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Repeat polymorphisms in ESR2 and AR and colorectal cancer risk and prognosis: results from a German population-based case-control study.

Rudolph A, Shi H, Försti A, Hoffmeister M, Sainz J, Jansen L, Hemminki K, Brenner H, Chang-Claude J - BMC Cancer (2014)

Bottom Line: The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence.Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation.Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test.

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. a.rudolph@dkfz.de.

ABSTRACT

Background: Evidence has accumulated which suggests that sex steroids influence colorectal cancer development and progression. We therefore assessed the association of repeat polymorphisms in the estrogen receptor β gene (ESR2) and the androgen receptor gene (AR) with colorectal cancer risk and prognosis.

Methods: The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence. Colorectal cancer risk associations overall and specific for gender were evaluated using multivariate logistic regression models adjusted for sex, county of residence and age. Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation. Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test.

Results: The average number of ESR2 CA repeats was associated with a small 5% increase in colorectal cancer risk (OR = 1.05, 95% CI 1.01-1.10) without significant heterogeneity according to gender or tumoural ESR2 expression. We found no indication for an association between the AR CAG repeat polymorphisms and risk of colorectal cancer. The ESR2 CA and AR CAG repeat polymorphisms were not associated with overall survival or disease specific survival after colorectal cancer diagnosis.

Conclusions: Higher numbers of ESR2 CA repeats are potentially associated with a small increase in colorectal cancer risk. Our study does not support an association between colorectal cancer prognosis and the investigated repeat polymorphisms.

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Frequencies of the average number of (A) CAG repeats inARand (B) CA repeats inESR2.
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Fig1: Frequencies of the average number of (A) CAG repeats inARand (B) CA repeats inESR2.

Mentions: The distribution of relevant epidemiologic characteristics for women and men are shown in Additional file 1: Table S1. The median follow-up time was 48.4 months in men and 49.9 months in women. For the AR CAG repeat, the genotype was successfully determined in 89.4% of cases and 87.7% of controls. The genotyping error rate calculated from the duplicated samples was 4.1%. Because the AR gene is X-linked, a heterozygous genotype among men indicates a genotyping error. The respective samples (20 cases, 16 controls) were excluded from further analyses. For the ESR2 CA repeat, genotyping was successful in 87.9% of cases and 89.4% of controls. The genotyping error rate was 0.8%. The distribution of genotypes among controls did not significantly deviate from HWE for any of the investigated variants, although this could not be assessed for the AR CAG repeat among male controls (HWE p-value was 0.14 for the AR CAG repeat and 0.98 for the ESR2 CA repeat). The allele frequencies of the AR CAG and the ESR2 CA repeats are shown in Figure 1.Figure 1


Repeat polymorphisms in ESR2 and AR and colorectal cancer risk and prognosis: results from a German population-based case-control study.

Rudolph A, Shi H, Försti A, Hoffmeister M, Sainz J, Jansen L, Hemminki K, Brenner H, Chang-Claude J - BMC Cancer (2014)

Frequencies of the average number of (A) CAG repeats inARand (B) CA repeats inESR2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232639&req=5

Fig1: Frequencies of the average number of (A) CAG repeats inARand (B) CA repeats inESR2.
Mentions: The distribution of relevant epidemiologic characteristics for women and men are shown in Additional file 1: Table S1. The median follow-up time was 48.4 months in men and 49.9 months in women. For the AR CAG repeat, the genotype was successfully determined in 89.4% of cases and 87.7% of controls. The genotyping error rate calculated from the duplicated samples was 4.1%. Because the AR gene is X-linked, a heterozygous genotype among men indicates a genotyping error. The respective samples (20 cases, 16 controls) were excluded from further analyses. For the ESR2 CA repeat, genotyping was successful in 87.9% of cases and 89.4% of controls. The genotyping error rate was 0.8%. The distribution of genotypes among controls did not significantly deviate from HWE for any of the investigated variants, although this could not be assessed for the AR CAG repeat among male controls (HWE p-value was 0.14 for the AR CAG repeat and 0.98 for the ESR2 CA repeat). The allele frequencies of the AR CAG and the ESR2 CA repeats are shown in Figure 1.Figure 1

Bottom Line: The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence.Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation.Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test.

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. a.rudolph@dkfz.de.

ABSTRACT

Background: Evidence has accumulated which suggests that sex steroids influence colorectal cancer development and progression. We therefore assessed the association of repeat polymorphisms in the estrogen receptor β gene (ESR2) and the androgen receptor gene (AR) with colorectal cancer risk and prognosis.

Methods: The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence. Colorectal cancer risk associations overall and specific for gender were evaluated using multivariate logistic regression models adjusted for sex, county of residence and age. Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation. Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test.

Results: The average number of ESR2 CA repeats was associated with a small 5% increase in colorectal cancer risk (OR = 1.05, 95% CI 1.01-1.10) without significant heterogeneity according to gender or tumoural ESR2 expression. We found no indication for an association between the AR CAG repeat polymorphisms and risk of colorectal cancer. The ESR2 CA and AR CAG repeat polymorphisms were not associated with overall survival or disease specific survival after colorectal cancer diagnosis.

Conclusions: Higher numbers of ESR2 CA repeats are potentially associated with a small increase in colorectal cancer risk. Our study does not support an association between colorectal cancer prognosis and the investigated repeat polymorphisms.

Show MeSH
Related in: MedlinePlus