Delahaye-Sourdeix M.,International Agency for Research on Cancer IARC WHO |
Anantharaman D.,Genetic Epidemiology Group |
Timofeeva M.N.,Genetic Epidemiology Group |
Timofeeva M.N.,International Agency for Research on Cancer |
And 48 more authors.
Journal of the National Cancer Institute | Year: 2015
Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10-10) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het =. 026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors. © 2015 © The Author 2015. Published by Oxford University Press. Source
MacFarlane T.V.,University of Aberdeen |
MacFarlane G.J.,University of Aberdeen |
Oliver R.J.,University of Manchester |
Benhamou S.,French Institute of Health and Medical Research |
And 27 more authors.
Cancer Causes and Control | Year: 2010
Background: The incidence of cancers of the upper aerodigestive tract (UADT) is increasing throughout the world. To date the increases have been proportionally greatest among young people. Several reports have suggested that they often do not have a history of tobacco smoking or heavy alcohol consumption. Objective: To determine the contribution of lifestyle factors to the etiology of UADT cancers occurring in those aged less than 50 years. Methods: A case-control study was conducted in 10 European countries. Cases were cancers of the oral cavity and pharynx, larynx and esophagus, and hospital or population controls were age and sex matched. Results: There were 356 cases younger than 50 years and 419 controls. Risk was strongly related to current smoking [odds ratio (OR) 5.5 95%; confidence interval (CI) (3.3, 9.2)], and risk increased with number of pack-years smoked. Risk was also related to alcohol consumption for both current (OR 1.8; 0.97, 3.3) and past (OR 3.4; 1.6, 7.4) drinkers, and risk increased with number of drink-years. Persons frequently consuming fruits and vegetables were at significantly reduced risk. Conclusions: Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike. © 2010 Springer Science+Business Media B.V. Source
Park S.L.,University of California at Los Angeles |
Lee Y.-C.A.,University of California at Los Angeles |
Lee Y.-C.A.,University of Utah |
Marron M.,International Agency for Research on Cancer |
And 32 more authors.
International Journal of Cancer | Year: 2011
Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≤ 5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature. Copyright © 2010 UICC. Source
Anantharaman D.,International Agency for Research on Cancer |
Marron M.,University of Mainz |
Lagiou P.,National and Kapodistrian University of Athens |
Samoli E.,National and Kapodistrian University of Athens |
And 26 more authors.
Oral Oncology | Year: 2011
Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR = 85%) than oropharyngeal (PAR = 74%), esophageal (PAR = 67%) and oral cancer (PAR = 61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR = 84%) than southern (PAR = 72%) and western Europe (PAR = 67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe. © 2011 Elsevier Ltd. All rights reserved. Source
Delahaye-Sourdeix M.,International Agency for Research on Cancer IARC |
Oliver J.,International Agency for Research on Cancer IARC |
Timofeeva M.N.,International Agency for Research on Cancer IARC |
Timofeeva M.N.,University of Edinburgh |
And 51 more authors.
PLoS ONE | Year: 2015
Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95%CI: 1.04-1.15, p = 6x10-4). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10-3) and LUSC (p = 9x10-4) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10-48 and p = 3x10-29 in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors. © 2015 Delahaye-Sourdeix et al. Source