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Common single-nucleotide polymorphisms in the estrogen receptor ? promoter are associated with colorectal cancer survival in postmenopausal women.

ABSTRACT: Loss of estrogen receptor ? (ER?) expression in the gut is associated with colorectal cancer (CRC) initiation and progression. Germline single-nucleotide polymorphisms (SNP) in genes for the sex-steroid hormone receptors are not strongly associated with CRC risk; however, these SNPs have not previously been evaluated in relation to survival after diagnosis. We enrolled 729 women, ages 50 to 74, diagnosed with invasive CRC between 1997 and 2002 in 13 counties covered by the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. Participants provided germline DNA. We selected 99 tag-SNPs for the androgen receptor (AR), ER? (ESR1), ER? (ESR2), and progesterone receptor (PGR) genes. Mortality outcomes were ascertained from the National Death Index. During a median of 6.6 years of follow-up, 244 deaths occurred (161 from CRC). We identified 20 SNPs (12 of ESR2 and 8 of PGR) for replication in 1,729 women diagnosed with incident invasive CRC (555 deaths; 405 from CRC) from three prospective cohort studies that participate in the Genetics and Epidemiology of Colorectal Cancer Consortium. Three correlated SNPs in the promoter of ESR2 (rs2987983, rs3020443, and rs2978381) were statistically significant predictors of CRC-specific and overall survival. Minor alleles of each were associated with improved survival [for rs2987983, CRC-specific HR, 0.77; 95% confidence interval (CI), 0.60-0.99 in the initial study, and HR, 0.79; CI, 0.64-0.98 in replication]. No associations were noted for SNPs of AR, ESR1, or PGR. SNPs in the promoter of ESR2 may be important to pathways related to the association between ER? and tumor progression and metastasis.

SUBMITTER: Passarelli MN

PROVIDER: S-EPMC3588850 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Common single-nucleotide polymorphisms in the estrogen receptor β promoter are associated with colorectal cancer survival in postmenopausal women.

Passarelli Michael N MN Phipps Amanda I AI Potter John D JD Makar Karen W KW Coghill Anna E AE Wernli Karen J KJ White Emily E Chan Andrew T AT Hutter Carolyn M CM Peters Ulrike U Newcomb Polly A PA

Cancer research 20121113 2

Loss of estrogen receptor β (ERβ) expression in the gut is associated with colorectal cancer (CRC) initiation and progression. Germline single-nucleotide polymorphisms (SNP) in genes for the sex-steroid hormone receptors are not strongly associated with CRC risk; however, these SNPs have not previously been evaluated in relation to survival after diagnosis. We enrolled 729 women, ages 50 to 74, diagnosed with invasive CRC between 1997 and 2002 in 13 counties covered by the Seattle-Puget Sound Su ...[more]

PMID: 23149914

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Project description:AimTo investigate the relationship between c.343A>G and c.2216A>C polymorphism sites in the CDH17 gene and colorectal carcinoma.MethodsNinety-three non-consanguineous colorectal carcinoma patients admitted to the Department of Oncology at the First Affiliated Hospital of Zhengzhou University were included in this study. Ninety-three peripheral venous blood samples, of approximately one milliliter from each patient, were collected between December 2009 and August 2010. The genomic DNA of these peripheral venous blood samples were extracted and purified using a Fermentas Genomic DNA Purification Kit (Fermentas, CA) according to the manufacturer's protocol. The single nucleotide polymorphisms (SNPs) of the liver-intestine cadherin (CDH17) gene c.343A>G and c.2216A>C were determined by the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP) in 93 peripheral venous blood samples from patients suffering with colorectal carcinoma. Typical samples that showed different migration bands in SSCP were confirmed by sequencing. Directed DNA sequencing was used to check the correctness of the genotype results from the PCR-SSCP method.ResultsThere was a significant association between the c.2216 A>C SNPs of the CDH17 gene and the tumor-node-metastasis (TNM) grade, as well as with lymph node status, in 93 peripheral venous blood samples from colorectal carcinoma patients. The genotype frequencies of A/C, A/A, and C/C were 12.90%, 33.33% and 53.76%, respectively. There was a significant correlation between lymph node metastasis, TNM grade, and the genotype distribution (P < 0.05). The C/C genotype raised the risk of lymph node metastasis and the TNM grade. There was a significant difference in the TNM grade and lymph node metastasis between the A/A and C/C genotypes (P = 0.003 and P = 0.013, respectively). Patients with colorectal carcinoma carrying the C allele tended to have a higher risk of lymph node metastasis and have a higher TNM grade. The difference between the TNM grades, as well as the lymph node metastasis of the two alleles, was statistically significant (P < 0.01).ConclusionThe SNPs of the CDH17 gene c.2216 A>C might be clinically important in the prognosis of colorectal carcinoma.

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Common single-nucleotide polymorphisms in the estrogen receptor ? promoter are associated with colorectal cancer survival in postmenopausal women.

Publications

Common single-nucleotide polymorphisms in the estrogen receptor β promoter are associated with colorectal cancer survival in postmenopausal women.

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