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PIN1, an isomerase that causes conformational changes in proteins, plays an important role in mammary epithelial cell growth both physiologically and pathologically. Thus, genetic variants in the PIN1 gene may alter protein function and cancer risk. We have previously demonstrated an association between a PIN1 promoter variant (-842G>C; rs2233678) and risk of squamous cell carcinoma of the head and neck, a finding supported by additional functional data. In the present study, we genotyped two promoter single nucleotide polymorphisms (SNPs) (-842G>C, rs2233678 and -667T>C, rs2233679) and one synonymous SNP (Gln33Gln; G>A, rs2233682) in exon 2 to evaluate their associations with risk of sporadic breast cancer in non-Hispanic white women 55 years and younger. We found that the carriers of -842C variant alleles had decreased risk of breast cancer with an adjusted odd ratio (OR) of 0.67 and 95% confidence interval (CI) of 0.50-0.90. This reduced risk was more evident in women after reproductive age of 45 (OR = 0.63, 95% CI = 0.42-0.93), ever-smokers (OR = 0.56, 95% CI = 0.36-0.88), and ever-drinkers (OR = 0.67, 95% CI = 0.45-0.99). No such associations were observed for PIN1 -667T>C and PIN1 Gln33Gln. However, the haplotypes of these three SNPs were also associated with reduced risk of breast cancer. In conclusion, the PIN1 polymorphisms may contribute to the etiology of sporadic breast cancer in non-Hispanic white women 55 years and younger. Further validation in large population-based studies is needed.