Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk: A population-based case-control study

Ann W. Hsing, Anand P. Chokkalingam, Yu Tang Gao, Guan Wu, Xin Wang, Jie Deng, Jiaorong Cheng, Isabell A. Sesterhenn, F. Kash Mostofi, Tzuying Chiang, Yuh Ling Chen, Frank Z. Stanczyk, Chawnshang Chang

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Abstract

In an earlier report, we showed that a shorter CAG repeat length in the androgen receptor (AR) gene is associated with an increased risk of prostate cancer in China, the population with the lowest reported prostate cancer incidence in the world. Because AR coactivators enhance transactivation of AR, in this report we evaluated the relationship of a CAG/CAA repeat length polymorphism in the AIB1/SRC-3 gene (amplified in breast cancer gene 1, a steroid receptor coactivator and an AR coactivator) with prostate cancer risk in a population-based case-control study in China. Genomic DNA from 189 prostate cancer patients and 301 healthy controls was used for the PCR-based assay. The AIB1/SRC-3 CAG/CAA repeat length ranged from 24 to 32, with the most common repeat length being 29. Homozygous 29/29 and heterozygous 28/29 were the most common genotypes, with 44 and 30% of the controls harboring these genotypes, respectively. Relative to subjects homozygous for 29 CAG/CAA repeats (29/29 genotype), individuals with the <29/29 genotype had a nonsignificant 31% increased risk [odds ratio (OR), 1.31; 95% confidence interval (CI), 0.87-1.97], whereas those homozygous for the <29 allele had a significant 81% excess risk (OR, 1.81; 95% CI, 1.00-3.28). The combined effect of CAG repeat lengths in the AR and AIB1/SRC-3 genes was also evaluated. Relative to men with both the 29/29 genotype of the AIB1/SRC-3 gene and a long CAG repeat length (≥23) in the AR gene, those with both the <29/<29 AIB1/SRC-3 genotype and a short CAG repeat length in the AR gene (<23) had a 2.8-fold risk (OR, 2.78; 95% CI, 1.24-6.26). Together, our data indicate that the CAG/CAA repeat length in the AIB1/SRC-3 gene may be associated with prostate cancer risk in Chinese men and that the combination of CAG/CAA repeat lengths in both the AIB1/SRC-3 and AR genes may provide a useful marker for clinically significant prostate cancer. Expanded studies in other populations are needed to confirm this association and the combined effect of AIBI/SRC-3 and other hormone-related genes in prostate cancer etiology.

Original languageEnglish
Pages (from-to)337-341
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume11
Issue number4
Publication statusPublished - 2002 Jan 1

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Androgen Receptors
Case-Control Studies
Prostatic Neoplasms
Odds Ratio
Genotype
Population
Genes
Confidence Intervals
China
Nuclear Receptor Coactivator 1
Neoplasm Genes
Transcriptional Activation
Alleles
Hormones
Breast Neoplasms
Polymerase Chain Reaction
DNA
Incidence

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

Hsing, A. W., Chokkalingam, A. P., Gao, Y. T., Wu, G., Wang, X., Deng, J., ... Chang, C. (2002). Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk: A population-based case-control study. Cancer Epidemiology Biomarkers and Prevention, 11(4), 337-341.
Hsing, Ann W. ; Chokkalingam, Anand P. ; Gao, Yu Tang ; Wu, Guan ; Wang, Xin ; Deng, Jie ; Cheng, Jiaorong ; Sesterhenn, Isabell A. ; Mostofi, F. Kash ; Chiang, Tzuying ; Chen, Yuh Ling ; Stanczyk, Frank Z. ; Chang, Chawnshang. / Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk : A population-based case-control study. In: Cancer Epidemiology Biomarkers and Prevention. 2002 ; Vol. 11, No. 4. pp. 337-341.
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abstract = "In an earlier report, we showed that a shorter CAG repeat length in the androgen receptor (AR) gene is associated with an increased risk of prostate cancer in China, the population with the lowest reported prostate cancer incidence in the world. Because AR coactivators enhance transactivation of AR, in this report we evaluated the relationship of a CAG/CAA repeat length polymorphism in the AIB1/SRC-3 gene (amplified in breast cancer gene 1, a steroid receptor coactivator and an AR coactivator) with prostate cancer risk in a population-based case-control study in China. Genomic DNA from 189 prostate cancer patients and 301 healthy controls was used for the PCR-based assay. The AIB1/SRC-3 CAG/CAA repeat length ranged from 24 to 32, with the most common repeat length being 29. Homozygous 29/29 and heterozygous 28/29 were the most common genotypes, with 44 and 30{\%} of the controls harboring these genotypes, respectively. Relative to subjects homozygous for 29 CAG/CAA repeats (29/29 genotype), individuals with the <29/29 genotype had a nonsignificant 31{\%} increased risk [odds ratio (OR), 1.31; 95{\%} confidence interval (CI), 0.87-1.97], whereas those homozygous for the <29 allele had a significant 81{\%} excess risk (OR, 1.81; 95{\%} CI, 1.00-3.28). The combined effect of CAG repeat lengths in the AR and AIB1/SRC-3 genes was also evaluated. Relative to men with both the 29/29 genotype of the AIB1/SRC-3 gene and a long CAG repeat length (≥23) in the AR gene, those with both the <29/<29 AIB1/SRC-3 genotype and a short CAG repeat length in the AR gene (<23) had a 2.8-fold risk (OR, 2.78; 95{\%} CI, 1.24-6.26). Together, our data indicate that the CAG/CAA repeat length in the AIB1/SRC-3 gene may be associated with prostate cancer risk in Chinese men and that the combination of CAG/CAA repeat lengths in both the AIB1/SRC-3 and AR genes may provide a useful marker for clinically significant prostate cancer. Expanded studies in other populations are needed to confirm this association and the combined effect of AIBI/SRC-3 and other hormone-related genes in prostate cancer etiology.",
author = "Hsing, {Ann W.} and Chokkalingam, {Anand P.} and Gao, {Yu Tang} and Guan Wu and Xin Wang and Jie Deng and Jiaorong Cheng and Sesterhenn, {Isabell A.} and Mostofi, {F. Kash} and Tzuying Chiang and Chen, {Yuh Ling} and Stanczyk, {Frank Z.} and Chawnshang Chang",
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Hsing, AW, Chokkalingam, AP, Gao, YT, Wu, G, Wang, X, Deng, J, Cheng, J, Sesterhenn, IA, Mostofi, FK, Chiang, T, Chen, YL, Stanczyk, FZ & Chang, C 2002, 'Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk: A population-based case-control study', Cancer Epidemiology Biomarkers and Prevention, vol. 11, no. 4, pp. 337-341.

Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk : A population-based case-control study. / Hsing, Ann W.; Chokkalingam, Anand P.; Gao, Yu Tang; Wu, Guan; Wang, Xin; Deng, Jie; Cheng, Jiaorong; Sesterhenn, Isabell A.; Mostofi, F. Kash; Chiang, Tzuying; Chen, Yuh Ling; Stanczyk, Frank Z.; Chang, Chawnshang.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 11, No. 4, 01.01.2002, p. 337-341.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk

T2 - A population-based case-control study

AU - Hsing, Ann W.

AU - Chokkalingam, Anand P.

AU - Gao, Yu Tang

AU - Wu, Guan

AU - Wang, Xin

AU - Deng, Jie

AU - Cheng, Jiaorong

AU - Sesterhenn, Isabell A.

AU - Mostofi, F. Kash

AU - Chiang, Tzuying

AU - Chen, Yuh Ling

AU - Stanczyk, Frank Z.

AU - Chang, Chawnshang

PY - 2002/1/1

Y1 - 2002/1/1

N2 - In an earlier report, we showed that a shorter CAG repeat length in the androgen receptor (AR) gene is associated with an increased risk of prostate cancer in China, the population with the lowest reported prostate cancer incidence in the world. Because AR coactivators enhance transactivation of AR, in this report we evaluated the relationship of a CAG/CAA repeat length polymorphism in the AIB1/SRC-3 gene (amplified in breast cancer gene 1, a steroid receptor coactivator and an AR coactivator) with prostate cancer risk in a population-based case-control study in China. Genomic DNA from 189 prostate cancer patients and 301 healthy controls was used for the PCR-based assay. The AIB1/SRC-3 CAG/CAA repeat length ranged from 24 to 32, with the most common repeat length being 29. Homozygous 29/29 and heterozygous 28/29 were the most common genotypes, with 44 and 30% of the controls harboring these genotypes, respectively. Relative to subjects homozygous for 29 CAG/CAA repeats (29/29 genotype), individuals with the <29/29 genotype had a nonsignificant 31% increased risk [odds ratio (OR), 1.31; 95% confidence interval (CI), 0.87-1.97], whereas those homozygous for the <29 allele had a significant 81% excess risk (OR, 1.81; 95% CI, 1.00-3.28). The combined effect of CAG repeat lengths in the AR and AIB1/SRC-3 genes was also evaluated. Relative to men with both the 29/29 genotype of the AIB1/SRC-3 gene and a long CAG repeat length (≥23) in the AR gene, those with both the <29/<29 AIB1/SRC-3 genotype and a short CAG repeat length in the AR gene (<23) had a 2.8-fold risk (OR, 2.78; 95% CI, 1.24-6.26). Together, our data indicate that the CAG/CAA repeat length in the AIB1/SRC-3 gene may be associated with prostate cancer risk in Chinese men and that the combination of CAG/CAA repeat lengths in both the AIB1/SRC-3 and AR genes may provide a useful marker for clinically significant prostate cancer. Expanded studies in other populations are needed to confirm this association and the combined effect of AIBI/SRC-3 and other hormone-related genes in prostate cancer etiology.

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