Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer

Stella Koutros, Fredrick R. Schumacher, Richard B. Hayes, Jing Ma, Wen Yi Huang, Demetrius Albanes, Federico Canzian, Stephen J. Chanock, E. David Crawford, W. Ryan Diver, Heather Spencer Feigelson, Edward Giovanucci, Christopher A. Haiman, Brian E. Henderson, David J. Hunter, Rudolf Kaaks, Laurence N. Kolonel, Peter Kraft, Loïc Le Marchand, Elio Riboli & 8 others Afshan Siddiq, Mier J. Stampfer, Daniel O. Stram, Gilles Thomas, Ruth C. Travis, Michael J. Thun, Meredith Yeager, Sonja I. Berndt

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2389-2396
Number of pages8
JournalCancer Research
Volume70
Issue number6
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Prostatic Neoplasms
Confidence Intervals
Alleles
Single Nucleotide Polymorphism
Odds Ratio
Breast Neoplasms
Social Adjustment
National Cancer Institute (U.S.)
Insulin-Like Growth Factor I
Genes
Prostate
Carcinogenesis
Logistic Models
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Koutros, S., Schumacher, F. R., Hayes, R. B., Ma, J., Huang, W. Y., Albanes, D., ... Berndt, S. I. (2010). Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer. Cancer Research, 70(6), 2389-2396. https://doi.org/10.1158/0008-5472.CAN-09-3575

Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer. / Koutros, Stella; Schumacher, Fredrick R.; Hayes, Richard B.; Ma, Jing; Huang, Wen Yi; Albanes, Demetrius; Canzian, Federico; Chanock, Stephen J.; Crawford, E. David; Diver, W. Ryan; Feigelson, Heather Spencer; Giovanucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hunter, David J.; Kaaks, Rudolf; Kolonel, Laurence N.; Kraft, Peter; Le Marchand, Loïc; Riboli, Elio; Siddiq, Afshan; Stampfer, Mier J.; Stram, Daniel O.; Thomas, Gilles; Travis, Ruth C.; Thun, Michael J.; Yeager, Meredith; Berndt, Sonja I.

In: Cancer Research, Vol. 70, No. 6, 15.03.2010, p. 2389-2396.

Research output: Contribution to journalArticle

Koutros, S, Schumacher, FR, Hayes, RB, Ma, J, Huang, WY, Albanes, D, Canzian, F, Chanock, SJ, Crawford, ED, Diver, WR, Feigelson, HS, Giovanucci, E, Haiman, CA, Henderson, BE, Hunter, DJ, Kaaks, R, Kolonel, LN, Kraft, P, Le Marchand, L, Riboli, E, Siddiq, A, Stampfer, MJ, Stram, DO, Thomas, G, Travis, RC, Thun, MJ, Yeager, M & Berndt, SI 2010, 'Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer', Cancer Research, vol. 70, no. 6, pp. 2389-2396. https://doi.org/10.1158/0008-5472.CAN-09-3575
Koutros S, Schumacher FR, Hayes RB, Ma J, Huang WY, Albanes D et al. Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer. Cancer Research. 2010 Mar 15;70(6):2389-2396. https://doi.org/10.1158/0008-5472.CAN-09-3575
Koutros, Stella ; Schumacher, Fredrick R. ; Hayes, Richard B. ; Ma, Jing ; Huang, Wen Yi ; Albanes, Demetrius ; Canzian, Federico ; Chanock, Stephen J. ; Crawford, E. David ; Diver, W. Ryan ; Feigelson, Heather Spencer ; Giovanucci, Edward ; Haiman, Christopher A. ; Henderson, Brian E. ; Hunter, David J. ; Kaaks, Rudolf ; Kolonel, Laurence N. ; Kraft, Peter ; Le Marchand, Loïc ; Riboli, Elio ; Siddiq, Afshan ; Stampfer, Mier J. ; Stram, Daniel O. ; Thomas, Gilles ; Travis, Ruth C. ; Thun, Michael J. ; Yeager, Meredith ; Berndt, Sonja I. / Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer. In: Cancer Research. 2010 ; Vol. 70, No. 6. pp. 2389-2396.
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abstract = "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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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

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AU - Hunter, David J.

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AU - Kolonel, Laurence N.

AU - Kraft, Peter

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AU - Riboli, Elio

AU - Siddiq, Afshan

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AU - Stram, Daniel O.

AU - Thomas, Gilles

AU - Travis, Ruth C.

AU - Thun, Michael J.

AU - Yeager, Meredith

AU - Berndt, Sonja I.

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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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