Tags

Type your tag names separated by a space and hit enter

Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China.
Cancer Res. 2000 Sep 15; 60(18):5111-6.CR

Abstract

The length of the polymorphic CAG trinucleotide repeat in the polyglutamine region of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Because increased androgenic activity has been linked to prostate cancer and because an ethnic variation exists in the CAG repeat length, this polymorphism has been suggested to explain part of the substantial racial difference in prostate cancer risk. We conducted a population-based case-control study in China to investigate whether CAG and other polymorphisms of the AR gene are associated with clinically significant prostate cancer in this low-risk population. Genomic DNA from 190 prostate cancer patients and 304 healthy controls was used for direct sequencing to evaluate the relationship of CAG and GGN (polyglycine) repeat length in the AR gene. Relative to western men, our study subjects had a longer CAG repeat length, with a median of 23 and only 10% of the subjects having a CAG repeat length shorter than 20. Men with a CAG repeat length shorter than 23 (median length) had a 65% increased risk of prostate cancer (odds ratio, 1.65; 95% confidence interval, 1.14-2.39), compared with men with a CAG repeat length of 23 or longer. For the GGN tract (GGT3GGG1GGT2GGCn), based on the sequencing results from 481 samples, we are the first to show that although GGC regions in the polyglycine tract are highly variable, there are no mutations or polymorphisms in the GGT and GGG regions. More than 72% of the subjects had a GGN repeat length of 23, and those with a GGN repeat length shorter than 23 had a 12% increased risk of prostate cancer (95% confidence interval, 0.71-1.78), compared with those with > or = 23 GGN repeats. Our study not only confirms that Chinese men do have a longer CAG repeat length than western men but also represents the first population-based study to show that even in a very low-risk population, a shorter CAG repeat length confers a higher risk of clinically significant prostate cancer. These results imply that CAG repeat length can potentially serve as a useful marker to identify a subset of individuals at higher risk of developing clinically significant prostate cancer. Larger studies are needed to evaluate the combined effect of CAG and GGN repeats. Because of the significance of AR in prostate cancer, investigation of factors that interact with the polyglutamine region of the AR gene to alter AR function and modulate prostate cancer risk is an important area for future research.

Authors+Show Affiliations

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852-7234, USA. hsinga@exchange.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11016637

Citation

Hsing, A W., et al. "Polymorphic CAG and GGN Repeat Lengths in the Androgen Receptor Gene and Prostate Cancer Risk: a Population-based Case-control Study in China." Cancer Research, vol. 60, no. 18, 2000, pp. 5111-6.
Hsing AW, Gao YT, Wu G, et al. Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Res. 2000;60(18):5111-6.
Hsing, A. W., Gao, Y. T., Wu, G., Wang, X., Deng, J., Chen, Y. L., Sesterhenn, I. A., Mostofi, F. K., Benichou, J., & Chang, C. (2000). Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Research, 60(18), 5111-6.
Hsing AW, et al. Polymorphic CAG and GGN Repeat Lengths in the Androgen Receptor Gene and Prostate Cancer Risk: a Population-based Case-control Study in China. Cancer Res. 2000 Sep 15;60(18):5111-6. PubMed PMID: 11016637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. AU - Hsing,A W, AU - Gao,Y T, AU - Wu,G, AU - Wang,X, AU - Deng,J, AU - Chen,Y L, AU - Sesterhenn,I A, AU - Mostofi,F K, AU - Benichou,J, AU - Chang,C, PY - 2000/10/4/pubmed PY - 2000/10/21/medline PY - 2000/10/4/entrez SP - 5111 EP - 6 JF - Cancer research JO - Cancer Res. VL - 60 IS - 18 N2 - The length of the polymorphic CAG trinucleotide repeat in the polyglutamine region of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Because increased androgenic activity has been linked to prostate cancer and because an ethnic variation exists in the CAG repeat length, this polymorphism has been suggested to explain part of the substantial racial difference in prostate cancer risk. We conducted a population-based case-control study in China to investigate whether CAG and other polymorphisms of the AR gene are associated with clinically significant prostate cancer in this low-risk population. Genomic DNA from 190 prostate cancer patients and 304 healthy controls was used for direct sequencing to evaluate the relationship of CAG and GGN (polyglycine) repeat length in the AR gene. Relative to western men, our study subjects had a longer CAG repeat length, with a median of 23 and only 10% of the subjects having a CAG repeat length shorter than 20. Men with a CAG repeat length shorter than 23 (median length) had a 65% increased risk of prostate cancer (odds ratio, 1.65; 95% confidence interval, 1.14-2.39), compared with men with a CAG repeat length of 23 or longer. For the GGN tract (GGT3GGG1GGT2GGCn), based on the sequencing results from 481 samples, we are the first to show that although GGC regions in the polyglycine tract are highly variable, there are no mutations or polymorphisms in the GGT and GGG regions. More than 72% of the subjects had a GGN repeat length of 23, and those with a GGN repeat length shorter than 23 had a 12% increased risk of prostate cancer (95% confidence interval, 0.71-1.78), compared with those with > or = 23 GGN repeats. Our study not only confirms that Chinese men do have a longer CAG repeat length than western men but also represents the first population-based study to show that even in a very low-risk population, a shorter CAG repeat length confers a higher risk of clinically significant prostate cancer. These results imply that CAG repeat length can potentially serve as a useful marker to identify a subset of individuals at higher risk of developing clinically significant prostate cancer. Larger studies are needed to evaluate the combined effect of CAG and GGN repeats. Because of the significance of AR in prostate cancer, investigation of factors that interact with the polyglutamine region of the AR gene to alter AR function and modulate prostate cancer risk is an important area for future research. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11016637/Polymorphic_CAG_and_GGN_repeat_lengths_in_the_androgen_receptor_gene_and_prostate_cancer_risk:_a_population_based_case_control_study_in_China_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11016637 DB - PRIME DP - Unbound Medicine ER -