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Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

HASHIBE, Mia; BRENNAN, Paul; CHUANG, Shu-Chun; BOCCIA, Stefania; CASTELLSAGUE, Xavier; CHEN, Chu; CURADO, Maria Paula; MASO, Luigino Dal; DAUDT, Alexander W.; FABIANOVA, Eleonora; FERNANDEZ, Leticia; WÜNSCH-FILHO, Victor; FRANCESCHI, Silvia; HAYES, Richa
Fonte: AMER ASSOC CANCER RESEARCH Publicador: AMER ASSOC CANCER RESEARCH
Tipo: Artigo de Revista Científica
ENG
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Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases < 45 years, 73% for cases > 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However...

Involuntary smoking and head and neck cancer risk: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium

LEE, Yuan-Chin Amy; BOFFETTA, Paolo; STURGIS, Erich M.; WEI, Qingyi; ZHANG, Zuo-Feng; MUSCAT, Joshua; LAZARUS, Philip; MATOS, Elena; HAYES, Richard B.; WINN, Deborah M.; ZARIDZE, David; WÜNSCH-FILHO, Victor; ELUF-NETO, Jose; KOIFMAN, Sergio; MATES, Dana;
Fonte: AMER ASSOC CANCER RESEARCH Publicador: AMER ASSOC CANCER RESEARCH
Tipo: Artigo de Revista Científica
ENG
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Although active tobacco smoking has been identified as a major risk factor for head and neck cancer, involuntary smoking has not been adequately evaluated because of the relatively low statistical power in previous studies. We took advantage of data pooled in the International Head and Neck Cancer Epidemiology Consortium to evaluate the role of involuntary smoking in head and neck carcinogenesis. Involuntary smoking exposure data were pooled across six case-control studies in Central Europe, Latin America, and the United States. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542 cases and 2,197 controls who reported never using tobacco, and the heterogeneity among the study-specific ORs was assessed. In addition, stratified analyses were done by subsite. No effect of ever involuntary smoking exposure either at home or at work was observed for head and neck cancer overall. However, long duration of involuntary smoking exposure at home and at work was associated with an increased risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; P(trend) <0-01; OR for >15 years at work, 1.55; 95% CI, 1.04-2.30; P(trend) = 0.13). The effect of duration of involuntary smoking exposure at home was stronger for pharyngeal and laryngeal cancers than for other subsites. An association between involuntary smoking exposure and the risk of head and neck cancer...

East meets West: ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians

Zhou, Wei; Christiani, David C.
Fonte: Sun Yat-sen University Cancer Center Publicador: Sun Yat-sen University Cancer Center
Tipo: Artigo de Revista Científica
EN_US
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Lung cancer is the leading cause of cancer death worldwide, with large variation of the incidence and mortality across regions. Although the mortality of lung cancer has been decreasing, or steady in the US, it has been increasing in Asia for the past two decades. Smoking is the leading cause of lung cancer, and other risk factors such as indoor coal burning, cooking fumes, and infections may play important roles in the development of lung cancer among Asian never smoking women. The median age of diagnosis in Asian patients with lung cancer is generally younger than Caucasian patients, particularly among never-smokers. Asians and Caucasians may have different genetic susceptibilities to lung cancer, as evidenced from candidate polymorphisms and genome-wide association studies. Recent epidemiologic studies and clinical trials have shown consistently that Asian ethnicity is a favorable prognostic factor for overall survival in non-small cell lung cancer (NSCLC), independent of smoking status. Compared with Caucasian patients with NSCLC, East Asian patients have a much higher prevalence of epidermal growth factor receptor (EGFR) mutation (approximately 30% vs. 7%, predominantly among patients with adenocarcinoma and never-smokers), a lower prevalence of K-Ras mutation (less than 10% vs. 18%...

Epidemiologic studies of particulate matter and lung cancer

Li, Yin-Ge; Gao, Xiang
Fonte: Sun Yat-sen University Cancer Center Publicador: Sun Yat-sen University Cancer Center
Tipo: Artigo de Revista Científica
EN_US
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Particulate matter (PM) plays an important role in air pollution, especially in China. European and American researchers conducted several cohort-based studies to examine the potential relationship between PM and lung cancer and found a positive association between PM and lung cancer mortality. In contrast, the results regarding PM and lung cancer risk remain inconsistent. Most of the previous studies had limitations such as misclassification of PM exposure and residual confounders, diminishing the impact of their findings. In addition, prospective studies on this topic are very limited in Chinese populations. This is an important problem because China has one of the highest concentrations of PM in the world and has had an increased mortality risk due to lung cancer. In this context, more prospective studies in Chinese populations are warranted to investigate the relationship between PM and lung cancer.

Unemployment and prostate cancer mortality in the OECD, 1990–2009

Maruthappu, Mahiben; Watkins, Johnathan; Taylor, Abigail; Williams, Callum; Ali, Raghib; Zeltner, Thomas; Atun, Rifat
Fonte: Cancer Intelligence Publicador: Cancer Intelligence
Tipo: Artigo de Revista Científica
EN_US
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The global economic downturn has been associated with increased unemployment in many countries. Insights into the impact of unemployment on specific health conditions remain limited. We determined the association between unemployment and prostate cancer mortality in members of the Organisation for Economic Co-operation and Development (OECD). We used multivariate regression analysis to assess the association between changes in unemployment and prostate cancer mortality in OECD member states between 1990 and 2009. Country-specific differences in healthcare infrastructure, population structure, and population size were controlled for and lag analyses conducted. Several robustness checks were also performed. Time trend analyses were used to predict the number of excess deaths from prostate cancer following the 2008 global recession. Between 1990 and 2009, a 1% rise in unemployment was associated with an increase in prostate cancer mortality. Lag analysis showed a continued increase in mortality years after unemployment rises. The association between unemployment and prostate cancer mortality remained significant in robustness checks with 46 controls. Eight of the 21 OECD countries for which a time trend analysis was conducted, exhibited an estimated excess of prostate cancer deaths in at least one of 2008...

Using real-time impedance-based assays to monitor the effects of fibroblast-derived media on the adhesion, proliferation, migration and invasion of colon cancer cells

Dowling, Catríona M; Herranz Ors, Carmen; Kiely, Patrick A
Fonte: Portland Press Publicador: Portland Press
Tipo: info:eu-repo/semantics/article; all_ul_research; ul_published_reviewed
ENG
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peer-reviewed; Increasing our knowledge of the mechanisms regulating cell proliferation, migration and invasion are central to understanding tumour progression and metastasis. The local tumour microenvironment contributes to the transformed phenotype in cancer by providing specific environmental cues that alter the cells behaviour and promotes metastasis. Fibroblasts have a strong association with cancer and in recent times there has been some emphasis in designing novel therapeutic strategies that alter fibroblast behaviour in the tumour microenvironment. Fibroblasts produce growth factors, chemokines and many of the proteins laid down in the ECM (extracellular matrix) that promote angiogenesis, inflammation and tumour progression. In this study, we use a label-free RTCA (real-time cell analysis) platform (xCELLigence) to investigate how media derived from human fibroblasts alters cancer cell behaviour. We used a series of complimentary and novel experimental approaches to show HCT116 cells adhere, proliferate and migrate significantly faster in the presence of media from human fibroblasts. As well as this, we used the xCELLigence CIMplates system to show that HCT116 cells invade matrigel layers aggressively when migrating towards media derived from human fibroblasts. These data strongly suggest that fibroblasts have the ability to increase the migratory and invasive properties of HCT116 cells. This is the first study that provides real-time data on fibroblast-mediated migration and invasion kinetics of colon cancer cells.

Breast screening and breast cancer survival in Aboriginal and Torres Strait Islander women of Australia

Roder, D.; Webster, F.; Zorbas, H.; Sinclair, S.; Aitken, J.; Culjak, G.; Elston, J.; Epping, Y.; Farrugia, H.; Grayson, N.; Guthridge, S.; Halliday, L.; Muller, J.; Pridmore, V.; Threlfall, T.; Tyzack, C.; Venn, A.; Ward, G.; Williamson, L.; Wylie, L.
Fonte: Asian Pacific Organization for Cancer Prevention Publicador: Asian Pacific Organization for Cancer Prevention
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
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Aboriginal and Torres Strait Islander people comprise about 2.5% of the Australian population. Cancer registry data indicate that their breast cancer survivals are lower than for other women but the completeness and accuracy of Indigenous descriptors on registries are uncertain. We followed women receiving mammography screening in BreastScreen to determine differences in screening experiences and survivals from breast cancer by Aboriginal and Torres Strait Islander status, as recorded by BreastScreen. This status is self-reported and used in BreastScreen accreditation, and is considered to be more accurate. The study included breast cancers diagnosed during the period of screening and after leaving the screening program. Design: Least square regression models were used to compare screening experiences and outcomes adjusted for age, geographic remoteness, socio-economic disadvantage, screening period and round during 1996-2005. Survival of breast cancer patients from all causes and from breast cancer specifically was compared for the 1991-2006 diagnostic period using linked cancer-registry data. Cox proportional hazards regression was used to adjust for socio-demographic differences, screening period, and where available, tumour size...

Polycystic ovary syndrome increases the risk of endometrial cancer in women aged less than 50 years: an Australian case–control study

Fearnley, E.J.; Marquart, L.; Spurdle, A.B.; Weinstein, P.; Webb, P.M.; Oehler, M.K.; Australian Ovarian Cancer Study Group; Australian National Endometrial Cancer Study Group
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
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Objective: Although polycystic ovary syndrome (PCOS) is commonly cited as a risk factor for endometrial cancer, supporting epidemiological evidence is currently very limited. Our aim was to assess the associations between PCOS, PCOS symptoms, and risk of endometrial cancer in women aged less than 50 years. Methods: Data came from a national population-based case–control study in Australia. Cases with newly diagnosed histologically confirmed endometrial cancer were identified through treatment clinics and cancer registries Australia wide. Controls were randomly selected from the national electoral roll. Women were interviewed about their reproductive and medical history, including self-reported PCOS, and lifestyle. Current analyses were restricted to women aged under 50 (156 cases, 398 controls). We estimated odds ratios (OR) using logistic regression to adjust for confounding factors. Results: Women with PCOS had a fourfold increased risk of endometrial cancer compared to women without PCOS (OR 4.0, 95% CI 1.7–9.3). This association was attenuated when additionally adjusted for body mass index (OR 2.2, 95% CI 0.9–5.7). Risk was slightly greater when restricted to Type I cancers. PCOS symptoms including hirsutism and very irregular periods were significantly associated with endometrial cancer risk. Conclusions: These data extend existing findings...

What sort of follow-up services would Australian breast cancer survivors prefer if we could no longer offer long-term specialist-based care? A discrete choice experiment

Bessen, T.; Chen, G.; Street, J.; Eliott, J.; Karnon, J.; Keefe, D.; Ratcliffe, J.
Fonte: Cancer Research UK Publicador: Cancer Research UK
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
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Background: Early diagnosis and improved treatment outcomes have increased breast cancer survival rates that, in turn, have led to increased numbers of women undergoing follow-up after completion of primary treatment. The current workload growth is unsustainable for breast cancer specialists who also provide care for women newly diagnosed or with a recurrence. Appropriate and acceptable follow-up care is important; yet, currently we know little about patient preferences. The aim of this study was to explore the preferences of Australian breast cancer survivors for alternative modes of delivery of follow-up services. Methods: A self-administered questionnaire (online or paper) was developed. The questionnaire contained a discrete choice experiment (DCE) designed to explore patient preferences with respect to provider, location, frequency and method of delivery of routine follow-up care in years 3, 4 and 5 after diagnosis, as well as the perceived value of ‘drop-in’ clinics providing additional support. Participants were recruited throughout Australia over a 6-month period from May to October 2012. Preference scores and choice probabilities were used to rank the top 10 most preferred follow-up scenarios for respondents. Results: A total of 836 women participated in the study...

Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer

Merritt, M.; Green, A.C.; Nagle, C.M.; Webb, P.M.; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group; Dodd, T.; Pittman, K.; Miller, J.
Fonte: Wiley-Liss Publicador: Wiley-Liss
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
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Abstract not available; Melissa A. Merritt, Adèle C. Green, Christina M. Nagle, Penelope M. Webb, Australian Cancer Study (Ovarian Cancer) and Australian Ovarian Cancer Study Group; T Dodd, K Pittman and J Miller are members of The Australian Ovarian Cancer Study Group

Glycemic index, glycemic load and endometrial cancer risk: results from the Australian National Endometrial Cancer study and an updated systematic review and meta-analysis

Nagle, C.M.; Olsen, C.M.; Ibiebele, T.I.; Spurdle, A.B.; Webb, P.M.; Australian National Endometrial Cancer Study Group; Australian Ovarian Cancer Study Group
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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Purpose: The relationship between habitual consumption of foods with a high glycemic index (GI) and/or a diet with a high glycemic load (GL) and risk of endometrial cancer is uncertain, and relatively few studies have investigated these associations. The objectives of this study were to examine the association between GI/GL and risk of endometrial cancer using data from an Australian population-based case–control study and systematically review all the available evidence to quantify the magnitude of the association using meta-analysis. Methods: The case–control study included 1,290 women aged 18–79 years with newly diagnosed, histologically confirmed endometrial cancer and 1,436 population controls. Controls were selected to match the expected Australian state of residence and age distribution (in 5-year bands) of cases. For the systematic review, relevant studies were identified by searching PubMed and Embase databases through to July 2011. Random-effects models were used to calculate the summary risk estimates, overall and dose–response. Results: In our case–control study, we observed a modest positive association between high dietary GI (OR 1.43, 95 % CI 1.11–1.83) and risk of endometrial cancer, but no association with high dietary GL (OR 1.15...

The global burden of cancer 2013

Global Burden of Disease Cancer Collaboration
Fonte: JAMA Publicador: JAMA
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
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IMPORTANCE: Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. EVIDENCE REVIEW: The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. FINDINGS: In 2013 there were 14.9 million incident cancer cases...

Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer

Yang, Lifeng; Moss, Tyler; Mangala, Lingegowda S.; Marini, Juan; Zhao, Hongyun; Wahlig, Stephen; Armaiz-Pena, Guillermo; Jiang, Dahai; Achreja, Abhinav; Win, Julia; Roopaimoole, Rajesha; Rodriguez-Aguayo, Cristian; Mercado-Uribe, Imelda; Lopez-Berestein,
Fonte: Universidade Rice Publicador: Universidade Rice
Tipo: Journal article; Text; publisher version
ENG
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Glutamine can play a critical role in cellular growth in multiple cancers. Glutamine‐addicted cancer cells are dependent on glutamine for viability, and their metabolism is reprogrammed for glutamine utilization through the tricarboxylic acid (TCA) cycle. Here, we have uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we found that low‐invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high‐invasive OVCA cells are markedly glutamine dependent. Consistent with our findings, OVCA patients’ microarray data suggest that glutaminolysis correlates with poor survival. Notably, the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis. Significantly, we found that glutamine regulates the activation of STAT3, a mediator of signaling pathways which regulates cancer hallmarks in invasive OVCA cells. Our findings suggest that a combined approach of targeting high‐invasive OVCA cells by blocking glutamine's entry into the TCA cycle, along with targeting low‐invasive OVCA cells by inhibiting glutamine synthesis and STAT3 may lead to potential therapeutic approaches for treating OVCAs.

Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

Olsen, C.M.; Nagle, C.M.; Whiteman, D.C.; Ness, R.; Pearce, C.L.; Pike, M.C.; Rossing, M.A.; Terry, K.L.; Wu, A.H.; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group; Risch, H.A.; Yu, H.; Doherty, J.A.; Chang-Claude, J.; Hein
Fonte: BioScientifica Publicador: BioScientifica
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13...

Season of birth and risk of endometrial cancer

Rowlands, I.J.; Weinstein, P.; Nagle, C.M.; Spurdle, A.B.; Webb, P.M.; Oehler, M.K.
Fonte: National Cancer Center, Korea Publicador: National Cancer Center, Korea
Tipo: Artigo de Revista Científica
Publicado em //2011 EN
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45.84%
OBJECTIVES: Season of birth has been associated with adult morbidity and mortality, but few epidemiological studies have examined whether season of birth contributes to the development of cancer. Using data from the Australian National Endometrial Cancer Study, a population-based case-control study of 1399 cases and 1539 controls, we examined the association between season of birth and risk of endometrial cancer. METHODS: Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between season of birth and endometrial cancer. Additional analyses were stratified by state of birth. RESULTS: Season of birth was not associated with endometrial cancer overall, but there was an increased risk among women born in summer in Tasmania, the most southerly state (OR = 4.46, 95% CI: 1.24-16.06) and non-significant increases in the other southern states. CONCLUSION: Further data are required to confirm these findings, however the observed associations may be due to the longer days and/or greater hours of sunshine in Australia's southerly states in summer, suppressing melatonin levels in summer-born infants and predisposing them to cancer in adulthood.; Ingrid J Rowlands, Philip Weinstein...

Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

Gao, B.; Russell, A.; Beesley, J.; Chen, X.Q.; Healey, S.; Henderson, M.; Wong, M.; Emmanuel, C.; Galletta, L.; Johnatty, S.E.; Bowtell, D.; Australian Ovarian Cancer Study Group; Haber, M.; Norris, M.; Harnett, P.; Chenevix-Trench, G.; Balleine, R.L.; De
Fonte: Nature Publishing Groups Publicador: Nature Publishing Groups
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
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45.84%
ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may underlie the association. Using cell-based models, we evaluated the correlations between ABCB1 expression, polymorphisms, transporter activity and paclitaxel sensitivity in ovarian cancer (n = 10) and lymphoblastoid (n = 19) cell lines. Close associations between ABCB1 expression, transporter function and paclitaxel sensitivity were found in lymphoblastoid cell lines, although we could not demonstrate an association with common SNPs. In ovarian cancer cell lines, ABCB1 expression was low and the association between expression and function was lost. These results suggest that ABCB1 related survival difference in ovarian cancer patients is more likely to be due to differential whole body paclitaxel clearance mediated by normal cells rather than a direct effect on cancer cells.; Bo Gao...

Patients with a high polygenic risk of breast cancer do not have an increased risk of radiotherapy toxicity; Overdiagnosis by polygenic risk

Dorling, Leila; Barnett, Gillian C.; Michailidou, Kyriaki; Coles, Charlotte E.; Burnet, Neil G.; Yarnold, John R.; Elliott, Rebecca M.; Dunning, Alison M.; Pharoah, Paul D. P.; West, Catharine M. L.
Fonte: American association for Cancer Research Publicador: American association for Cancer Research
Tipo: Article; accepted version
EN
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This is the author accepted manuscript. The final version is available from American association for Cancer Research via http://dx.doi.org/10.1158/1078-0432.CCR-15-1080; PURPOSE: This study aims to quantify the probability of overdiagnosis of prostate cancer by polygenic risk. METHODS: We calculated the polygenic risk score based on 66 known prostate cancer susceptibility variants for 17,012 men aged 50-69 years (9,404 men identified with prostate cancer and 7,608 with no cancer) derived from three UK-based ongoing studies. We derived the probabilities of overdiagnosis by quartiles of polygenic risk considering that the observed prevalence of screen-detected prostate cancer is a combination of underlying incidence, mean sojourn time (MST), test sensitivity, and overdiagnosis. RESULTS: Polygenic risk quartiles one to four had 9%, 18%, 25% and 48% of the cases respectively. For a PSA test sensitivity of 80% and MST of nine years, 43%, 30%, 25% and 19% of the prevalent screen-detected cancers in quartiles one to four, respectively, were likely to be overdiagnosed cancers. Overdiagnosis decreased with increasing polygenic risk, with 56% drop between the lowest and the highest polygenic risk quartiles. CONCLUSION: Targeting screening to men at higher polygenic risk could reduce the problem of overdiagnosis and lead to a better benefit to harm balance in screening for prostate cancer.; NP is Cancer Research UK Clinician Scientist Fellow. The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175)...

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

O'Mara, Tracy A.; Glubb, Dylan M.; Painter, Jodie N.; Cheng, Timothy; Dennis, Joe; Australian National Endometrial Cancer Study Group (ANECS); Attia, John; Holliday, Elizabeth G.; McEvoy, Mark; Scott, Rodney J.; Ashton, Katie; Proietto, Tony; Otton, Geoff
Fonte: Society for Endocrinology Publicador: Society for Endocrinology
Tipo: Article; published version
EN
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This is the final version of the article. It first appeared from the Society for Endocrinology via http://dx.doi.org/10.1530/ERC-15-0319; Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86?10?5), which was stronger for cancers of endometrioid subtype (P=3.76?10?6). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer...

CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer.

Thompson, Deborah J.; O?Mara, Tracy A.; Glubb, Dylan M.; Painter, Jodie N.; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M.; Australian National Endometrial Cancer Study Group (ANECS); Gorman, Maggie; Martin, Lynn; Hodgs
Fonte: Bioscientifica Publicador: Bioscientifica
Tipo: Article; published version
EN
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45.9%
This is the author accepted manuscript. The final version is available from Bioscientifica via http://dx.doi.org/10.1530/ERC-15-0386; Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol concentrations. We analysed 2,937 SNPs in 6,608 endometrial cancer cases and 37,925 controls and report the first genome wide significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10-11). SNP rs727479 was also among those most strongly associated with circulating estradiol concentrations in 2,767 post-menopausal controls (P=7.4x10- 8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11- 1.21) is compatible with that predicted by the observed effect on estradiol concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by estradiol. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.; Fine-mapping analysis was supported by NHMRC project grant [ID#1031333] to ABS...

Multistage carcinogenesis and lung cancer mortality in three cohorts

Hazelton, William D; Clements, Mark; Moolgavkar, Suresh
Fonte: American Association for Cancer Research Publicador: American Association for Cancer Research
Tipo: Artigo de Revista Científica
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Experimental evidence indicates that tobacco smoke acts both as an initiator and a promoter in lung carcinogenesis. We used the two-stage clonal expansion model incorporating the ideas of initiation, promotion, and malignant conversion to analyze lung cancer mortality in three large cohorts, the British Doctors' cohort and the two American Cancer Society cohorts, to determine how smoking habits influence age-specific lung cancer rates via these mechanisms. Likelihood ratio tests indicate that smoking-related promotion is the dominant model mechanism associated with lung cancer mortality in all cohorts. Smoking-related initiation is less important than promotion but interacts synergistically with it. Although no information on ex-smokers is available in these data, the model with estimated variables can be used to project risks among ex-smokers. These projected risks are in good agreement with the risk among ex-smokers derived from other studies. We present 10-year projected risks for current and former smokers adjusted for competing causes of mortality. The importance of smoking duration on lung cancer risk in these cohorts is a direct consequence of promotion. Intervention and treatment strategies should focus on promotion as the primary etiologic mechanism in lung carcinogenesis.