Obesity, inflammatory markers, and endometrial cancer risk: a prospective case-control study

被引：141

作者：

Dossus, Laure ^{[1
]}

Rinaldi, Sabina ^{[2
]}

Becker, Susen ^{[1
]}

Lukanova, Annekatrin ^{[1
,3
]}

Tjonneland, Anne ^{[4
]}

Olsen, Anja ^{[4
]}

Stegger, Jakob ^{[5
]}

Overvad, Kim ^{[5
,6
]}

Chabbert-Buffet, Nathalie ^{[7
,8
]}

Jimenez-Corona, Aida ^{[9
,10
]}

Clavel-Chapelon, Francoise ^{[9
]}

Rohrmann, Sabine ^{[1
]}

Teucher, Birgit ^{[1
]}

Boeing, Heiner ^{[11
]}

Schuetze, Madlen ^{[11
]}

Trichopoulou, Antonia ^{[12
,13
]}

Benetou, Vassiliki ^{[12
]}

Lagiou, Pagona ^{[12
]}

Palli, Domenico ^{[14
]}

Berrino, Franco ^{[15
]}

Panico, Salvatore ^{[16
]}

Tumino, Rosario ^{[17
,18
]}

Sacerdote, Carlotta ^{[19
,20
]}

Redondo, Maria-Luisa ^{[21
]}

Travier, Noemie ^{[22
]}

Sanchez, Maria-Jose ^{[23
,24
]}

Altzibar, Jone M. ^{[24
,25
]}

Chirlaque, Maria-Dolores ^{[24
,26
]}

Ardanaz, Eva ^{[24
,27
]}

Bueno-de-Mesquita, H. Bas ^{[28
]}

van Duijnhoven, Franzel J. B. ^{[28
]}

Onland-Moret, N. Charlotte ^{[29
]}

Peeters, Petra H. M. ^{[29
]}

Hallmans, Goran ^{[30
]}

Lundin, Eva ^{[31
]}

Khaw, Kay-Tee ^{[32
]}

Wareham, Nicholas ^{[33
]}

Allen, Naomi ^{[34
]}

Key, Tim J. ^{[34
]}

Slimani, Nadia ^{[2
]}

Hainaut, Pierre ^{[35
]}

Romaguera, Dora ^{[36
]}

Norat, Teresa ^{[36
]}

Riboli, Elio ^{[36
]}

Kaaks, Rudolf ^{[1
]}

机构：

[1] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, German Canc Res Ctr DKFZ, D-69120 Heidelberg, Germany

[2] Int Agcy Res Canc, Sect Nutr & Metab, F-69372 Lyon, France

[3] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA

[4] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark

[5] Aarhus Univ Hosp, Aalborg Hosp, Dept Cardiol, DK-9100 Aalborg, Denmark

[6] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, DK-8000 Aarhus, Denmark

[7] Hop Tenon, APHP, Dept Obstet & Gynaecol, F-75970 Paris, France

[8] UMPC, F-75970 Paris, France

[9] Paris S Univ, Inst Gustave Roussy, INSERM, Ctr Res Epidemiol & Populat Hlth, F-94805 Villejuif, France

[10] Natl Inst Publ Hlth, Cuernavaca 62100, Morelos, Mexico

[11] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, D-14558 Nuthetal, Germany

[12] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece

[13] Hellen Hlth Fdn, Athens 11527, Greece

[14] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, I-50139 Florence, Italy

[15] Ist Nazl Tumori, Epidemiol Unit, Dept Prevent & Predicit Med, Fdn IRCCS, I-20139 Milan, Italy

[16] Univ Naples Federico II, Dept Clin & Expt Med, I-80138 Naples, Italy

[17] Civile MP Arezzo Hosp, Canc Registry, I-97100 Ragusa, Italy

[18] Civile MP Arezzo Hosp, Histopathol Unit, I-97100 Ragusa, Italy

[19] Ctr Canc Prevent CPO Piedmont, I-10123 Turin, Italy

[20] Human Genet Fdn Hugef, I-10126 Turin, Italy

[21] Hlth & Hlth Care Serv Council, Publ Hlth & Participat Directorate, Oviedo 33001, Asturias, Spain

[22] Catalan Inst Oncol ICO, Unit Nutr Environm & Canc, Canc Epidemiol Res Programme, Barcelona 08907, Spain

[23] Andalusian Sch Publ Hlth, Granada 18011, Spain

[24] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona 08003, Spain

[25] Dept Publ Hlth Guipuzkoa, San Sebastian 20013, Spain

[26] Murcia Reg Hlth Author, Dept Epidemiol, Murcia 30008, Spain

[27] Publ Hlth Inst Navarra, Pamplona 31003, Spain

[28] Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands

[29] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands

[30] Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden

[31] Umea Univ, Dept Med Biosci, S-90187 Umea, Sweden

[32] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England

[33] MRC Epidemiol Unit, Cambridge CB2 0QQ, England

[34] Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Clin Med, Oxford OX3 7XP, England

[35] Int Agcy Res Canc, Sect Mech Carcinogenesis, F-69372 Lyon, France

[36] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7, England

来源：

基金：

英国医学研究理事会;

关键词：

C-REACTIVE PROTEIN; INTERLEUKIN-1 RECEPTOR ANTAGONIST; POLYCYSTIC-OVARY-SYNDROME; TYPE-2; DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; ADIPOSE-TISSUE; SERUM-LEVELS; INSULIN-RESISTANCE; GENE-EXPRESSION;

D O I：

10.1677/ERC-10-0053

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P-trend = 0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P-trend = 0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P-trend = 0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (similar to 10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu. Endocrine-Related Cancer (2010) 17 1007-1019

引用

页码：1007 / 1019

页数：13

共 59 条

[1] Inflammation and cancer: How hot is the link? [J].

Aggarwal, Bharat B. ;

Shishodia, Shishir ;

Sandur, Santosh K. ;

Pandey, Manoj K. ;

Sethi, Gautam .

BIOCHEMICAL PHARMACOLOGY, 2006, 72 (11) :1605-1621

[2] Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC) [J].

Allen, Naomi E. ;

Key, Timothy J. ;

Dossus, Laure ;

Rinaldi, Sabina ;

Cust, Anne ;

Lukanova, Annekatrin ;

Peeters, Petra H. ;

Onland-Moret, N. Charlotte ;

Lahmann, Petra H. ;

Berrino, Franco ;

Panico, Salvatore ;

Larranaga, Nerea ;

Pera, Guillem ;

Tormo, Maria-Jose ;

Sanchez, Maria-Jose ;

Quiros, J. Ramon ;

Ardanaz, Eva ;

Tjonneland, Anne ;

Olsen, Anja ;

Chang-Claude, Jenny ;

Linseisen, Jakob ;

Schulz, Mandy ;

Boeing, Heiner ;

Lundin, Eva ;

Palli, Domenico ;

Overvad, Kim ;

Clavel-Chapelon, Francoise ;

Boutron-Ruault, Marie-Christine ;

Bingham, Sheila ;

Khaw, Kay-Tee ;

Bueno-de-Mesquita, H. Bas ;

Trichopoulou, Antonia ;

Trichopoulos, Dimitiros ;

Naska, Androniki ;

Tumino, Rosario ;

Riboli, Elio ;

Kaaks, Rudolf .

[3]

[Anonymous], IARC HDB CANC PREV W

[4]

[Anonymous], 2007, Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective

[5] Interleukin-1 receptor antagonist: Role in biology [J].

Arend, WP ;

Malyak, M ;

Guthridge, CJ ;

Gabay, C .

ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :27-55

[6] Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro [J].

Bastard, JP ;

Maachi, M ;

Van Nhieu, JT ;

Jardel, C ;

Bruckert, E ;

Grimaldi, A ;

Robert, JJ ;

Capeau, J ;

Hainque, B .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (05) :2084-2089

[7] High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer [J].

Bellone, S ;

Watts, K ;

Cane, S ;

Palmieri, M ;

Cannon, MJ ;

Burnett, A ;

Roman, JJ ;

Pecorelli, S ;

Santin, AD .

GYNECOLOGIC ONCOLOGY, 2005, 98 (01) :92-98

[8] Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms [J].

Calle, EE ;

Kaaks, R .

NATURE REVIEWS CANCER, 2004, 4 (08) :579-591

[9] Serum levels of interleukins, growth factors and anglogenin in patients with endometrial cancer [J].

Vimlarani Chopra ;

Tung V. Ding ;

Edward V. Hanningan .

Journal of Cancer Research and Clinical Oncology, 1997, 123 (3) :167-172

[10] Inflammation and cancer [J].

Coussens, LM ;

Werb, Z .

NATURE, 2002, 420 (6917) :860-867

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