bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1326: Oral enclomiphene citrate lowers IGF-1 in men with secondary hypogonadism while raising testosterone: Implications for cancer prevention.
Authors: Wiehle Ronald D. , Fontenot Gregory K. 
Published: August 2014

Abstract
Introduction: Lowered hGH and IGF-1 have been linked with protection from various cancers.
Methods and Subjects: We determined levels of IGF-1 and pituitary hormones in men with secondary hypogonadism under treatment with enclomiphene (a.k.a. Androxal) in comparison to topical testosterone (T) or placebo. Three, randomized, blinded, phase II studies evaluating daily oral Androxal were performed: ZA-201 investigated 12 men taking 25mg of Androxal in comparison to a gel for 6 months, ZA-202 enrolled 119 diabetic men taking 12.5 or 25 mg Androxal versus placebo for 3 months, and ZA-204 investigated 47 men taking 6.25mg, 12.5mg and 25mg Androxal versus another gel for 6 weeks. All subjects had initial total T &lt;350 ng/dL and low-to-normal LH (&lt;12 IU/L). Serum samples were taken for T, LH and FSH before and after dosing. We could not measure hGH directly but measured its marker, liver-produced IGF-1.
Results: All treatments raised T into the normal range (300-1000 ng/dL), but placebo did not in ZA-202. Androxal elevated LH and FSH. Gels decreased LH and FSH strongly. Unexpected was the strong action of Androxal to lower serum IGF-1 in all three trials. Both Androxal and topicals lowered serum IGF-1 but Androxal was more effective. An example is given from ZA-204 below. Dose groups showed no differences in IGF-1 before (p = 0.94) but significance after treatment (p = 0.03),
Conclusions: Endocrine profile indicate that enclomiphene citrate stimulates the pituitary, resulting in increased LH and FSH and eventually T. The results on IGF-1 cannot be attributed to T since topicals, when used, raised T but not IGF-1 whereas only enclomiphene citrate raised T but lowered IGF-1. Enclomiphene citrate is different from topicals and may be a new way to relieve low T in men with an intact hypothalamus-pituitary-testicular axis. If Androxal can lower hGH or IGF-1 in aging men at risk for prostate cancer, its use in men with secondary hypogonadism is an important new treatment.
Effect of Treatment on IGF-1 dose subjects IGF-1 (SD)before IGF-1 (SD) after Versus Gel MMW 6.25mg 12 101 (43) 54 (30) p&lt;0.01 12.5mg 10 94 (47) 50 (24) p&lt;0.005 25mg 12 96 (45) 62 (42) p&lt;0.01 Gel 13 103 (46) 90 (34)
Citation Format: Ronald D. Wiehle, Gregory K. Fontenot. Oral enclomiphene citrate lowers IGF-1 in men with secondary hypogonadism while raising testosterone: Implications for cancer prevention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1326. doi:10.1158/1538-7445.AM2013-1326
Abstract 1328: Evaluation of common genetic variants in 15 colorectal cancer susceptibility loci among African Americans .
Authors: Zhang Ben , Cai Qiuyin , Long Jirong , Li Guoliang , Signorello Lisa B. , Shrubsole Martha J. , Blot William J. , Zheng Wei 
Published: August 2014

Abstract
Background: Genome-wide association studies (GWAS) conducted primarily in populations of European ancestry, have identified multiple single-nucleotide polymorphisms (SNPs) at 15 loci associated with colorectal cancer (CRC) risk. Limited studies have been conducted to evaluate the association of these SNPs with colorectal neoplasia risk in African Americans.
Methods: We analyzed 19 SNPs within 15 CRC loci in African Americans recruited from two studies, including 206 CRC cases and 1,000 controls from the Southern Community Cohort Study (SCCS), and 203 colorectal adenoma cases and 461 controls from the Tennessee Colorectal Polyp Study (TCPS). Logistic regressions were used to derive adjusted odds ratios and their 95% confidence intervals for the associations between SNPs and disease risk. We also performed a meta-analysis including 1,586 cases and 2,956 controls regarding the association of 11 SNPs with colorectal neoplasia risk in African Americans.
Results: In the combined analysis of data from the SCCS and TCPS, we found two SNPs (rs10505477 and rs6983267) at 8q24 to be significantly associated with colorectal neoplasia risk (P &lt; 0.05). Two additional SNPs, rs7758229 (SLC22A3) and rs4444235 (14q22), showed marginally significant associations with colorectal neoplasia (P &lt; 0.10). In the meta-analysis including data from this study and two other studies, rs16892766 (8q23), rs6983267 (8q24), and rs7014346 (8q24) were significantly associated with colorectal neoplasia with no evidence of heterogeneity across studies.
Conclusions: Genetic variants at 8q23 and 8q24 identified in GWAS conducted in European descendants may also be associated with colorectal neoplasia risk in African Americans.
Impact: Findings from this study may be helpful for future studies to fine-map GWAS-identified loci to identify causal variants for CRC.
Citation Format: Ben Zhang, Qiuyin Cai, Jirong Long, Guoliang Li, Lisa B. Signorello, Martha J. Shrubsole, William J. Blot, Wei Zheng. Evaluation of common genetic variants in 15 colorectal cancer susceptibility loci among African Americans . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1328. doi:10.1158/1538-7445.AM2013-1328
Abstract 1329: PSPHL and breast cancer in African American women: Causativegene or population stratification.
Authors: Rummel Seth , Penatzer Cayla , Shriver Craig D. , Ellsworth Rachel E. 
Published: August 2014

Abstract
Background: The phophoserine phosphatase-like (PSPHL) gene, first identified as overexpressed in fibroblasts from patients with
Fanconi anemia, is expressed at significantly higher levels in breast tumors as well as stromal tissues from African American women (AAW) compared to Caucasian women (CW). The function of PSPHL has not been determined, thus how overexpression of PSPHL impacts tumor etiology or contributes to outcome disparities in African American women is unclear. Here, we evaluated the molecular mechanisms driving expression differences between populations to determine whether expression differences are causative or represent population stratification.
Methods: A PCR-based approach was used to detect the retention or deletion of a 30-kb segment of 7p11 that includes the first three exons of PSPHL. Genotypes were determined using genomic DNA from AAW with invasive breast cancer (n=220), AAW without breast cancer (n = 352) and CW with invasive breast cancer (n=508). Gene expression levels were evaluated by
qRT-PCR using RNA isolated from breast tumors from 52 CW and 43 AAW. Genotype frequencies were analyzed using chi-square analysis and gene expression levels by a Mann-Whitney U-test;
P&lt;0.05 was used to define significance.
Results: Gene expression levels were correlated with the presence or absence of the 30-kb deletion of 7p11: patients homozygous for the deletion had no detectable expression of PSPHL, while patients heterozygous for the deletion had expression levels 2.5-fold lower than those homozygous for retention of PSPHL. When the frequency of the deletion was evaluated by ethnicity, 62% of CW were homozygous for the deletion of PSPHL compared to 5% of AAW with invasive breast cancer (P&lt;0.00005). In contrast, genotype frequencies did not differ significantly between AAW with invasive breast cancer compared to AAW controls (P=0.116).
Conclusions: The deletion of 30-kb of chromosome 7p11 prevents expression of PSPHL. The prevalence of the deletion allele is 77% in CW compared to 23% in AAW, suggesting that this 30-kb deletion and subsequent disruption of PSPHL may be a derived trait in Caucasians. Although the deletion frequency and associated expression differ significantly between
AAW and CW with invasive breast cancer, the similar frequency of the deletion allele in AAW with and without invasive breast cancer suggests that these genetic differences represent population stratification, and do not contribute to outcome differences between AAW and CW with breast cancer.
Citation Format: Seth Rummel, Cayla Penatzer, Craig D. Shriver, Rachel E. Ellsworth. PSPHL and breast cancer in African American women: Causativegene or population stratification. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1329. doi:10.1158/1538-7445.AM2013-1329
Abstract 1336: A population-based study of Transforming Growth Factor-Beta1 (TGFB1) polymorphisms and risk of breast cancer.
Authors: Bewick Mary A. , Conlon Michael SC 
Published: August 2014

Abstract
Transforming growth factor-beta1 (TGFB1) is a multifunctional cytokine that may play an important role in the development and progression of cancer. The results of a number of association studies of TGFB1 polymorphisms and breast cancer risk are inconclusive. This study examined 4 single nucleotide polymorphisms (SNPs) in TGFB1 and risk of breast cancer using data previously collected from a population based case-control study (n=307 cases and 664 controls) of Caucasian women conducted in Northeastern Ontario, Canada. The SNPs (rs8179181, rs8110090, rs1800470 (L10P), rs1800469 (-509C/T)) were selected as either tag SNPs or had been identified as potentially functional in other studies, and were analysed using Taqman genotyping assays. Two of the SNPs were at the 5’ end (rs1800469 (-509C/T), rs1800470) and were in high LD (D’ 0.98); the remaining SNPs (rs8179181, rs8110090) were at the 3’ end and were also in high LD (D’ 0.99). In single-SNP analyses, the variant homozygous genotypes in rs1800470 (CC) and rs8179181 (AA) were significantly protective in the codominant model with Odds Ratios (OR) and 95% Confidence Intervals (95% CIs) of 0.63 (0.40-0.99) and 0.45 (0.21-0.96), while the AG genotype of rs8110090 was significantly associated with increased breast cancer risk with an OR of 1.78 (95% CI 1.14-2.77). Of the seven estimated haplotypes, 3 were significantly protective for breast cancer; when compared to the referent haplotype (see Table). In conclusion, our results suggest that SNPs at both the 3’ and 5’ end of TGFB1 may be associated with risk of breast cancer, and future studies examining additional polymorphisms in these regions would be valuable.
Haplotype association with breast cancer risk (n = 969; Global Haplotype Association p-value 0.0021)rs8179181rs8110090rs1800470rs1800469FrequencyOR (95% CI)P-value1GATC0.40281.002GACT0.23870.73 (0.55–0.97)0.033AATC0.17280.67 (0.48–0.93)0.0174GACC0.06710.49 (0.30–0.81)0.00545AACT0.0560.55 (0.30–1.00)0.0526GGTC0.02981.00 (0.48–2.09)0.997GGCT0.02271.82 (0.82–4.06)0.14
Citation Format: Mary A. Bewick, Michael SC Conlon. A population-based study of Transforming Growth Factor-Beta1 (TGFB1) polymorphisms and risk of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1336. doi:10.1158/1538-7445.AM2013-1336
Abstract 1342: Genetic variations in the MUC16 gene encoding tumor marker CA125 and their association with the risk of epithelial ovarian cancer.
Authors: Williams Kristina , Terry Kathryn , Vitonis Allison , Cramer Daniel 
Published: August 2014

Abstract
Purpose: MUC16 is a cell surface mucin that is expressed at high levels by epithelial ovarian tumors, and is detected in serum as the CA125 antigen. MUC16 is clinically used as a tumor marker in the management of ovarian cancer and has been associated with prognosis. MUC16 is also thought to play an important role in ovarian tumor cell survival and metastasis. We studied the association of four tagging SNPs of the MUC16 gene (rs2547065 (C/G), rs1559168 (A/T), rs2121133 (A/G), rs2121133 (A/G)) and risk of ovarian cancer as well as the correlation of these SNPs with CA125 levels.
Methods: MUC16 polymorphisms were genotyped using blood samples collected from 760 women diagnosed with ovarian cancer and 788 healthy controls enrolled in the New England Case-Control Study between 2003 and 2008. 388 cases had preoperative CA125 levels abstracted from medical records. Odds ratios and 95%CIs were calculated using logistic regression; polytomous (multinomial) logistic regression was used to estimate multivariate odds ratios by ovarian cancer histological subtype. The association between log normalized pre-operative CA125 levels and MUC 16 SNPs was evaluated using generalized linear models.
Results: A significant association was observed between the rs2547065 polymorphism and ovarian cancer risk (per allele: OR=1.30, 95% CI: 1.11-1.52). The risk was greatest for women carrying two copies of the variant allele (OR=1.78, 95% CI: 1.29-2.45). When stratified by histological subtype, these associations were most apparent in the recessive model for women with serous invasive (OR = 1.69; 95%CI: 1.15-2.48) and clear cell (2.49 95% CI: 1.13-5.52) tumors. There were no significant associations between the other three MUC16 SNPs (rs1559168, rs2121133, rs12984471) and ovarian cancer risk. The rs2547065 polymorphism was not found to be associated with pre-operative CA125 levels in cases overall or in the subset of women with serous and clear cell cancers.
Conclusions: These results suggest that women who carry one or more variant alleles of MUC16 SNP rs2547065 have an increased risk of ovarian cancer of the serous invasive and clear cell histological subtype. Further study of MUC 16 SNPs in relation to risk of ovarian cancer and their effect on CA125 levels is warranted.
Citation Format: Kristina Williams, Kathryn Terry, Allison Vitonis, Daniel Cramer. Genetic variations in the MUC16 gene encoding tumor marker CA125 and their association with the risk of epithelial ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1342. doi:10.1158/1538-7445.AM2013-1342
Abstract 1353: KIR copy-number variation and cutaneous melanoma risk.
Authors: Nelson Heather H. , Vineretsky Karin , Lazovich DeAnn 
Published: August 2014

Abstract
Prevention of cutaneous malignant melanoma requires the identification and clearance of abnormal, pre-cancerous cells by the immune system. Central to this immune surveillance is the interplay between KIR receptors present on natural killer cells and their HLA ligands expressed on target cells. Like HLA, the KIR genes are highly polymorphic. They encode both activating receptors (that trigger NK-cell mediated killing), and inhibitory receptors (important in NK cell education and self-tolerance). Many of the KIR genes occur as copy number variants, and we hypothesize that inter- individual variability in KIR copy number is associated with melanoma risk. A random sample of cases and controls within the large, population-based Minnesota Skin Health Study were selected for examination (84 cases and 87 controls). Using Luminex technology and genomic DNA isolated from subject buccal cells we tested for the presence or absence of specific KIR genes (KIR3DL1, KIR2DS1, KIR2DL2, KIR2DL3, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4 {truncating allele}, KIR2DS5, KIR2DS1). In addition to investigating each gene as a melanoma risk factor, we created an integrated locus score for 2DL2/DL3 and 3DL1/DS1, reflecting the typical mutual exclusivity of these genes at their respective loci. Results: Homozygous deletion of the activating KIR gene 2DS1 was associated with both an increasing number of nevi (p&lt;0.04), and increased melanoma risk (OR 2.2, 95% CI 1.2 - 4.3). Similarly, at the shared 3DL1/3DS1 locus, absence of the activating KIR3DS1 gene was significantly associated with increased melanoma risk (OR 2.0, 95% CI 1.0 - 3.3), and a borderline significant increase in the number of nevi (p&lt;0.07). In contrast, at the KIR2DL2/2DL3 locus, which encodes two inhibitory KIR alleles, our data suggest that a lack of diversity at this locus may be more important than the presence or absence of either gene; individuals homozygous for either 2DL2 or 2DL3 were at increased risk for both nevi (p&lt;0.03), and melanoma (OR 1.8, 95% CI 1.0 - 3.4) relative to those who had both 2DL2 and 2DL3. These novel analyses at the complex KIR locus indicate that absence of certain activating KIR receptors, and balance in diversity of KIR inhibitory receptors are important determinants of cutaneous melanoma risk.
Citation Format: Heather H. Nelson, Karin Vineretsky, DeAnn Lazovich. KIR copy-number variation and cutaneous melanoma risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1353. doi:10.1158/1538-7445.AM2013-1353
Abstract 1355: Biospecimen preferences of African-American cancer survivors for cancer genetic research.
Authors: Ewing Altovise T. , Erby Lori AH , Ricks-Santi Luisel J. , Kalu Nnenna , Scott Denise M. 
Published: August 2014

Abstract
Background: Research based on large population-based biobanks has potential to ameliorate health disparities attributed to biological and genetic differences. Study goals were to identify associations of cancer survivors’ sample preferences with sociodemographic characteristics and familiarity with genetic research and testing.
Methods: Information was analyzed on a convenience sample of 158 adult African-American breast, colon or prostate cancer survivors who expressed a willingness to provide a biospecimen for cancer genetic research. Information was collected from a self-directed instrument that measured: 1) demographics, 2)familiarity with genetic research and testing, and 3)willingness to provide a variety of sample types. Descriptive statistics and bivariate chi-square analyses were utilized.
Results: Sample preference variation (N=158) consisted of: 65%, 62% and 18% willing to donate blood, saliva and tissue, respectively. One third (n= 53) endorsed willingness to provide only one form of biological sample (blood, saliva, or tissue). Significant associations were detected between willingness to provide tissue and individuals &lt; 50 years of age (p=0.04). Sample preferences were not otherwise related to age at cancer diagnosis, gender, income, educational status, or familiarity with genetic testing or genetic research.
Conclusions/Impact: Providing options of acceptable biological sample types may yield increased donation from minorities. Inadvertently, this may introduce quality control challenges in obtaining sufficient or multiple forms of biological samples. Identifying additional predictive factors for samples preferences may lead to improvements in methods used to obtain biospecimens from minority populations.
Citation Format: Altovise T. Ewing, Lori AH Erby, Luisel J. Ricks-Santi, Nnenna Kalu, Denise M. Scott. Biospecimen preferences of African-American cancer survivors for cancer genetic research. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1355. doi:10.1158/1538-7445.AM2013-1355
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1358: Are physician recommendations for BRCA 1/2 testing among breast cancer patients appropriate? A population based study.
Authors: McCarthy Anne Marie , Demeter Mirar Bristol , Fredricks Tracey , Liao Kaijun , Shea Judy A. , Groeneveld Peter , Domchek Susan M. , Armstrong Katrina 
Published: August 2014

Abstract
Purpose: To evaluate the rates and predictors of physician recommendation for BRCA 1/2 testing in breast cancer patients.
Patients and Methods: Women aged 18-64 diagnosed with invasive breast cancer in 2007 in Pennsylvania completed a survey on family history of cancer, physician treatment recommendations, and BRCA 1/2 testing (N=2258). Based on age at diagnosis and family history, women were categorized as high, moderate, or low risk for BRCA 1/2 mutations. Multivariate logistic regression was used to assess the odds of physician recommendation for BRCA 1/2 testing by risk group, age at diagnosis, demographics, and tumor characteristics.
Results: Nearly 25% of participants were at high risk for carrying a BRCA 1/2 mutation based on age at breast cancer diagnosis and family history of breast and/or ovarian cancer. Physician recommendations for BRCA 1/2 testing were strongly associated with risk of carrying a BRCA 1/2 mutation, with 53% of women at high risk reporting a testing recommendation compared to 9% of women at low risk. In addition, physician recommendations were strongly correlated with use of testing in all risk groups. Among women at high risk of mutation, lack of a recommendation for BRCA 1/2 testing was more common among women who were older, had lower income, and were employed.
Conclusion: Although BRCA 1/2 testing recommendations appear to be appropriately correlated with mutation risk among women with breast cancer, a significant proportion of breast cancer patients who meet criteria for BRCA 1/2 testing may not be receiving recommendations for such testing from their providers.
Citation Format: Anne Marie McCarthy, Mirar Bristol Demeter, Tracey Fredricks, Kaijun Liao, Judy A. Shea, Peter Groeneveld, Susan M. Domchek, Katrina Armstrong. Are physician recommendations for BRCA 1/2 testing among breast cancer patients appropriate? A population based study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1358. doi:10.1158/1538-7445.AM2013-1358