PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3).
Genes involved in the inflammation pathway have been associated with cancer risk. Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers. We conducted a study within the Breast and Prostate Cancer Cohort Consortium to examine the association between IL6 and PTGS2 polymorphisms and breast and prostate cancer risk. Twenty-seven polymorphisms, selected by pairwise tagging, were genotyped on 6292 breast cancer cases and 8135 matched controls and 8008 prostate cancer cases and 8604 matched controls. The large sample sizes and comprehensive single nucleotide polymorphism tagging in this study gave us excellent power to detect modest effects for common variants. After adjustment for multiple testing, none of the associations examined remained statistically significant at P = 0.01. In analyses not adjusted for multiple testing, one IL6 polymorphism (rs6949149) was marginally associated with breast cancer risk (TT versus GG, odds ratios (OR): 1.32; 99% confidence intervals (CI): 1.00-1.74, P(trend) = 0.003) and two were marginally associated with prostate cancer risk (rs6969502-AA versus rs6969502-GG, OR: 0.87, 99% CI: 0.75-1.02; P(trend) = 0.002 and rs7805828-AA versus rs7805828-GG, OR: 1.11, 99% CI: 0.99-1.26; P(trend) = 0.007). An increase in breast cancer risk was observed for the PTGS2 polymorphism rs7550380 (TT versus GG, OR: 1.38, 99% CI: 1.04-1.83). No association was observed between PTGS2 polymorphisms and prostate cancer risk. In conclusion, common genetic variation in these two genes might play at best a limited role in breast and prostate cancers.
Dossus
Laure
L
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. l.dossus@dkfz.de
Kaaks
Rudolf
R
Canzian
Federico
F
Albanes
Demetrius
D
Berndt
Sonja I
SI
Boeing
Heiner
H
Buring
Julie
J
Chanock
Stephen J
SJ
Clavel-Chapelon
Francoise
F
Feigelson
Heather Spencer
HS
Gaziano
John M
JM
Giovannucci
Edward
E
Gonzalez
Carlos
C
Haiman
Christopher A
CA
Hallmans
Göran
G
Hankinson
Susan E
SE
Hayes
Richard B
RB
Henderson
Brian E
BE
Hoover
Robert N
RN
Hunter
David J
DJ
Khaw
Kay-Tee
KT
Kolonel
Laurence N
LN
Kraft
Peter
P
Ma
Jing
J
Le Marchand
Loic
L
Lund
Eiliv
E
Peeters
Petra H M
PH
Stampfer
Meir
M
Stram
Dan O
DO
Thomas
Gilles
G
Thun
Michael J
MJ
Tjonneland
Anne
A
Trichopoulos
Dimitrios
D
Tumino
Rosario
R
Riboli
Elio
E
Virtamo
Jarmo
J
Weinstein
Stephanie J
SJ
Yeager
Meredith
M
Ziegler
Regina G
RG
Cox
David G
DG
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics / Q000706:statistics & numerical data; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D014481:United States / Q000453:epidemiology
C508600:IL6 protein, human; D015850:Interleukin-6; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human