bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 872: Skin cancers in African albinos: A cause for public concern
Authors: Ademola Samuel A. , Olawoye Olayinka A. , Oluwatosin Odunayo M. , Iyun Ayodele O.
Published: February 2011

Purpose: Skin cancers are uncommon in the black Africans and as such there is little or no formal preventive program against skin cancer in most parts of Africa. In Albinos who live in tropical Africa however, skin cancers are not uncommon and their effects could be devastating. The aim of this report therefore is to evaluate the occurrence of skin cancers in albinos and to highlight the factors that make skin cancers in them a public health issue.

Methods: All patients with clinical suspicion of skin cancers presenting to a major tertiary center in Nigeria were referred to the plastic surgery division of the hospital for evaluation. The chart of all albinos referred to this division between 1989 and 2009 were reviewed. Analysis was done with the aid of Statistical Package for the Social Sciences (SPSS) computer software.

Results: There were 32 patients comprising 20 males and 12 females. Most of the patients were either unemployed or engaged in a low income earning occupation. The mean duration of symptoms at the time of presentation was 21.3 months. Many had multiple lesions at presentation with an average of 3 lesions per patient. The average diameter of the lesions was 8.8cm. Over 80% of the lesions were ulcerated and were located in the head and neck region. Majority of the patients had associated lymph node and surrounding contiguous tissues involvement and therefore requires major reconstructive surgery following tumor excision.

Conclusion: Skin cancers constitute a major health concern in albinos who live in tropical Africa. Majority of the patients present with advanced disease that require major reconstructive surgery for disease control. There is need for institution of educational programs on preventive measures and early medical consultation in order to reduce the tumor burden in this region.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 872.
Abstract 874: Low plasma coenzyme Q10 levels and breast cancer risk in Chinese women: Influence of menopausal status
Authors: Cooney Robert V. , Dai Qi , Gao Yu-Tang , Chow Wong-Ho , Shu Xiao-Ou , Li Honglan , Ji Butian , Cai Qiuyin , Franke Adrian A. , Zheng Wei
Published: February 2011

Coenzyme Q10 (CoQ10) is an essential component of mitochondrial ATP synthesis and an important cellular antioxidant. Decreased circulating levels of CoQ10 have been associated with increased cancer incidence and poor prognosis for a number of cancer types. Limited clinical data suggest that supplemental CoQ10 may benefit breast cancer patients, as evidenced by regression of cancer and increased survival. We prospectively examined the association of plasma CoQ10 with breast cancer risk in a nested case-control study within the Shanghai Women's Health Study. Pre-diagnostic plasma samples were obtained from 373 cases and 740 age-matched controls and analyzed for total CoQ10 by HPLC with UV detection after precolumn coulometric oxidation. A risk reduction of borderline significance was associated with increasing plasma CoQ10 level using a conditional logistic regression model adjusted for age. Analysis by menopausal status revealed approximately a 50% reduction in odds ratio for pre-menopausal women in the highest quartiles of plasma CoQ10 compared to those with the lowest (p for trend = 0.01). In contrast, no significant reduction in risk was observed for post-menopausal women with increasing plasma CoQ10. Adjustment of the model for age, education, age at menarche, age at 1st live birth, months of breast feeding, history of fibroadenoma, first degree family cancer history, smoking history, and use of hormone replacement therapy yielded similar results: a significant inverse trend for breast cancer risk with increasing plasma CoQ10 in pre-menopausal women (p = 0.03) and no association for post-menopausal women. The data suggest that future epidemiologic studies of CoQ10 and breast cancer for pre-menopausal women are warranted and highlight the need for greater understanding of the origins and physiologic meaning of circulating CoQ10 in humans. This work was supported by NIH Grants CA 132149 (RVC), CA106591 (QD), and CA70867 (WZ).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 874.
Abstract 881: Clinical usefulness of soluble fibrin monomer-fibrinogen complex (SFMC) for the metastasis of malignant neoplasm
Authors: Yoshihiro Komatsu , Koga Shin , Orita Hajime , Sakurada Mutsumi , Maekawa Hiroshi , Moriwaki Minoru , Sato Kouichi
Published: February 2011

Objective: SF is a complex coupling fibrin monomer and fibrinogen molecules to be formed in the early-activated state of blood coagulation. The level of SF reflects the thrombin generation activity in plasma. There is increasing evidence that SFMC is expected to serve as a parameter for thrombus formation and DIC, in particular its early stage.

Thrombin generation is activated in the metastasis of malignant neoplasm,

The aim of this study is to determine whether the SF could be a new marker for the metastasis of malignant neoplasm.

Material and Methods: From 2007 to 2008, a total of 86 patients who underwent radical surgery for treatment to the cancer of digestive organs (including cancer of esophagus, stomach, colon, rectum, liver, biliary tract, and pancreas) were enrolled in this study.

We measured SF together with established tumor markers before the surgery and every three months after the surgery. Each of them was compared with imaging tests such as CT scan, ultrasounds, MRI, PET-CT, GIF, and CF.

Results: There were not admitted the rise of SF neither before nor after surgery in the case of stage1 and 2. No metastasis was admitted with the imaging tests in the cases of stage1 and 2, either. In the cases of stage3 and 4, there were some cases with the rise of SF before the surgery. The decrease of SF and tumor markers were admitted in the cases of excising the radical cure. SF was not high in the some cases with relapse or metastasis which condition was considered to be suppressed by chemotherapy and radiotherapy. Moreover, the rise of SF was admitted in all samples in the case of multiple liver metastasis and multiple peritoneal dissemination.

Conclusions: Though this study suggests that SF could be a parameter for the condition of metastatic malignant neoplasm, it has not been systematically studied whether SF is useful for early detection of metastasis and relapse or not.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 881.
Abstract 882: Serum Hsp27 levels may serve as a prognostic biomarker in patients with localized breast cancer: A preliminary report
Authors: De Asit K. , Banerjee Sanjib , Lin Chuen-Fu , Skinner Kristin , Schiffhauer Linda , Peacock James , Huston Alissa , Shayne Michelle , Strickland Jennifer , O'Donoghue Lauren
Published: February 2011

Although there exist some prognostic biomarkers (eg, CA 15-3) for evaluation of responses to therapy in metastatic breast cancer patients, there is no reliable biomarker for early stage breast cancer patients. Heat shock protein 27 (Hsp27) has been reported as elevated in many human cancers of carcinoma origin. We have simultaneously tested serum levels of Hsp27 and CA 15-3 by specific ELISA in 49 untreated breast cancer patients (age→52.77±1.28) with early to locally advanced disease [Stage I (n=21), IIA and B (n=21), IIIA, B and C (n=7)] and 37 female controls (age→50.86±1.60). Hsp27 levels were significantly (p<0.0001) increased in these patients (894.76±116.45 pg/ml) as compared to controls (301.34±44.73 pg/ml). In contrast, CA 15-3 levels, the most characterized and frequently used prognostic biomarker for evaluation of metastatic breast cancer patients’ clinical responses to therapy, showed no increase in these patients (16.36±1.07 U/ml) as compared to controls (16.67±1.27 U/ml). Serum Hsp27 levels were modestly but not significantly elevated in stage III patients (1091.1±486.6 pg/ml) as compared to stage I (887.7±125.6 pg/ml) or II (836.3±188.8 pg/ml) patients. Similarly, serum Hsp27 levels were modestly (not significant) elevated in high grade patients (973.2±180.9 pg/ml; n=22) as compared to low (836.1±212.9 pg/ml; n= 15) or intermediate (824.1±230.1 pg/ml; n=12) grade patients. Although the serum Hsp27 levels were not significantly higher in Stage III or high grade patients as compared to early stage or lower grade patients respectively, post - surgery follow-up serum Hsp27 data are highly encouraging. We have followed 22 patients upto 12 months post - surgery (sample collection at pre-surgery, 6 and 12 months post-surgery). These patients’ pre-surgery Hsp27 levels (995.50±189.74 pg/ml) were significantly (p<0.0002) elevated as compared to healthy controls, but were reduced to almost control levels as tested at 6 (484.32±73.85 pg/ml) and 12 (490.49±119.70 pg/ml) months post-surgery. Thus, our data strongly suggest the possibility of using serum Hsp27 levels as a prognostic biomarker to evaluate clinical responses to therapy in early stage to locally advanced breast cancer patients.

Work supported by ACS RSG-06-266-01-LIB awarded to A. De

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 882.
Abstract 886: Genetic polymorphisms in telomere pathway genes may potentially impact breast cancer survival
Authors: Shen Jing , Gammon Marilie D. , Terry Mary Beth , Wang Qiao , Bradshaw Patrick T. , Teitelbaum Susan L. , Neugut Alfred I. , Santella Regina M.
Published: February 2011

Genetic polymorphisms are not only responsible for disease susceptibility, but may also play a role in determining cancer survival. We examined the associations between genetic variants of 9 genes involved in the telomere pathway in peripheral blood leucocytes (PBLs) and survival among breast cancer cases obtained from a population-based study – the Long Island Breast Cancer Study Project (LIBCSP). Fifty-two genetic variants were analyzed in the current study. Univariate and multivariate Cox regression analysis were used to test telomere length, genotyping and survival relationships. Telomere length had no significant relationship with overall and breast cancer specific mortality. Carrying genetic variants of the POT1 (rs7784168) A-allele and the TERT (rs2853677) TT genotype were significantly associated with increased all-cause mortality. The HRs were, respectively, 2.17 (95%CI: 1.01-4.66) and 1.73 (95%CI: 1.21-2.45) after adjusting for age at diagnosis (continuous), BMI (<25 vs. ≥25) and ER/PR status (both positive vs. either negative). The TERT (rs2853677) TT genotype alone was also significantly related with increased breast cancer specific mortality (HR=1.95, 95%CI: 1.24-3.06) after adjusting for age at diagnosis (continuous), BMI and ER/PR status. For ER/PR negative breast cancer cases, carrying the TERT (rs2735940) TT genotype was significantly associated with decreased breast cancer survival after adjusting for age at diagnosis (continuous), ethnicity (black vs. non-black) and BMI. The HR was 2.43 (95%CI: 1.30-4.55). Among ER and PR positive patients, carrying PINX1-33 (rs2277130) G-allele and the TERT-14 (rs2853677) TT genotype were also significantly associated with decreased breast cancer survival after adjusting for age at diagnosis (continuous). The HRs were 3.30 (95%CI: 1.35-8.06) and 2.56 (95%CI: 1.26-5.19), respectively. These data strongly suggest that genetic variants in telomere pathway genes (PINX1, POT1 and TERT) are potential valuable markers in predicting breast cancer survival.

Acknowledgments

Grant support: National Cancer Institute and National Institute of Environmental Health Sciences grants R03CA125768, U01CA/ES66572, P30ES009089 and P30ES10126; and awards from the Breast Cancer Research Foundation, and Women At Risk (WAR).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 886.
Abstract 888: Reduced folate carrier gene polymorphism (RFC 80G>A): Associations with clinical outcome in NMYC amplified neuroblastoma patients
Authors: Lau Diana T. , Murray Jayne , Norris Murray , Marshall Glenn M. , Haber Michelle , Ashton Lesley J.
Published: February 2011

Background

Folate plays an important role in cell function, division and differentiation. Gene polymorphisms in the folate pathway have been shown to influence folate uptake and metabolism. The aims of our study were to examine how specific gene variants in the folate pathway influence the clinical outcome of childhood neuroblastoma and to measure the correlation between specific genotypes and levels of gene expression.

Methods

Common single nucleotide polymorphisms (SNPs) in the folate pathway were examined in DNA from 174 children diagnosed with neuroblastoma between 1985 and 2000. Cox proportion hazard analysis was used to investigate the association between the presence or absence of specific gene polymorphisms and the risk of relapse or death in the 5 year follow up period, while adjusting for known prognostic cofactors. Relative quantification of reduced folate carrier (RFC) mRNA expression was performed in a subset of 43 neuroblastoma tissues by real-time quantitative PCR.

Results

No significant difference in EFS was observed between individuals with different folate genotypes (P>0.05). However, in multivariate analysis children homozygous for the RFC 80A gene variant were significantly less likely to relapse or die compared to those with RFC 80G allele after adjusting for prognostic factors such as NMYC status, stage and age at diagnosis (HR=0.46; 95% CI=0.24-0.90, P=0.024). Moreover, in those patients with NMYC amplification, the cumulative 5 year EFS was 0% in those homozygous for RFC 80GG; 9% in those heterozygous for RFC 80GA; and 50% in those homozygous for RFC 80AA (Log-rank test, P=0.005). However, no apparent association was observed for any of the additional gene polymorphisms examined (P>0.05) even after adjusting for NMYC status, age, or tumour stage at diagnosis. Quantitative mRNA analysis in a subset of 43 patients showed that expression of RFC was three times higher in those with RFC 80GG genotype compared to those with other genotypes, although this was not statistically significant (P=0.587).

Conclusions

Our results show that the RFC 80A variant allele confers superior survival in patients with NMYC amplification. These findings suggest that the RFC G80A polymorphism may play an important role in modifying folate transport in rapidly dividing neuroblastoma cells regulated by NMYC proto-oncogene.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 888.
Abstract 89: BamBam: Simultaneous processing of tumor and germline sequencing data
Authors: Sanborn John Z. , Haussler David
Published: February 2011

With the release of multiple fully-sequenced tumor and matched normal genomes from The Cancer Genome Atlas (TCGA), there is great need for tools that can efficiently analyze these enormous datasets. To this end, we developed BamBam, a method that interfaces with the SAMtools library to simultaneously analyze a patient's tumor and germline genomes using short-read alignments stored in SAM/BAM-formatted files. BamBam enables an efficient calculation of regional copy number, loss of heterozygosity (LOH), and the discovery of both somatic and germline sequence variants and structural rearrangements. Chromosomal regions that experience single copy loss or copy neutral LOH are used to phase heterozygous sites and construct germline haplotypes.

We used BamBam to analyze the short-read sequencing data of several glioblastoma multiforme and ovarian serous carcinoma tumors produced by the TCGA genome sequencing centers at the Broad Institute and Washington University in St. Louis. In each tumor, BamBam identified somatic homozygous and heterozygous small indels and single nucleotide variants, inferred regions exhibiting large-scale loss of heterozygosity, estimated relative copy number, and identified sites of structural variation. The intra- and inter-chromosomal rearrangements we infer are often found at the boundary of copy number alterations, implicating homology-driven mechanisms. We identified variants shared by more than one tumor as well as events restricted to individual tumors. Strikingly, in each tumor processed thus far, distinct regions of localized chromosomal instability were observed. The inferred haplotypes share substantial regions of identity with the germline haplotypes of the other TCGA samples and phased SNPs from samples of 11 HapMap populations, indicating they have high accuracy.

BamBam is a computationally efficient method for surveying large sequencing datasets to produce a set of high-quality genomic events that occur within each tumor relative to its germline. These results provide a glimpse into the chromosomal dynamics of tumors, improving our understanding of these tumors’ final states and the events that led to them.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 89.
Abstract 894: Genetic variations in the angiogenesis pathway modulate clinical outcomes of bladder cancer
Authors: Chen Meng , Lerner Seth , McConkey David , Gu Jian , Kamat Ashish , Grossman H. Barton , Dinney Colin P. , Wu Xifeng
Published: February 2011

Bladder cancer is the fourth most common cancer in men in the United States. There is compelling evidence suggesting that a patient's genetic background contributes to bladder cancer clinical outcome. Angiogenesis is an essential process required for tumor development, growth, and metastasis. We hypothesized that genetic variations in the angiogenesis pathway may affect the overall survival of bladder cancer patients. We conducted a follow-up study of 397 non-muscle invasive and 320 muscle-invasive bladder cancer patients to systematically evaluate 458 single nucleotide polymorphisms (SNPs) in 24 angiogenesis pathway genes as predicators of prognosis and BCG response. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by multivariate Cox proportional hazard regression adjusting for age, gender, stage, grade, and treatment regimen. In non-muscle invasive bladder cancer patients, no significant SNPs were identified after correction for multiple comparisons. When stratified by BCG treatment, variant KIT rs11735550 was significantly associated with recurrence in patients who did not receive BCG treatment (HR=2.84, 95%CI: 1.67-4.83). In muscle-invasive bladder cancer patients, variant FLT4 rs11750142, rs2447737, rs13168072, and rs11739750 genotypes, and wild-type rs11957360 were significantly associated with increased risk of dying. These SNPs are not in linkage disequilibrium suggesting that each one independently modulates survival. In addition, a significant gene dosage effect was observed for increased risk with increasing number of unfavorable genotypes (P for trend<0.001). Compared to the low-risk group (0-1 unfavorable genotypes), median-risk group (2-3 unfavorable genotypes) and high-risk group (4-5 unfavorable genotypes) showed 1.34- (95%CI: 0.86-2.11) and 2.60-fold (95%CI: 1.66-4.09) increased risk of dying, respectively. In Kaplan-Meier estimates, the low-, median-, and high-risk groups had significantly different median survival time (MST) of 81.9, 67.9, and 31.3 months, respectively (logrank P <0.01). These results support the hypothesis that genetic variations in the angiogenesis pathway modulate clinical outcomes for bladder cancer patients. These findings warrant further replication in independent populations, and could be useful in disease management and the development of targeted therapies for bladder cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 894.
Abstract 895: NFκB and IκBKB polymorphisms and colorectal cancer survival in the Seattle Colon Cancer Family Registry
Authors: Coghill Anna E. , Newcomb Polly A. , Poole Elizabeth M. , Duggan Dave , Makar Karen W. , Ulrich Cornelia M.
Published: February 2011

Introduction: IκBKB and NFκB are regulatory enzymes that interact with the prostaglandin synthesis pathway, which plays a key role in inflammation and colorectal carcinogenesis. Transcriptional targets of the nuclear factor NFκB have been linked to cellular proliferation, angiogenesis, and metastasis. IκBKB binds NFκB within the cytoplasm and can prevent its nuclear localization. The role of variability in these genes in relation to colorectal cancer (CRC) survival has not been investigated; we therefore examined polymorphisms in both IκBKB and NFκB in relation to CRC survival.

Methods: CRC cases were ascertained from 1997-2002 from the Seattle Colon Cancer Family Registry and were matched through linkages to the National Death Index records to obtain date and cause of death. A subgroup of CRC cases was genotyped for selected tagSNPs (9 in IκBKB; 44 in NFκB), including non-synonymous candidate polymorphisms (IκBKB: rs17875749, rs2272736; NFκB: rs4648072, rs4648099). Cox proportional hazards regression models were used to estimate hazard ratios investigating the relationship between polymorphisms in IκBKB and NFκB and CRC-specific mortality.

Results: We observed statistically significant inverse associations between four SNPs in IκBKB (rs11986055, rs2272733, rs6474387, and rs9694958) and the risk of CRC mortality after diagnosis. The observed survival benefit ranged from 86% reduced CRC mortality risk for rs11986055 (HR AA vs. AC or CC: 0.14, 95% CI 0.02-1.03) to 59% reduced CRC mortality risk for rs2272733 (HR GG vs. GA or AA: 0.41, 95% CI 0.20-0.82). The functional significance of these SNPs is unknown; none of these SNPs were in high linkage disequilibrium, with all r2 values < 0.7. No SNPs investigated in NFκB were significantly associated with colorectal cancer survival.

Conclusion: These data suggest that certain polymorphisms in IκBKB may be associated with mortality from colorectal cancer after diagnosis.Associations between IκBKB polymorphisms and CRC survival Hazard Ratio95% CIp-valueAliveDeaadrs11986055 A>C     AA1.00Ref. 20279AC or CC0.140.02-1.030.05241rs2272733 G>A     GG1.00Ref. 17571GA or AA0.410.20-0.820.01519rs6474387 C>T     CC1.00Ref. 18875CT or TT0.400.16-1.000.05365rs9694958 A>G     AA1.00Ref. 18874AG or GG0.370.16-0.860.02386All models reported above adjusted for age, sex, and stage of disease at diagnosis     

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 895.
Abstract 896: Pre-diagnostic blood fatty acid levels and prostate cancer mortality
Authors: Chavarro Jorge E. , Stampfer Meir J. , Campos Hannia , Sesso Howard D. , Ma Jing
Published: February 2011

Purpose: Fatty acid metabolism, particularly de novo lipogenesis, may be an important determinant of prostate cancer progression and mortality. However, epidemiologic data regarding the role of circulating fatty acids, as biomarkers of fatty acid intake and metabolism, on prostate cancer progression and mortality is scarce.

Methods: We conducted a prospective cohort study among 582 Physicans’ Health Study participants who provided a blood sample in 1982 and who were later diagnosed with prostate cancer, between 1982 and 2006. Blood samples were kept frozen until they were assayed. Men were followed from the date of prostate cancer diagnosis until death or the end of follow-up (March 31, 2009). Blood levels of major types of fatty acids were measured using gas chromatography and expressed as percentage of total fatty acids. Men were categorized according to quintiles of blood fatty acid levels. Proportional hazards regression was used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of prostate cancer specific mortality in a given quintile of fatty acid level in relation to the lowest quintile.

Results: During 7,414 person-years of follow-up, 94 men died of prostate cancer. The median time between diagnosis and prostate cancer death was 14 years. The median time between blood draw and prostate cancer diagnosis was 9.5 years. Blood levels of all the mono-unsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids examined were unrelated to prostate cancer mortality. However, compared to men in the lowest quintile, the RRs (95% CIs) of prostate cancer mortality for men in increasing quintiles of blood stearic acid (18:0) levels were 1.90 (0.81-4.50), 3.61 (1.55-8.42), 2.29 (0.96-5.43) and 4.96 (2.10-11.7) (P, trend <0.001) after adjusting for age at diagnosis, race, body mass index, smoking status, clinical stage and tumor grade at diagnosis, and time between blood draw and prostate cancer diagnosis. Blood levels of the remaining saturated fatty acids examined were unrelated to prostate cancer mortality.

Conclusions: Pre-diagnostic blood levels of stearic acid, a saturated fatty acid, are positively related to prostate cancer mortality. Since blood stearic acid levels are usually unrelated to diet, these data suggest that differences in fatty acid metabolism might be responsible for this association. It remains to be determined whether this finding is due to between-person differences in the activity of de novo lipogenesis enzymes or other metabolic factors that result in higher blood levels of stearic acid.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 896.
Abstract 902: Associations between methylenetetrahydrofolate reductase polymorphisms and survival in patients with colorectal cancer treated with 5-FU-based adjuvant chemotherapy: A thirteen years follow-up study
Authors: Yeh Chih-Ching , Chang Shih-Ni , Sung Fung-Chang , Hsieh Ling-Ling , Tang Reiping
Published: February 2011

PURPOSE

The study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and overall survival (OS) of patients with colorectal cancer (CRC) treated with 5-Fluorouracil (5-FU)-based chemotherapy.

PATIENTS AND METHODS

We genotyped MTHFR polymorphisms (C677T and A1298C) for 530 CRC patients treated with 5-FU-based chemotherapy after receiving surgery between 1995 and 1999. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan-Meier curve. The association between MTHFR genotypes and survival was analyzed using Cox proportional hazard models and haplotype analysis.

RESULTS

After 13 years follow-up, the median survival year was 4.77 (95% CI, 4.0 to 6.1). The OS was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR = 0.77; 95% CI, 0.61 to 0.98). Although no association was found between the MTHFR A1298C polymorphism and OS in CRC, this polymorphism showed significant differences in OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with the AC+CC genotypes than those with the AA genotype (HR = 1.94; 95% CI, 1.34 to 2.80). In haplotype analysis, better survival was related to colon patients carrying the MTHFR 677T-1298A haplotype, but worse survival was linked to rectal cancer carrying the MTHFR 677C-1298C haplotype.

CONCLUSION

To our knowledge, our study is the largest to investigate the relationship between MTHFR polymorphisms and OR in CRC patients in a Chinese population. Our findings suggest that MTHFR genotypes provide prognostic information in CRC patients treated with 5-FU-based chemotherapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 902.
Abstract 903: Long-term survivors in advanced non-small cell lung cancer
Authors: Fujiuchi Satoru , Fujita Yuka , Nishigaki Yutaka , Nakanishi Kyoko , Yamamoto Yasushi , Takeda Akinori , Yamazaki Yasuhiro , Fujikane Toshiaki
Published: February 2011

Background:

It is known that chemotherapy for advanced non small-cell lung cancer (NSCLC) improves the prognosis, however, with regard to 2-year survival rate of inoperable stage III/IV patients is up to 20%. The contribution of chemotherapies for survival is not fully satisfied yet.

Purpose:

The aim of this study is to evaluate the rate of long-term survival of more than 2 years in patients with advanced NSCLC and elucidate clinical factors that affect long-term survival in those patients.

Methods:

We retrospectively reviewed 103 patients with inoperable, stage III/IV NSCLC treated with chemotherapy from January 2005 to December 2006 at Dohoku National Hospital. These included 69 adenocarcinomas, 22 squamous cell carcinomas, 9 large cell carcinomas and 3 others. These patients were divided into two groups: those who survived more than 2 years (long-term survivors; LTS) and the others (non long-term survivors; non LTS). We analyzed the prognostic factors that affect the survival in this setting. The difference of characteristics between two groups was tested with the Mann-Whitney U test, the chi-square test or Fisher's exact test. Survival curves were calculated according to Kaplan-Meier method. The correlations of variables with survival were analyzed by multivariate analysis using a Cox proportional hazards model.

Results:

There were 27 (26.2%) patients who survived more than 2 years (LTS). All of them had performance status (PS) 0 or 1. These LTS included 13 females, 11 non-smoker, 21 adenocarcinomas and 17 stage IV disease. LTS showed significant correlation with gender, smoking status, intrapulmonary metastases, response of 1st-line chemotherapy (SD or better), and response of gefitinib (SD or better) (p=0.0008, p=0.0457, p=0.0317, p=0.0004 and p=0.0026, respectively). Patients who respond to initial chemotherapy (SD or better) as well as gefitinib showed favorable course. Univariate analyses showed that PS 0-1, intrapulmonary metastases, response of 1st-line chemotherapy (SD or better), response of gefitinib (SD or better) were significantly associated with better prognosis (p=0.0036, p=0.0203, p<0.0001 and p=0.0090, respectively). Multivariate analyses showed absence of bone metastases, response of 1st-line chemotherapy (SD or better), response of gefitinib (SD or better) were significantly associated with good prognosis (p=0.0031, p<0.0001 and p=0.0028, respectively). Conclusions: Absence of bone metastases, response of 1st-line chemotherapy and response of gefitinib are the significant factors to predict better prognosis in patients with advanced non-small cell lung cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 903.
Abstract 905: Associations with breast cancer survival replicated for three SNPs: A report from the Shanghai Breast Cancer Survival Study and Shanghai Breast Cancer Study
Authors: Beeghly-Fadiel Alicia C. , Long Jirong , Gao Yutang , Zheng Ying , Cai Qiuyin , Gu Kai , Chen Zhi , Lu Wei , Zheng Wei , Shu Xiao Ou
Published: February 2011

We have previously reported associations between nine single nucleotide polymorphisms (SNPs) and breast cancer outcomes from the Shanghai Breast Cancer Study (SBCS, Stage I). We evaluated these SNPs in association with overall survival (OS) and disease free-survival (DFS) among participants of the Shanghai Breast Cancer Survival Study (SBCSS) and participants of the second phase of SBCS (Stage 2). The mean follow-up time of the 1,115 Stage 1 participants was 6.5 years; the mean follow-up time of the 5,381 Stage 2 participants was 4.2 years. Models of effect and subgroup analyses were conducted based on published results from Stage 1. A missense SNP in exon 1 of TGFβ1 (rs1800470) was associated with improved overall survival in a recessive fashion (p-value = 0.028). Minor allele homozygotes (TT) fared slightly better than major allele carriers (CT and CC) (OS hazard ratio (HR): 0.8, 95% confidence interval (CI): 0.6-1.0); this effect was slightly attenuated after adjustment for known prognostic factors including age, disease stage, tumor estrogen and progesterone receptor status, and disease treatment (p-value = 0.052). A SNP downstream of the MMP7 gene (rs11225297), in high linkage disequilibrium with a nearby functional SNP, was associated with improved overall survival in an additive manner (p-value = 0.013). Compared to major allele homozygotes (AA), heterozygotes (AT) fared moderately better (OS HR: 0.8, 95% CI: 0.7-1.0), while homozygotes (TT) fared much better (OS HR: 0.5, 95% CI: 0.3-1.0); this affect was strengthened by adjusting for known covariates (p-value = 0.002). Finally, a functional promoter SNP in MMP8 (rs11225395) was found to be associated with better prognosis among early stage patients (TNM less than 3) in a dominant manner (p-value = 0.007). Early stage minor allele carriers (CT and TT) had better survival (DFS and OS HRs: 0.7, 95% CI: 0.5-0.9); these effects were unaltered by adjusting for covariates (p-values = 0.012). In summary, we were able to replicate associations with breast cancer survival for three of nine previously reported SNPs. These findings suggest that genetic polymorphism in genes governing the tumor microenvironment may play an important role in breast cancer prognosis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 905.
Abstract 908: Genetic variants in one-carbon metabolism related genes contribute to NSCLC prognosis in a Chinese population
Authors: Guangfu Jin , Hu Zhibin , Shen Hongbing
Published: February 2011

One-carbon metabolism plays a critical role in both DNA methylation and DNA synthesis. Genetic variants of genes coding enzymes involved in one-carbon metabolism may result in aberrant methylation and/or DNA synthesis inhibition, and ultimately modulate the initiation and progression of tumors. In the present study, we hypothesized that polymorphisms in one-carbon metabolism related genes may contribute to the prognosis of non-small cell lung cancer (NSCLC). To test this hypothesis, we screened 57 potentially functional single nucleotide polymorphisms (SNPs) from 11 candidate genes involved in one-carbon metabolism and genotyped them in a cohort of 568 NSCLC patients by using Illumina Golden Gate platform. Kaplan-Meier method with log-rank test and Cox proportional hazard models were used for the survival analyses. We found that variant alleles were significantly associated with favorable survivals of NSCLC for MTR rs3768160 A>G (allelic hazards ratio (HR) = 0.78, 95% confidence interval (CI): 0.62-0.98), MTRR rs2966952 G>A (allelic HR = 0.84, 95%CI: 0.71-0.99) and DHFR rs1650697 G>A (allelic HR = 0.83, 95%CI: 0.70-0.99), and with unfavorable prognosis for MTHFD1 rs1950902 G>A with borderline significance (allelic HR = 1.18, 95%CI: 0.99-1.40). In addition, the combined genotypes of above four SNPs showed a locus-dosage effect on NSCLC survival (P for trend = 6.9 × 10−5). In the final multivariate Cox regression model, combined genotypes were identified as an independent prognostic factor for NSCLC with adjusted HR of 0.78 (95% CI: 0.66-0.92; P = 3.7 × 10−3). These findings indicate that genetic variants in one-carbon metabolism pathway may be candidate biomarkers for NSCLC prognosis.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 908.
Abstract 911: Genetic variations in the one-carbon transfer pathway and aberrant DNA methylation in prostate cancer
Authors: Watanabe Masatoshi , Hirokawa Yoshifumi , Suzuki Hiroyoshi , Ichikawa Tomohiko , Katoh Takahiko , Sugimura Yoshiki , Shiraishi Taizo
Published: February 2011

Many molecular studies have indicated that genetic and epigenetic alterations are important for carcinogenesis in the prostate. Alterations in the one-carbon metabolism pathway can influence DNA synthesis and DNA methylation. Polymorphisms in the genes for the methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), serine hydroxymethyltransferase (SHMT) have been reported to be associated with some forms of malignancies. In a case-control study of 300 cases and 240 controls, we investigated whether four common polymorphisms in the MTHFR (C677T and A1298T), MTR (A2756G), SHMT1 (C1420T), MTRR (A66G), reduced folate carrier (RFC-1, A80G), and methylenetetrahydrofolate-dehydrogenase (MTHFD, G1958A) may have a role in altering prostate cancer susceptibility. The genotype was mainly determined by the PCR-RFLP method. The MTHFR 677TT genotype was associated with a significant decrease in the risk with an adjusted odds ratio of 0.57 (95% confidence interval: 0.34-0.94). The RFC-1 80GG genotype was associated with a significant increase in the risk with an adjusted odds ratio of 1.75 (95% confidence interval: 1.07-2.87). However, the MTHFR A1298C, MTR A2756G and SHMT1 C1420T, MTRR A66G and MTHFD G1958A were not associated with prostate cancer risk. We also analyzed CpG island hypermethylation in five genes (GSTP1, RARβ2, AR, DAPK, TIMP-3 and hMLH1) and its association with these polymorphisms in 100 prostate cancers. However no significant association was detected. These findings suggest that polymorphism of the MTHFR may be involved in carcinogenesis of the prostate.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 911.
Abstract 912: Soy isoflavone intake, MDM2 gene polymorphism and breast cancer risk among Chinese women in Singapore
Authors: Koh Woon-Puay , Wang Renwei , Van Den Berg David , Yuan Jian-Min , Yu Mimi C.
Published: February 2011

Epidemiologic studies among populations that consume moderate to high amount of soy have shown that soy isoflavones may reduce breast cancer risk, and the chemopreventive effects are postulated to be related to the anti-estrogenic properties of soy isoflavones. Recently, experimental studies have revealed that dietary isoflavones may also down-regulate the expression of the MDM2 oncogene, and the inhibition of the expression of the MDM2 oncoprotein has in turn been associated with antitumor activities in breast cancer models. Furthermore, a polymorphism in the promoter region of MDM2 SNP309 (T>G change at nucleotide 309 in the first intron; rs2279744) leads to increased expression of the oncogene and has been associated with earlier onset of breast cancer. We have previously shown that postmenopausal women with a higher than median intake of soy have a reduced risk of breast cancer compared with those with a lower intake. If down-regulation of the MDM2 oncogene is one of the mechanistic pathways for the chemopreventive effects of soy isoflavones in breast cancer, we postulate that the protective effect of soy isoflavones on breast cancer will be stronger in those possessing the high-activity MDM2 genotype. To confirm this hypothesis, we conducted a nested case-control study among 281 incident, postmenopausal breast cancer cases and 462 postmenopausal control subjects within the Singapore Chinese Health Study Cohort. Overall, there was no significant association between MDM2 gene polymorphism and breast cancer risk. Postmenopausal women who had a higher than median intake of soy had a reduced risk of breast cancer [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.56-1.03]. This inverse association was principally noted among women homozygous for the high activity MDM2 allele (GG genotype). There was a statistically significant, roughly 50% reduction in breast cancer risk between above versus below median level of soy consumption in this subgroup of women (OR, 0.52; 95% confidence interval, 0.28-0.98). On the other hand, a much weaker, and statistically nonsignificant association was noted among women possessing the lower-activity MDM2 genotypes (OR, 0.86, 95% CI, 0.59-1.24). Our findings suggest that the ability of soy isoflavones to down-regulate the MDM2 oncoprotein may be one etiologic mechanism through which the intake of soy is associated with breast cancer protection.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 912.
Abstract 915: Xenobiotic metabolizing gene variants, occupational chemical exposures, and renal cell cancer
Authors: Heck Julia E. , Lee Yuan-Chin A. , McKay James D. , Hung Rayjean J. , Karami Sara , Gaborieau Valerie , Szeszenia-Dabrowska Neonila , Zaridze David G. , Lissowska Jolanta , Rudnai Peter , Mates Dana , Foretova Lenka , Janout Vladimir , Bencko Vladimir , Chow Wong-Ho , Rothman Nathaniel , Moore Lee E. , Brennan Paul , Boffetta Paolo
Published: February 2011

The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer. Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer.

The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case-control study conducted between 1998 and 2003 across seven centers in central and eastern Europe. The study centers were in the Czech Republic (Ceske, Prague, Olomouc, Brno), Poland (Lodz), Romania (Bucharest), and Russia (Moscow). Incident cases of primary kidney cancer were recruited and underwent an in-person interview in which detailed data were collected on demographics as well as work history and occupational exposure to chemical agents. Genes (cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT)) were selected for the present analysis based on their putative role in xenobiotic metabolism. Genotyping (874 cases and 2396 controls) was conducted with a GoldenGate® Oligo Pool All (OPA) assay by Illumina® and the 5’ nuclease assay (Taqman, Applied Biosystems). Haplotypes were calculated using fastPhase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusted for country of residence, age, and sex.

We observed an increased risk of renal cell cancer (RCC) with two NAT1 SNPs (NAT1A40T, OR=1.36, CI 1.00, 1.86; NAT1R187Q, OR=1.65, CI 1.01, 2.71) and with CYP1B1V432L (OR=1.14, CI 1.01, 1.28). The slow (NAT1*14) phenotype was associated with increased risk of RCC (OR=1.69, CI 1.00-2.86) in comparison to normal phenotype (NAT1*4, *3, *11). Among persons with NAT1*14 phenotype, occupational exposure to trichloroethylene (OR=9.94, CI 1.15, 86.1) and chlorinated solvents (OR=9.79, CI 1.13, 84.8) conferred an increased risk of RCC. Among those with the CYP1B1V432L variant, occupational exposure to trichloroethylene (OR=1.68, CI 1.21, 2.34) and chlorinated solvents (OR=1.58, CI 1.14, 2.19) also had increased risk of RCC.

These results require replication, but provide evidence that the relationship between certain agents and RCC may be modified by particular variants in xenobiotic metabolism genes.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 915.
Abstract 917: Polymorphic analysis of MUC4 minisatellites and its relation to cancer
Authors: Lee Se-Ra , Yoon Se-Lyun , Ahn Myoung-Hyun , Chu In-Sun , Leem Sun-Hee
Published: February 2011

The membrane-bound mucins belong to O-glycoproteins family and they are thought to play important biological roles in cell-cell and cell-matrix interactions, in cell signalling and in modulating biological properties of cancer cells. Among them, MUC4 is well characterized and their altered expression in cancer indicates an important role for these membrane-bound mucins in tumour progression and metastasis; however, their genomic levels are unclear because of complex genomic properties. In this study, we identified seven novel minisatellites from the entire MUC4 region and investigated how allelic variation in these minisatellites may affect susceptibility to cancers. We analyzed genomic DNA from the blood of normal healthy individuals and five (MUC4-MS2, MS3, MS4, MS6, MS7) among the seven minisatellites exhibited polymorphism. Furthermore, a case-control study was performed that compared genomic DNA from 351 cancer-free controls with DNA from individuals with 352 gastric cancers. A statistically significant association was identified between long alleles of MUC4-MS3 and the odds of gastric cancer: odds ratio (OR), 1.3; 95% confidence interval (CI), 1.02-1.59; and p = 0.03. Moreover, MUC4-MS3 alleles showed the highest heterozygosity (h = 0.74) among seven minisatellites that may play a role in its chromosomal instability. This idea was examined by comparing the polymorphic alleles of hypervariable MUC4-MS3 minisatellites in the blood and cancer tissues from 36 patients with gastric cancer and 27 patients with liver cancer. The frequency of rearrangement in MUC4-MS3 was shown each as 27% and 11% in gastric and liver cancer tissues. Furthermore, these rearrangements were detected significantly higher in long alleles than in short alleles. These observations suggest that the long MUC4-MS3 alleles could function as identifiers for risk of gastric cancer. Additionally, we suggest that minisatellite instability might be associated with MUC4 function in cancer cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 917.