Birth weight, breast cancer susceptibility loci, and breast cancer risk.
BACKGROUND
There is considerable evidence that birth weight is positively associated with breast cancer risk, and seven single-nucleotide polymorphisms (SNPs) have been conclusively associated with this risk. We have hypothesized that breast cancer susceptibility loci may have a greater influence on breast cancer risk among women with higher birth weight, who are expected to have a larger pool of mammary stem cells that are susceptible to malignant transformation.


METHODS
In the context of a nationwide, population-based case-control study in Sweden, we retrieved recorded birth weight for 693 breast cancer cases and 747 control women who were also genotyped for most or all of the seven recently documented breast cancer susceptibility SNPs: rs2981582, rs12443621, rs8051542, rs3803662, rs889312, rs13281615, and rs3817198.


RESULTS
We grouped heterozygotes with homozygotes for the wild-type allele, and we found a marginally significant interaction (p~0.07) between birth weight and rs2981582 (FGFR2), the genotype repeatedly identified as the top hit in genome-wide association studies. There were similar, though not significant, patterns for the other six SNPs.


CONCLUSIONS
Although our findings require confirmation, we found suggestive evidence that genetic susceptibility modifies the positive association of birth weight with breast cancer.
Tamimi
Rulla M
RM
Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
Lagiou
Pagona
P
Czene
Kamila
K
Liu
Jianjun
J
Ekbom
Anders
A
Hsieh
Chung-Cheng
CC
Adami
Hans-Olov
HO
Trichopoulos
Dimitrios
D
Hall
Per
P
D000368:Aged; D001724:Birth Weight; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D013548:Sweden
C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2