The progesterone receptor Val660-->Leu polymorphism and breast cancer risk.
BACKGROUND
Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine-->leucine, at codon 660), is associated with a decreased risk for breast cancer.


METHODS
Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay.


RESULTS
We did not observe any association of breast cancer risk with carrying the G/T (Val660-->Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93-1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously.


CONCLUSIONS
Overall, our study does not support an association between the Val660-->Leu PROGINS polymorphism and breast cancer risk.
De Vivo
Immaculata
I
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. nhidv@channing.harvard.edu
Hankinson
Susan E
SE
Colditz
Graham A
GA
Hunter
David J
DJ
D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007930:Leucine / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D011980:Receptors, Progesterone / Q000235:genetics*; D014633:Valine / Q000235:genetics
D011980:Receptors, Progesterone; D007930:Leucine; D014633:Valine