Delahaye-Sourdeix Manon, Anantharaman Devasena, Timofeeva Maria N, Gaborieau Valérie, Chabrier Amélie, Vallée Maxime P, Lagiou Pagona, Holcátová Ivana, Richiardi Lorenzo, Kjaerheim Kristina, Agudo Antonio, Castellsagué Xavier, Macfarlane Tatiana V, Barzan Luigi, Canova Cristina, Thakker Nalin S, Conway David I, Znaor Ariana, Healy Claire M, Ahrens Wolfgang, Zaridze David, Szeszenia-Dabrowska Neonilia, Lissowska Jolanta, Fabianova Eleonora, Mates Ioan Nicolae, Bencko Vladimir, Foretova Lenka, Janout Vladimir, Curado Maria Paula, Koifman Sergio, Menezes Ana, Wünsch-Filho Victor, Eluf-Neto José, Boffetta Paolo, Fernández Garrote Leticia, Polesel Jerry, Lener Marcin, Jaworowska Ewa, Lubiński Jan, Boccia Stefania, Rajkumar Thangarajan, Samant Tanuja A, Mahimkar Manoj B, Matsuo Keitaro, Franceschi Silvia, Byrnes Graham, Brennan Paul, McKay James D
: Genetic Cancer Susceptibility Group (MDS, AC, MPV, JDM), Genetic Epidemiology Group (DA, MNT, VG, PBr), Infections and Cancer Epidemiology Group (SF), and Biostatistics Group (GB), International Agency for Research on Cancer, Lyon, France; Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council, Human Genetics Unit, Edinburgh, UK (MNT); Department of Hygiene, Epidemiology and Medical Statistics, University of Athens School of Medicine, Athens, Greece (PL); Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic (IH, VB); University of Turin, Department of Medical Sciences, Unit of Cancer Epidemiology, Turin, Italy (LR); Cancer Registry of Norway, Oslo, Norway (KK); Catalan Institute of Oncology-ICO, IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain (AA, XC); CIBER Epidemiología y Salud Pública, Spain (XC); School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK (TVM); General Hospital of Pordenone, Pordenone, Italy (LB); Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy (CC); MRC-HPA Centre for Environment and Health, Respiratory Epidemiology and Public Health, National Heart and Lung Institute, Imperial College, London, UK (CC); University of Manchester, School of Dentistry, Manchester, UK (NST); University of Glasgow Dental School, Glasgow, Scotland, UK (DIC); Croatian National Cancer Registry, Croatian National Institute of Public Health, Zagreb, Croatia (AZ); Trinity College School of Dental Science, Dublin, Ireland (CMH); Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany (WA); Faculty of Mathematics and Computer Science, University of Bremen, Bremen, Germany (WA); Institute of Carcinogenesis, Cancer Research Centre, Moscow, Russian Federation (DZ); Department of Epidemiology, Institute of Occupational Medicine, Lodz, Poland (NSD); Department of Ca
J Natl Cancer Inst. 2015 Apr 2;107(5). doi: 10.1093/jnci/djv037. Print 2015 May.
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.
有害的BRCA2基因变异会显著增加患乳腺癌的风险。一种罕见的截短型BRCA2基因变异，rs11571833（K3326X），与肺鳞状细胞癌风险增加2.5倍相关，但仅使乳腺癌风险适度增加26%。我们通过多变量无条件逻辑回归分析了BRCA2单核苷酸多态性rs11571833与上消化道（UADT）癌症风险之间的关联，该回归按性别以及研究和国家的组合进行了调整，纳入了来自9项不同研究的5942例UADT鳞状细胞癌病例患者和8086例对照患者。所有统计检验均为双侧检验。rs11571833与UADT癌症相关（比值比 = 2.53，95%置信区间 = 1.89至3.38，P = 3×10⁻¹⁰），在欧洲、拉丁美洲和印度人群中存在，但在日本人群中极为罕见。与从不吸烟者相比，该关联在当前或既往吸烟者中似乎更明显（P异质性 = 0.026）。截短型BRCA2变异与UADT癌症风险之间的有力关联表明，针对BRCA2突变的治疗策略可能值得在上消化道肿瘤中进一步研究。
