Modifying effects of IL-6 polymorphisms on body size-associated breast cancer risk.
OBJECTIVE
The association between obesity and breast cancer risk is complex. We examined whether the association between body size and breast cancer risk is modified by interleukin-6 (IL6) genotype.


METHODS
Five polymorphisms in the IL-6 gene (rs1800797/-596A>G, rs1800796/-572G>C, rs1800795/-174G>C, rs2069832/IVS2G>A, and rs2069849 exon 5 C>T) were studied. We investigated IL6 genotypes and haplotypes with indicators of body size among non-Hispanic white (NHW) and Hispanic/American Indian (AI) breast cancer cases and controls living in the Southwestern United States.


RESULTS
We observed lower mean levels of BMI among NHW women who carried one or two copies of the GGCAC haplotype (in order: rs1800797, rs1800796, rs1800795, rs2069832, and rs2069849; P trend 0.02). This haplotype, with an estimated frequency of 43% in NHW study controls, was considerably less common in Hispanic/AI controls (19%). We did not detect significant interactions between IL6 genotypes or haplotypes and BMI categorized as low/normal (<25), overweight (25 to <30), or obese (> or =30) and breast cancer risk in either NHW or Hispanic/AI women. However, we detected consistent and significant interactions between waist-to-hip ratio (WHR) and IL6 rs1800795/-174 G>C genotype for breast cancer risk. These associations were restricted to postmenopausal NHW women. Among women without recent hormone exposure, those with a WHR >0.9 and the rs1800795 GG genotype had a greater than threefold increased risk of breast cancer (odds ratios (ORs) 3.22, 95% confidence intervals (CIs) 1.27, 817) when compared with women with a WHR <0.8 and the rs1800795 GG genotype (P interaction 0.01).


CONCLUSIONS
These data suggest that IL-6 genotypes may influence breast cancer risk in conjunction with central adiposity.
Slattery
Martha L
ML
Department of Medicine, University of Utah, Salt Lake City, UT, USA. marty.slattery@hsc.utah.edu
Curtin
Karen
K
Sweeney
Carol
C
Wolff
Roger K
RK
Baumgartner
Richard N
RN
Baumgartner
Kathy B
KB
Giuliano
Anna R
AR
Byers
Tim
T
D050154:Adiposity / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D049628:Body Size / Q000208:ethnology / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006630:Hispanic or Latino / Q000208:ethnology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D015206:Southwestern United States; D049629:Waist-Hip Ratio; D015430:Weight Gain / Q000208:ethnology / Q000235:genetics; D044465:White People / Q000208:ethnology
D015850:Interleukin-6