TY - JOUR
T1 - Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer
AU - Koutros, Stella
AU - Schumacher, Fredrick R.
AU - Hayes, Richard B.
AU - Ma, Jing
AU - Huang, Wen Yi
AU - Albanes, Demetrius
AU - Canzian, Federico
AU - Chanock, Stephen J.
AU - Crawford, E. David
AU - Diver, W. Ryan
AU - Feigelson, Heather Spencer
AU - Giovanucci, Edward
AU - Haiman, Christopher A.
AU - Henderson, Brian E.
AU - Hunter, David J.
AU - Kaaks, Rudolf
AU - Kolonel, Laurence N.
AU - Kraft, Peter
AU - Le Marchand, Loïc
AU - Riboli, Elio
AU - Siddiq, Afshan
AU - Stampfer, Mier J.
AU - Stram, Daniel O.
AU - Thomas, Gilles
AU - Travis, Ruth C.
AU - Thun, Michael J.
AU - Yeager, Meredith
AU - Berndt, Sonja I.
PY - 2010/3/15
Y1 - 2010/3/15
N2 - The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. Thus, we explored the association between single-nucleotide polymorphisms (SNP) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk [ORper allele, 1.08 (95% CI, 1.03-1.14); Ptrend = 0.0017] after adjustment for multiple testing (Padj = 0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association [ORper allele, 1.21 (95% CI, 1.09-1.34); Ptrend = 0.0003]. The adjusted association was stronger for men who were diagnosed before the age of 65 years [OR per allele, 1.47 (95% CI, 1.20-1.79); Ptrend = 0.0001] or had a family history [ORper allele = 1.57 (95% CI, 1.11-2.23); P trend = 0.0114], and was strongest in those with both characteristics [ORper allele = 2.31 (95% CI, 1.07-5.07), P-interaction = 0.005]. Increased risks were observed among men in the top tertile of circulating insulin-like growth factor-I (IGF-I) levels [ORper allele = 1.46 (95% CI, 1.04-2.06); Ptrend = 0.075]. No differences were observed with disease aggressiveness (Gleason grade ≥8 or stage T3/T4 or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early-onset disease, which may be attributable to IGF-dependent PI3K signaling.
AB - The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. Thus, we explored the association between single-nucleotide polymorphisms (SNP) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk [ORper allele, 1.08 (95% CI, 1.03-1.14); Ptrend = 0.0017] after adjustment for multiple testing (Padj = 0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association [ORper allele, 1.21 (95% CI, 1.09-1.34); Ptrend = 0.0003]. The adjusted association was stronger for men who were diagnosed before the age of 65 years [OR per allele, 1.47 (95% CI, 1.20-1.79); Ptrend = 0.0001] or had a family history [ORper allele = 1.57 (95% CI, 1.11-2.23); P trend = 0.0114], and was strongest in those with both characteristics [ORper allele = 2.31 (95% CI, 1.07-5.07), P-interaction = 0.005]. Increased risks were observed among men in the top tertile of circulating insulin-like growth factor-I (IGF-I) levels [ORper allele = 1.46 (95% CI, 1.04-2.06); Ptrend = 0.075]. No differences were observed with disease aggressiveness (Gleason grade ≥8 or stage T3/T4 or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early-onset disease, which may be attributable to IGF-dependent PI3K signaling.
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U2 - 10.1158/0008-5472.CAN-09-3575
DO - 10.1158/0008-5472.CAN-09-3575
M3 - Article
C2 - 20197460
AN - SCOPUS:77950226852
SN - 0008-5472
VL - 70
SP - 2389
EP - 2396
JO - Cancer Research
JF - Cancer Research
IS - 6
ER -