (IGFBPs) in the etiology of endometrial carcinoma, remain unclear. We recruited 206 patients with endometrial carcinoma and 350 healthy women to a case–control study of fasting insulin and IGFBP-related protein 1 (IGFBP-rP1) in a Chinese tertiary centre. Patients with endometrial carcinoma had higher insulin concentrations (14.8 ± 16.7 vs. 8.1 ± 9.4 μU/mL; p < 0.001) and lower IGFBP-rP1 levels (17.5 ± 17.2 vs. 22.4 ± 22.8 μg/L; p = 0.018) than controls. High insulin and IGFBP-rP1 levels were both positively and negatively associated with endometrial cancer (odds ratio for the highest tertile versus the lowest tertile: insulin: 4.11; 95% CI = 2.61–6.47; IGFBP-rP1: 0.38; 95% CI = 0.24–0.60). Logistic regression analysis confirmed the associations between endometrial carcinoma and fasting insulin or IGFBP-rP1 after ...

Mots clés : Corps de l'utérus; Etiologie (Facteurs endogènes)

A partir des données de deux études cas-témoins portant au total sur 2 309 patients atteints d'un cancer du côlon ou du rectum et sur 2 915 témoins, cette étude américaine évalue l'association entre des polymorphismes à simple nucléotide de gènes codant pour des sélénoprotéines et le risque de développer la maladie

Genetic Variation in Selenoprotein Genes, Lifestyle, and Risk of Colon and Rectal Cancer
• PLoS ONE, Vol. 7 (5), pp. e37312, 2012 (article en libre accès)

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A partir des données de deux études cas-témoins portant au total sur 2 309 patients atteints d'un cancer du côlon ou du rectum et sur 2 915 témoins, cette étude américaine évalue l'association entre des polymorphismes à simple nucléotide de gènes codant pour des sélénoprotéines et le risque de développer la maladie

“Genetic Variation in Selenoprotein Genes, Lifestyle, and Risk of Colon and Rectal Cancer”

• Slattery, Martha L.;Lundgreen, Abbie;Welbourn, Bill;Corcoran, Christopher;Wolff, Roger K.

Background : Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. Methods : We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH), SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. Results : After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208). Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT ...

Mots clés : Colon-rectum; Etiologie (Facteurs endogènes)

Menée en Chine, cette étude (1 019 cas et 800 témoins) évalue l'association entre des polymorphismes du gène PARP-1 et le risque de carcinome du col de l'utérus

PARP-1 Val762Ala Polymorphism Is Associated with Risk of Cervical Carcinoma
• PLoS ONE, Vol. 7 (5), pp. e37446, 2012 (résumé)

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Menée en Chine, cette étude (1 019 cas et 800 témoins) évalue l'association entre des polymorphismes du gène PARP-1 et le risque de carcinome du col de l'utérus

“PARP-1 Val762Ala Polymorphism Is Associated with Risk of Cervical Carcinoma”

• Ye, Feng;Cheng, Qi;Hu, Yuting;Zhang, Jing;Chen, Huaizeng

PARP-1 is a nuclear enzyme that plays an important role in DNA repair, recombination, proliferation and the genome stability. The PARP-1 Val762Ala polymorphism has been associated with increased risk of developing cancers of the prostate, esophagus and lung. The aim of this study was to determine whether the PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma. MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with cervical carcinoma, 480 women with CIN and 800 controls. The genotyping method was confirmed by the DNA sequencing analysis. The PARP-1 Val762Ala polymorphism was not associated with the risk of CIN. However, women carrying the PARP-1 Ala762Ala genotype were significantly susceptible to cervical carcinoma (OR: 2.70, 95% CI: 1.47–3.70), and the similar results were also found in squamous cell carcinoma (OR: 2.56, 95% CI: 1.47–3.70). In HPV positive population, the PARP-1 Ala762Ala genotype was also associated with ...

Mots clés : Col de l'utérus; Etiologie (Facteurs endogènes)

Menée sur 2 440 participants (1 351 d'ascendance européenne, 1 088 d'ascendance africaine), cette étude de séquençage des exons de 15 585 gènes codant pour des protéines analyse l'évolution des variants rares et évalue les tailles d'échantillons de population nécessaires pour mettre en évidence des associations entre variants rares et maladies humaines

Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes
• Science, sous presse, 2012 (résumé)

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Menée sur 2 440 participants (1 351 d'ascendance européenne, 1 088 d'ascendance africaine), cette étude de séquençage des exons de 15 585 gènes codant pour des protéines analyse l'évolution des variants rares et évalue les tailles d'échantillons de population nécessaires pour mettre en évidence des associations entre variants rares et maladies humaines

“Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes”

• Tennessen, Jacob A.;Bigham, Abigail W.;O’Connor, Timothy D.;Fu, Wenqing;Kenny, Eimear E.;Gravel, Simon;McGee, Sean;Do, Ron;Liu, Xiaoming;Jun, Goo;Kang, Hyun Min;Jordan, Daniel;Leal, Suzanne M.;Gabriel, Stacey;Rieder, Mark J.;Abecasis, Goncalo;Altshuler, David;Nickerson, Deborah A.;Boerwinkle, Eric;Sunyaev, Shamil;Bustamante, Carlos D.;Bamshad, Michael J.;Akey, Joshua M.;Broad GO;Seattle GO;on behalf of the NHLBI Exome Sequencing Project

As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111x in 2,440 individuals of European (n = 1,351) and African (n = 1,088) ancestry. We identified >500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency < 0.5%), novel (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carries were predicted to impact protein function of ~313 genes per genome, and ~95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits.

Mots clés : Cancer (général); Etiologie (Facteurs endogènes)

Menée sur 14 002 participants, cette étude de séquençage met en évidence le grand nombre de variants rares dans 202 gènes codant pour des cibles thérapeutiques

An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People
• Science, sous presse, 2012 (résumé)

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Menée sur 14 002 participants, cette étude de séquençage met en évidence le grand nombre de variants rares dans 202 gènes codant pour des cibles thérapeutiques

“An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People”

• Nelson, Matthew R.;Wegmann, Daniel;Ehm, Margaret G.;Kessner, Darren;St. Jean, Pamela;Verzilli, Claudio;Shen, Judong;Tang, Zhengzheng;Bacanu, Silviu-Alin;Fraser, Dana;Warren, Liling;Aponte, Jennifer;Zawistowski, Matthew;Liu, Xiao;Zhang, Hao;Zhang, Yong;Li, Jun;Li, Yun;Li, Li;Woollard, Peter;Topp, Simon;Hall, Matthew D.;Nangle, Keith;Wang, Jun;Abecasis, Gonçalo;Cardon, Lon R.;Zöllner, Sebastian;Whittaker, John C.;Chissoe, Stephanie L.;Novembre, John;Mooser, Vincent

Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (one every 17 bases) and geographically localized, such that even with large sample sizes, rare variant catalogs will be largely incomplete. We used the observed patterns of variation to estimate population growth parameters, the proportion of variants in a given frequency class that are putatively deleterious, and mutation rates for each gene. Overall, we conclude that, due to rapid population growth and weak purifying selection, human populations harbor an abundance of rare variants, many of which are deleterious and have relevance to understanding disease risk.

Mots clés : Cancer (général); Etiologie (Facteurs endogènes)

Interactions gènes-environnement

Couplée à la cohorte européenne EPIC, cette étude prospective incluant 4 607 participantes évalue l'association entre l'adiposité, l'utilisation d'un traitement hormonal substitutif de la ménopause et le risque de cancer du sein, en fonction de l'âge et du statut du récepteur hormonal

Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study
• Breast Cancer Research, Vol. 14 (3), pp. R76, 2012 (résumé)

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Couplée à la cohorte européenne EPIC, cette étude prospective incluant 4 607 participantes évalue l'association entre l'adiposité, l'utilisation d'un traitement hormonal substitutif de la ménopause et le risque de cancer du sein, en fonction de l'âge et du statut du récepteur hormonal

“Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study”

• Ritte, Rebecca;Lukanova, Annekatrin;Berrino, Franco;Dossus, Laure;Tjonneland, Anne;Olsen, Anja;Overvad, Thure;Overvad, Kim;Clavel-Chapelon, Francoise;Fournier, Agnes;Fagherazzi, Guy;Rohrmann, Sabine;Teucher, Birgit;Boeing, Heiner;Aleksandrova, Krasimira;Trichopoulou, Antonia;Lagiou, Pagona;Trichopoulos, Dimitrios;Palli, Domenico;Sieri, Sabina;Panico, Salvatore;Tumino, Rosario;Vineis, Paolo;Ramon Quiros, Jose;Buckland, Genevieve;Sanchez, Maria-Jose;Amiano, Pilar;Chirlaque, Maria-Dolores;Ardanaz, Eva;Sund, Malin

INTRODUCTION:Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use.METHODS:Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen receptor (ER)-progesterone receptor (PR)- (n=1,021) and ER+PR+ (n=3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed.RESULTS:For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (3rd versus 1st tertile HR=1.47[1.01-2.15]) was observed. BMI was inversely associated with ER+PR+ tumors among ...

Mots clés : Sein; Etiologie (Interactions gènes-environnement)

A partir des données de l'étude "California Collaborative Case-Control Study of Prostate Cancer" (1 460 cas et 760 témoins), cette étude évalue l'association entre des polymorphismes de 9 enzymes du métabolisme, une consommation alimentaire de poisson, et le risque de cancer de la prostate

Polymorphisms in carcinogen metabolism enzymes, fish intake, and risk of prostate cancer
• Carcinogenesis, sous presse, 2012 (résumé)

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A partir des données de l'étude "California Collaborative Case-Control Study of Prostate Cancer" (1 460 cas et 760 témoins), cette étude évalue l'association entre des polymorphismes de 9 enzymes du métabolisme, une consommation alimentaire de poisson, et le risque de cancer de la prostate

“Polymorphisms in carcinogen metabolism enzymes, fish intake, and risk of prostate cancer”

• Catsburg, Chelsea;Joshi, Amit;Corral, Roman;Lewinger, Juan-Pablo;Koo, Jocelyn;John, Esther;Ingles, Sue;Stern, Mariana

Cooking fish at high temperature can produce potent carcinogens such as heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). The effects of these carcinogens may undergo modification by the enzymes responsible for their detoxification and/or activation. In this study, we investigated genetic polymorphisms in nine carcinogen metabolism enzymes and their modifying effects on the association between white or dark fish consumption and prostate cancer (PCA) risk. We genotyped 497 localized and 936 advanced PCA cases and 760 controls from the California Collaborative Case-Control Study of Prostate Cancer. Three polymorphisms, EPHX1 Tyr113His, CYP1B1 Leu432Val and GSTT1 null/present, were associated with localized PCA risk. The PTGS2 765 G/C polymorphism modified the association between white fish consumption and advanced PCA risk (interaction p = 0.002), with high white fish consumption being positively associated with risk only among carriers of the C allele. This effect ...

Mots clés : Prostate; Etiologie (Interactions gènes-environnement)

Menée au Danemark, cette étude de cohorte incluant 57 053 participants et 378 cas de cancer évalue l'association entre des polymorphismes du gène IL10, une consommation alimentaire de fibres et le risque de cancer colorectal

Interaction between interleukin-10 (IL-10) polymorphisms and dietary fibre in relation to risk of colorectal cancer in a Danish case-cohort study
• BMC Cancer, Vol. 12 (1), pp. 183, 2012 (résumé)

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Menée au Danemark, cette étude de cohorte incluant 57 053 participants et 378 cas de cancer évalue l'association entre des polymorphismes du gène IL10, une consommation alimentaire de fibres et le risque de cancer colorectal

“Interaction between interleukin-10 (IL-10) polymorphisms and dietary fibre in relation to risk of colorectal cancer in a Danish case-cohort study”

• Andersen, Vibeke;Egebjerg, Rikke;Tjonneland, Anne;Vogel, Ulla

BACKGROUND:More than 50% of the colorectal cancer (CRC) etiology has been attributed to diet. Established or suspected dietary factors modifying risk of CRC are red meat, cereals, fish, and fibre. Diet and lifestyle may be linked to cancer through inflammation. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. We wanted to test if dietary factors and IL10 polymorphisms interact in relation to colorectal carcinogenesis.METHODS:The functional IL10 polymorphism C-592A (rs1800872) and the marker rs3024505 were assessed in relation to diet and lifestyle in a nested case-cohort study of 378 CRC cases and 775 randomly selected participants from a prospective study of 57,053 persons. Genotyping data on the IL10 polymorphism C-592A, smoking and non-steroidal anti-inflammatory drugs (NSAID) was retrieved from Vogel et al (Mutat Res, 2007; 624:88). Incidence rate ratios (IRR) and 95% Confidence Interval (95% CI) were calculated.RESULTS:No associations were found between the IL10 rs3024505 ...