Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer.
BACKGROUND
The Women's Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects.


METHODS
All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676 women who developed breast cancer during trial follow-up (1993-2005). Case-only analyses were used to estimate odds ratios for the DM intervention in relation to SNP genotype.


RESULTS
Odds ratios for the DM intervention did not vary significantly with the genotype for any of the eight FGFR2 SNPs (P > or = 0.18). However, odds ratios varied (P < 0.05) with the genotype of six of these SNPs, among women having baseline percent of energy from fat in the upper quartile (> or =36.8%). This variation is most evident for SNP rs3750817, with odds ratios for the DM intervention at 0, 1, and 2 minor SNP alleles of 1.06 [95% confidence intervals (95% CI), 0.80-1.41], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33-1.15). The nominal significance level for this interaction is P = 0.005, and P = 0.03 following multiple testing adjustment, with most evidence deriving from hormone receptor-positive tumors.


CONCLUSIONS
Invasive breast cancer odds ratios for a low-fat dietary pattern, among women whose usual diets are high in fat, seem to vary with SNP rs3750817 in the FGFR2 gene.
Prentice
Ross L
RL
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109-1024, USA. rprentic@fhcrc.org
Huang
Ying
Y
Hinds
David A
DA
Peters
Ulrike
U
Cox
David R
DR
Beilharz
Erica
E
Chlebowski
Rowan T
RT
Rossouw
Jacques E
JE
Caan
Bette
B
Ballinger
Dennis G
DG
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000178:diet therapy* / Q000235:genetics*; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects; D005247:Feeding Behavior; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*
D004041:Dietary Fats; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2