Alleles with short CAG and GGN repeats in the androgen receptor gene are associated with benign endometrial cancer

Rodríguez, Germán Vicente; Bilbao, Cristina; Ramírez, Raquel; Falcón, Orlando; León, Laureano; Chirino, Ricardo; Díaz, Blanca P.; Rivero, José Pablo Suárez; Perucho, Manuel; Díaz-Chico, B.N.; Díaz-Chico, J. C.

doi:10.1002/ijc.21516

Cited by 32 publications

(41 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The repeat numbers obtained with fragment analysis have differed when analysing the results on an ABI Prism 3100 Genetic Analyzer using the internal standard supplied by the manufacturer as compared to the results received when using a ladder that has been verified by direct sequencing (Rodriguez et al, 2006). It is therefore important to emphasise that all the genetic analyses in this study were performed with the same method, that is, fragment analysis on an ABI Prism 3100 or a 3130xl Genetic Analyzer, using control samples with lengths verified by direct sequencing.…”

Section: Igf1-19/-mentioning

confidence: 99%

Absence of the common Insulin-like growth factor-1 19-repeat allele is associated with early age at breast cancer diagnosis in multiparous women

et al. 2007

View full text Add to dashboard Cite

Multiparity decreases the risk of breast cancer in white women, whereas it is a risk factor in black women o50 years. Early-onset breast cancer (o50 years) has been associated with high insulin-like growth factor-1 (IGF-1) levels. Absence of the common IGF1 19 cytosine-adenine (CA)-repeat allele (IGF1-19/-19) inverts the effect of several non-genetic factors on breast cancer risk but the interaction between IGF1-19/-19 and multiparity on breast cancer risk is unknown. As IGF1-19/-19, multiparity and early-onset breast cancer are more common in black than in white women, we aimed to study whether multiparity combined with IGF1-19/-19 increases the risk of early-onset breast cancer. Four hundred and three breast cancer patients diagnosed in Lund, Sweden, at age 25 -99 years were genotyped for the IGF1 CA-repeat length using fragment analysis. Overall, 12.9% carried the IGF1-19/-19 genotype. There was a highly significant interaction between multiparity and IGF1-19/-19 on age at breast cancer diagnosis (P ¼ 0.007). Among IGF1-19/-19 patients, multiparity was associated with a 9.2 year earlier age at diagnosis compared with uniparity or nulliparity (P ¼ 0. Breast cancer is the most common malignancy in women worldwide (Parkin et al, 2001(Parkin et al, , 2002. Approximately 10% of women living in Sweden will develop the disease during their lifetime. The median age at breast cancer diagnosis in women in Sweden is 60 years; approximately 4% of women are 40 years or younger at diagnosis (data from the Swedish Cancer Registry). The prognosis is often poorer in younger than in older women (Sidoni et al, 2003) in terms of overall survival and relapse (Han et al, 2004), partly because young women do not benefit from breast cancer screening and early-onset breast cancers are usually detected clinically at a more advanced stage. In Lund, Sweden, mammography screening is initiated at age 45 years and is performed every 18 months until the age of 74 years. As of today, no tests are routinely performed to identify the subgroup of women who do not belong to high-risk breast cancer families (eg BRCA1 families) but who would nevertheless benefit from breast cancer screening at an earlier age owing to an increased risk for early-onset breast cancer.Breast cancer risk is determined by genetic factors and nongenetic factors, for example, reproductive factors (Beral and Reeves, 1993;Kelsey et al, 1993). An increased age at first full-term pregnancy and low parity have been associated with an increased risk of developing breast cancer in the developed world (Kelsey et al, 1993). In the short term, a first full-term pregnancy increases the risk of breast cancer (Beral and Reeves, 1993). Each subsequent live-birth reportedly decreases the risk of breast cancer by 30% and after three full-term pregnancies, the short-term risk of developing breast cancer is similar to the risk of nulliparous women (McCredie et al, 1998). In the long-term, a full-term pregnancy confers a decreased risk of developing breast cancer (McCredie et al, 1998) and ...

show abstract

Section: Igf1-19/-mentioning

confidence: 99%

Absence of the common Insulin-like growth factor-1 19-repeat allele is associated with early age at breast cancer diagnosis in multiparous women

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Clinical and pathological data, and follow-up of patients of this series have been published previously. 45 The mean age of patients was 64 years (range: 29-90 years); there were 182 tumors of endometrioid histological type; 153 tumors were well (n 5 98) or moderately (n 5 55) differentiated; and, 141 patients were diagnosed at stage I.…”

Section: Tumor Samplesmentioning

confidence: 99%

The relationship between microsatellite instability and PTEN gene mutations in endometrial cancer

Bilbao

Rodríguez

Ramírez

et al. 2006

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Microsatellite instability (MSI) and mutations in the PTEN gene are among the molecular alterations involved in endometrial carcinogenesis. There is conflicting information regarding to their role in this type of tumor. For this reason, we have studied both molecular lesions in a large population-based series of 205 patients with sporadic endometrial cancer. MSI was found in 41 (20.0%) of the tumors and PTEN mutations were found in 74 (36.1%). There were differences in genotype between tumors with and without MSI. Tumors with MSI showed both a higher frequency of PTEN mutations (58.5% vs. 30.4%) (p 5 0.002, Fisher's exact test) and a higher number of insertions or deletions (I/D) of one nucleotide within the mononucleotide tracts of the PTEN gene (45.8% vs. 11.4% out of all I/D, p 5 0.005). Conversely, G:C to A:T transitions in CpG dinucleotides were found mostly in microsatellite stable tumors (57.7% vs. 18.2% out of all single-base substitutions, p 5 0.037). Overall, 67.6% of tumors with mutated PTEN exhibited multiple mutations or allelic imbalance (AI). Multiple PTEN mutations in the same tumor were more frequent in tumors with MSI (60% vs. 25.7%); by contrast the presence of AI accompanying PTEN mutation was higher in microsatellite stable tumors (74.3% vs. 40%) (p 5 0.028). In addition, patients with both genetic alterations were diagnosed at more advanced stage of progression (54.2% for MSI vs. 20.0% for MSS, p 5 0.006), and exhibited a worse prognosis (hazard ratio [95% confidence interval]: 3.0 [1.1-13.1], p 5 0.034, log-rank test) than patients with only the PTEN gene mutated. Our data suggest that the DNA mismatch repair system status influences: (i) both the frequency and the mutational spectrum of PTEN; (ii) the nature of one of the hits that inactivate this tumor-suppressor gene; and (iii) the clinical condition and behavior of the patients. ' 2006 Wiley-Liss, Inc.Key words: microsatellite instability; PTEN mutation; endometrial cancer Microsatellite instability (MSI) is caused by defects in the DNA mismatch repair (MMR) system, either by mutations or by epigenetic events leading to gene silencing. 1,2 Tumors with MSI are characterized by a massive instability in simple repeated sequences and mutations in many cancer-related genes, particularly those with simple repeated sequences in their coding regions. [3][4][5][6][7] Tumors with MSI display a strong microsatellite mutator phenotype (MMP), which underlies a mutational pathway for gastrointestinal cancer that differs in genotype and phenotype from cancers with microsatellite stability (MSS).The MMP pathway for colon cancer possesses several peculiar characteristics in genotype. These tumors show a paradoxically low incidence of mutations affecting the prototypical cancer genes for colon cancer, namely the APC and p53 tumor suppressor genes and the K-ras oncogene. 3,[8][9][10][11] This low mutational incidence is also accompanied by a decreased incidence of loss of heterozygosity (LOH), 1,3,12 which is reflected at the cytogenetic level in freque...

show abstract

“…Terry et al (2005) reported that women with two long AR alleles (≥22 CAG repeats) had an increased risk of ovarian cancer compared with those with two short alleles (<22 CAG repeats). However, the results from similar analyses have varied depending on the population and sample size (Sasaki et al, 2003;Rodriguez et al, 2006). In this study, CAG repeat numbers ranged from 14 to 31 in the samples, and the frequency ranged from 0.339 to 24.460%.…”

Section: Discussionmentioning

confidence: 71%

“…The AR gene promoter region contains a polymorphic CAG trinucleotide repeat that encodes an uninterrupted polyglutamine tract in the N-terminal domain, ranging from 6 to 39 repeats in healthy individuals (Buchanan et al, 2004). Shorter CAG repeat length is reported to be associated with increased risk of prostate cancer (Nelson and Witte, 2002), ovarian cancer (Santarosa et al, 2002), BC (Haiman et al, 2002;Suter et al, 2003), and endometrial cancer (Sasaki et al, 2003;Rodriguez et al, 2006). Further studies should be performed to replicate these findings and to evaluate the effects of this AR variation on the risk of BC.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptor (CAG)n polymorphisms and breast cancer risk in a Han Chinese population

et al. 2015

View full text Add to dashboard Cite

ABSTRACT. The androgen receptor (AR) is involved in the differentiation and growth of breast cancer. Genetic markers in the AR gene have a plausible role in modulating the risk of breast cancer. In this study, we studied the association of breast cancer and the trinucleotide repeat polymorphism (CAG)n in exon 1 of the AR gene in 202 patients with breast cancer and 183 healthy controls from our hospital (Yinchuan, China). Repeat lengths were determined by fluorescent DNA fragment analysis using the ABI GeneScan software and DNA sequencing. We detected 17 short tandem repeat alleles in exon 1 in the Han population of Ningxia Province, China. The CAG repeat number ranged from 14 to 31 and the frequency ranged from 0.339 to 24.460%. Generally, (CAG) n repeat lengths <22 were classified as short (S), and those >22 were classified as long (L). No association was found between breast cancer and the S/L (CAG) variants. However, the frequency of the (CAG)25 repeats in the breast cancer group was significantly higher than that 10259 Androgen receptor CAG repeat polymorphisms and breast cancer ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 10258-10266 (2015) in the control group (P = 0.033, odds ratio = 1.790, 95% confidence interval = 1.044-3.069). These findings indicate a role for AR gene (CAG)n variations in breast cancer and might be informative for future genetic or biological studies on breast cancer, although these findings need replication in other populations.

show abstract

Alleles with short CAG and GGN repeats in the androgen receptor gene are associated with benign endometrial cancer

Cited by 32 publications

References 32 publications

Absence of the common Insulin-like growth factor-1 19-repeat allele is associated with early age at breast cancer diagnosis in multiparous women

Absence of the common Insulin-like growth factor-1 19-repeat allele is associated with early age at breast cancer diagnosis in multiparous women

The relationship between microsatellite instability and PTEN gene mutations in endometrial cancer

Androgen receptor (CAG)n polymorphisms and breast cancer risk in a Han Chinese population

Contact Info

Product

Resources

About