title: The functional promoter polymorphism (-842G>C) in the PIN1 gene is associated with decreased risk of breast cancer in non-Hispanic white women 55 years and younger.
abstract: 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.
authors.affiliation: Department of Epidemiology, Unit 1365, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Chan H
authors.initials: CH
authors.lastname: Han
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bondy
authors.forename: Abenaa M
authors.initials: AM
authors.lastname: Brewster
authors.forename: Tse-Kuan
authors.initials: TK
authors.lastname: Yu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Banu K
authors.initials: BK
authors.lastname: Arun
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D002277:Carcinoma / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D012907:Smoking / Q000453:epidemiology; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase