STK15 polymorphism and breast cancer risk in a population-based study.
STK15 is considered a potential cancer susceptibility gene owing to its functions in normal cell mitosis. Two common coding region polymorphisms in the gene (F31I and V57I) may affect ubiquitin-dependent degradation and thus the half-life of the encoded protein. There are limited data on the relevance of these polymorphisms to population cancer rates. To examine whether functional variation in STK15 may affect breast cancer risk, we genotyped a large series of incident breast cancer cases (n = 941) and age-matched population controls (n = 830) for the F31I and V57I polymorphisms. Individually, neither the F31I polymorphism [odds ratio (OR) 1.54; 95% confidence interval (CI) 0.96-2.47, comparing 31I with 31F homozygotes] nor the V57I polymorphism (OR 0.92; 95% CI 0.50-1.71, comparing 57I with 57V homozygotes) was significantly associated with breast cancer risk. A relatively common genotype, combining the two polymorphisms (31I-57V/31I-57V, 3% of controls) was related to a significant 2-fold increase in the risk of post-menopausal breast cancer (OR 1.96; 95% CI 1.01-3.79). No interaction was detected between STK15 variants and estrogenic risk factors, although the power of these analyses was limited. These results suggest that STK15 may represent a low penetrance type breast cancer susceptibility gene.
Egan
Kathleen M
KM
Vanderbilt University Medical Center, Suite 6000, MCE, Nashville, TN 37232-8300, USA. kathleen.egan@vanderbilt.edu
Newcomb
Polly A
PA
Ambrosone
Christine B
CB
Trentham-Dietz
Amy
A
Titus-Ernstoff
Linda
L
Hampton
John M
JM
Kimura
Makoto T
MT
Nagase
Hiroki
H
D019943:Amino Acid Substitution; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D015914:Estrogen Replacement Therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006207:Half-Life; D006801:Humans; D015994:Incidence; D008423:Maternal Age; D008938:Mitosis; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D025801:Ubiquitin / Q000378:metabolism; D014481:United States / Q000453:epidemiology
D025801:Ubiquitin; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases