bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic sequence variant (GSV) in TERT-CLPTM1L (5p15.33 locus) and survival in platinum-treated stage-IV non-small cell lung cancer (NSCLC).
Authors: Azad Abul Kalam , Qiu Xiaoping , Cuffe Sinead , Qiu Xin , Boyd Kevin , Kuang Qin , Emami Marjan , Perera Nicole , Palepu Prakruthi R. , Patel Devalben , Chen Zhuo , Cheng Dangxiao , Feld Ronald , Leighl Natasha B. , Shepherd Frances A. , Tsao Ming Sound , Xu Wei , Liu Geoffrey 
Published: March 2020

1535 Background: Lung cancer is a leading cause of cancer-related mortality in North America. Besides tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether GSVs associated with lung cancer risk are also associated with overall survival (OS) and progress free survival (PFS) in platinum-treated stage-IV NSCLC patients. We chose this subset of patients with lung cancer because they are uniformly treated and followed up at our institute (Princess Margaret Hospital). Methods: A total of 32 candidate GSVs in 21 genes previously reported to be associated with lung cancer risk were genotyped in 188 platinum-treated NSCLC stage-IV patients. Illumina Custom GoldenGate Genotyping Panel was used for the genotyping assay platform. Multivariate Cox proportional hazard models adjusted for the potential clinical prognostic factors were generated for OS and PFS. Results: Median age is 60 yr (range: 31-81); 73% with adenocarcinoma. Median follow-up time is 27 mo; median OS is 16 mo and PFS is 8 mo. The top significant GSV was rs4975616 (g.1315660G>A) in telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) gene on chromosome 5p15.33. The adjusted hazard ratio (aHR) for OS was 0.76 (95% CI: 0.58-0.99; p=0.04) and for PFS aHR was 0.70 (95% CI: 0.55-0.90; p=0.005) for each protective allele, respectively. This GSV has previously been associated with lung cancer risk in genome-wide association study (PMID: 19654303). Conclusions: The TERT-CLPTM1L:rs4975616 GSV is not only a risk factor for lung cancer but also is associated with survival in patients with stage-IV NSCLC treated with platinum based chemotherapy. GSVs may be able to define subsets of patients with different risk and prognosis of NSCLC. Future studies should evaluate whether this GSV is predictive or prognostic.
Analysis of mutations in formalin-fixed paraffin-embedded (FFPE) tumor samples from two phase II clinical trials using a Sequenom-based approach.
Authors: Orr Maria , Sherwood James , McWalter Gael , Donald Emma 
Published: March 2020

1548 Background: Analysis of tumour samples for biomarker discovery, personalised health care and disease stratification is becoming increasingly important. Methods to detect somatic mutations are often limited by the requirement for a significant amount of input DNA, low sensitivity or low sample throughput. The aim of this work was to obtain a comprehensive mutation profile of tumour samples taken from patients enrolled on two Phase II clinical trials. A Sequenom based approach was used to determine mutation profiles for the samples so that these could be correlated with response at some future date. Methods: After successfully piloting the Sequenom MassArray 4 platform on formalin fixed paraffin embedded (FFPE) tumour samples and tumour cell line admixes, we ran an exploratory analysis of 177 melanoma and 230 non small cell lung cancer (NSCLC) FFPE samples collected from two phase II clinical trials. DNA was extracted from the FFPE samples using the QIAmp DNA FFPE Tissue Kit (Qiagen). We designed a panel of 86 assays in 14 genes covering approximately 160+ mutations. Mutations were chosen based on mutation frequency and biological significance in these tumour types. Results: Using this approach we were able to detect concomitant mutation profiles in a significant percentage of samples using only approximately 20uL of FFPE DNA (500 copies/µL average). Mutation status concordance was over 97% in BRAF and KRAS when compared to data generated via other approaches (sequencing, ARMS). Conclusions: Using Sequenom to screen tumour material, collected during clinical trials, is a feasible, rapid and comprehensive approach. Such an approach can be used to identify mutation profiles which correlate with patient response, potentially identify further patient stratification and help generate new hypotheses for further exploration.
NAD(P)H: Quinone oxidoreductase 1 (NQO1) C609T polymorphism and lung cancer risk: A meta-analysis.
Authors: Lou Yuqing , Li Rong , Xiong Liwen , Han Baohui 
Published: March 2020

1551 Background: No clear consensus has been reached on the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung cancer risk. We performed a meta-analysis to summarize the possible association. Methods: We conducted a computer retrieval of PUBMED and EMBASE databases prior to January 2012. References of retrieved articles were also screened. According to the inclusion criteria, 24 articles (31 studies) were finally included. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. Results: There was no statistical association between C609T polymorphism and lung cancer risk in overall, East Asians, African-Americans or Hispanics. In Caucasians, significant association was found in allele comparison model (T vs. C) (P=0.04, OR=1.09, 95%CI [1.00–1.19], Pheterogeneity=0.24, fixed-effects model). In Hawaiians, significant association could be found in dominant genetic model ((TT+CT) vs. CC) (P=0.04, OR=0.52, 95%CI [0.28–0.96], fixed-effects model). In the subgroup of squamous cell carcinoma, a borderline significance could be found in the dominant genetic model ((TT+CT) vs. CC) (P=0.05, OR=1.20, 95%CI [1.00–1.43], Pheterogeneity=0.65, fixed-effects model). Significant association could also be found in allele comparison (T vs. C) (P=0.03, OR=1.21, 95%CI [1.01–1.44], Pheterogeneity=0.68, fixed-effects model). In the subgroup of small cell lung cancer risk, significant association were found in allele comparison (T vs. C) (P=0.03, OR=1.68, 95%CI [1.05–2.68], Pheterogeneity=0.10, random-effects model) and in the homozygote comparison (TT vs. CC) (P=0.02, OR=2.79, 95%CI[1.14–6.85], Pheterogeneity=0.72, fixed-effects model). No association was observed in adenocarcinoma subgroup. Conclusions: NQO1 C609T polymorphism might associate with lung cancer risk in Caucasians and Hawaiians. NQO1 C609T polymorphism might also associate with squamous cell carcinoma and small cell lung cancer risk.
Differential effects of light at night and shift rotation pattern on the circadian system in night workers.
Authors: Razavi Pedram , Schernhammer Eva S ,   Nurses' Health Study II (NHS2) Group
Published: March 2020

1556 Background: Light at night as in shift work suppresses nocturnal secretion of melatonin, a pineal hormone with oncostatic properties. Several studies have associated night shift work with higher risk of cancer, leading WHO in 2007 to classify rotating night shift work as “probably carcinogenic”. We conducted one of the most comprehensive studies, to date, to evaluate the effects of light and night shift work on melatonin measurements in the field. Methods: Study participants were 130 active nurses (84 current rotating night shift workers and 46 day shift workers) participating in NHS2. Each nurse wore a head-mounted light- and accelerometer for a 3-day study period, during which each spontaneous urine was collected for repeated urinary 6-sulfatoxymelatonin (melatonin) measurements. In addition, nurses were asked to fill out paper questionnaires and diaries. We used mixed models to evaluate the influence of light, activity and night shift work on urinary melatonin level adjusting, for age, lifestyle, and occupational history. We log-transformed main variables and report geometric means (GM [standard deviation]). Results: Greater levels of light were associated with lower melatonin (P < 0.0001), independent of activity level. An increase in light intensity from 10 to 100 lux was associated with a 12% decrease in geometric mean of melatonin level; however, this inverse association was only significant at night (Ptrend = 0.01). At night, each hour increase in exposure to ≥ 20 lux light lowered melatonin level by 5.7% (Ptrend < 0.0001). A single night shift affected the circadian system by lowering melatonin peak by 22% (day shift: GM = 17.57 [2.73]; night shift: GM = 13.64 [2.54]) and induced a phase shift (PS) of 0.9 hours, -changes that reset to normal by the next day. Two consecutive night shifts had a similar effect as a single shift. However, the effect was worse after three consecutive night shifts (GM = 10.11 [2.77]; PS = 2.2 hours). Conclusions: We found significant inverse associations of intensity and duration of exposure to light at night with urinary melatonin, independent of activity level. Three consecutive night shifts affected the circadian system more strongly than two consecutive, or a single night shift.
Clinical and genetic predictors of weight gain in patients diagnosed with breast cancer.
Authors: Reddy Sangeetha Meda , Sadim Maureen , Helenowski Irene B. , Li Jun , Yi Nengjun , Kaklamani Virginia G. 
Published: March 2020

1561 Background: Obesity and weight gain in breast cancer patients has been associated with decreased quality of life, decreased response to chemotherapy, increased cancer recurrence, and higher all-cause mortality. Our study was designed to identify factors that contribute to this weight gain. Methods: Chart review was conducted on 565 breast cancer patients to obtain weights and BMIs over an 18 month period from diagnosis, tumor characteristics (ER/PR/Her2 status, grade, presence of LN metastases, stage), demographics (age, race), clinical factors (menopausal status), and treatment regimens (chemotherapy, hormone therapy, radiation). Blood samples were genotyped for polymorphisms in FTO (fat mass and obesity-associated protein) and the adiponectin pathway, two pathways found to be associated with obesity and breast cancer risk. Results: See table. For genetic analysis, one statistically significant epistatic and three gene x environmental interactions were detected for adiponectin SNPs: rs822396d x BMI at diagnosis (effect size 8.65), rs2232853a x age (2.75), rs1501299a x BMI at diagnosis (3.63), and rs266729d x rs7539542d (6.40). Conclusions: We have identified multiple clinical and genetic variables that are likely predictors of weight gain in breast cancer patients. We are conducting a prospective study of 200 breast cancer patients to validate the findings of this retrospective study. By identifying a high risk patient population, we hope to target them for aggressive lifestyle interventions to prevent weight gain and thereby improve their mortality and morbidity. [Table: see text]
Risk perception and knowledge of breast and colon cancers in a diverse population.
Authors: Lang Katherine , Gyure Maria , Rodriguez Vivian , Corona Rosalie , McClish Donna , Bowen Deborah , Krist Alex , Borzelleca Joseph , Bodurtha Joann , Quillin John 
Published: March 2020

1563 Background: The accuracy of cancer risk perception has implications for preventive behaviors. Studies show that despite receiving personalized breast and colon cancer risk information, people continue to overestimate their numeric risks. It is still not fully understood why this occurs. Breast cancer, especially, is highly visible in the media so an individual may hear more about breast cancer, increasing general knowledge but potentially inflating risk perceptions. This study explores relationships between general knowledge and numeric risk perceptions for breast cancer (BC) and colon cancer (CC) among women. We hypothesize that general knowledge of BC will be high relative to CC, but risk perception for BC will be less accurate. Methods: Data was obtained from the first 369 (final N=490) patients recruited for the Kin Fact study from a Women’s Health Clinic. Kin Fact is a randomized controlled trial examining effects of an intervention to increase cancer risk communication in families. Women complete baseline surveys including knowledge and numeric risk perception measures for BC and CC. We use CA Gene software to calculate actual lifetime risk for BC and CC. Correlations, t-tests and linear regressions were used for the analysis. Results: Women averaged 33 years old, and 58% were African American. Average lifetime risk was 3% for CC and 11% for BC. Women overestimated their numeric risk for both BC and CC, but the mean overestimation for BC (24%) was significantly larger than for CC (19%) (p<0.001). Average scores for BC knowledge were also significantly higher than for CC (p<0.001). Compared to knowledge about CC, women who had greater knowledge of BC also were more inaccurate in terms of their perceived numeric risk (r= -0.131, p=0.016). This finding remained significant controlling for age, race and genetic literacy. Conclusions: Results endorse an apparently paradoxical effect that compared with CC, women with increased knowledge of BC have less accurate risk perception for BC. Inaccuracies in perceived risk can affect psychosocial well-being and adherence to screening and prevention recommendations. Findings reveal a need for increasing knowledge about cancer without adversely impacting the accuracy of risk perceptions.
Esophageal cancer incidence gender disparity.
Authors: Mathieu Luckson Noe , Hooker Craig , Kanarek Norma , Rudin Charles M. , Brock Malcolm 
Published: March 2020

1573 Background: Over the past 30 years, esophageal cancer incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous and adenocarcinoma. The reasons for this gender difference and the possible role of estrogen are unclear. The objective of this study is to determine if estrogen exposure is consistent with the male predominance observed in esophageal cancer incidence. Methods: A database assessment of esophageal cancer incidence rates (age-adjusted) from 1975 to 2008 was conducted in the National SEER 9 Database and the Maryland Cancer Registry. Rates by gender and age were calculated. Gender-specific incidence rate ratios were compared across age groups. Annual percentage change (APC) was compared for each gender-age group. Results: In both national and state, male and female, adeno and squamous cell histologies, incidence rates increase with patient age. SEER data trends revealed the 50-64 aged female cohort as the only gender-age cohort APC decreasing between 1975-2008. Furthermore, a significant increase in incidence for females is observed in the 65+ age groups; whereas among males, the rates are rising in all age groups. Conclusions: Using age as a proxy for estrogen exposure, our findings suggest a hormonal component in the declining male: female esophageal cancer incidence rate ratios with increasing age and confirm gender differences in incidence long observed in esophageal cancer. Histological features may be predictive of a lower rate ratio. (Bodelon et al. 2011) Estrogen exposure may play a protective role in esophageal cancer which dissipates with time after age 60-69. Our data suggest possible future roles of estrogen as a chemopreventive agent in esophageal cancer (Barone et al. 2011). [Table: see text] [Table: see text]
Age, race/ethnicity, and the ER/PR/HER2 subtypes in breast cancer.
Authors: Parise Carol , Caggiano Vincent 
Published: March 2020

1582 Background: The association of age and ER/PR/HER2 subtype in African-American (AA) and Hispanic women with breast cancer has been reported. This study examines the association of age and subtype among 12 self-reported race/ethnicity categories. Methods: Using the California Cancer Registry 2000-2010, we examined 136,175 cases of first primary female invasive breast cancer. Race/ethnicity was stratified into 12 categories. The distribution of age and race/ethnicity among the 8 ER/PR/HER2 subtypes was examined. Age was stratified into <40, 40-69, and 70+ years. For each age strata, odds ratios (OR) and 95% confidence intervals (CI) were computed to assess the association of race/ethnicity with ER-/PR-/HER2+, ER-/PR-/HER2- (TN), and ER+/PR+/HER2+ (TP) when compared with the ER+/PR+/HER2- subtype. Results: The % of each race was: White 66.8; AA 6.0; Hispanic 15.9; Pacific Islander (PI) 0.3; Southeast Asian (SEA) 2.5; Indian Continent (IC) 0.7; American Indian; 0.2; Chinese 2.5; Japanese 1.2; Filipino 3.1; Korean 0.7; Hispanic/non-white 0.3. All AA women had increased ORs of the ER-/PR-/HER2+, TN and TP. Hispanic women mimicked the AA population except for young women with TP. Chinese (OR=0.53; 95%CI=0.37-0.76) Japanese (OR=0.51; 95%CI=0.28-0.96), and Filipino (OR=0.45; 95%CI=0.31-0.67) women <40 were less likely to have TN subtype. For women 40-69, SEA, Chinese, Filipino, and Korean women had increased ORs for TP, and ER-/PR-/HER2+. The Japanese had increased ORs for the TP (OR=1.23; 95%CI=1.00-1.49) but decreased odds for the TN (OR=0.72; 95%CI=0.57-0.90). IC women had increased odds for the TN (OR=1.38; 95%CI=1.10-1.72). Korean women 70+ were more likely to have the TP and ER-/PR-/HER2+. SEA had increased ORs for ER-/PR-/HER2+ and TN, IC only had increased ORs for TN (OR=2.03; 95%CI=1.26-3.27). Chinese and Filipino women only had increased ORs for the ER-/PR-/HER2+. Conclusions: AA and Hispanic women of all ages are at increased risk of the TN, and ER-/PR-/HER2+ subtypes. AA women of all ages and Hispanic women over age 40 are at increased risk of the TP subtype. The diversity of Asian women with regard to breast cancer necessitates accurately defining this population.
Correlation of high body mass index and circulating tumor cell positivity in patients with early-stage breast cancer.
Authors: Ortmann Uta , Janni Wolfgang , Andergassen Ulrich , Beck Thomas , Beckmann Matthias W. , Lichtenegger Werner , Neugebauer Julia Katharina , Salmen Jessica , Schindlbeck Christian , Schneeweiss Andreas , Scholz Christoph , Schreier Jörg , Spickhoff Frank , Zwingers Thomas , Rack Brigitte Kathrin 
Published: March 2020

1600^ Background: The prognostic relevance of both body mass index (BMI) and circulating tumor cells (CTC) has been confirmed in different trials for patients with early breast cancer. This analysis evaluates the correlation between high BMI and CTC positivity as risk factors for reduced disease free and overall survival. Methods: Data of 3658 patients of the SUCCESS A trial have been analyzed. CTC count and BMI were documented before (N = 2026) and after (N = 1504) chemotherapy. Within this trial patients with early breast cancer were randomized to two chemotherapy regimens and received either 3 cycles of fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel (FE100C-Doc) or 3 cycles of fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel and gemcitabine(FE100C-DG). In addition, patients were randomized to zoledronic acid either for 2 or 5 years. CTC were analyzed using the CellSearch System (Veridex, USA). Different groups of bodyweight were classified according to the WHO’s international definition: Underweight (BMI < 18,5 kg/m2), normal range (BMI > 18,5- < 25), overweight (BMI >25- < 30), obesity (BMI > 30). Correlation between CTC count and BMI was analyzed using frequency-table methods. Results: At study entry 24 (1.2%) patients were underweight, 952 (47%) patients were normal weight, 658 (32.5%) patients were overweight and 392 (19.4%) patients were obese. Before the start of chemotherapy, CTC were detected in 435 (21.5%) patients. We did not find a correlation between CTC positivity and BMI (p=0.94). After chemotherapy CTC were detected in 330 (16,3%) patients. Again, there was no statistically significant correlation between BMI and CTC positivity (p=0.86). In particular, CTC positivity was not observed more frequently in obese patients neither before (p=0.70) nor after chemotherapy (p=0.95) compared to patients with a BMI < 30 kg/m2. Conclusions: As compared to patients with normal BMI, there was no significant difference in the prevalence of CTC in underweight, overweight and obese patients, respectively, neither before nor after chemotherapy. The risk factors obesity and prevalence of CTC seem to be independent prognostic factors.
Correlation of BMI with tumor stage in early breast cancer patients (pts): Pooled analysis of the German SUCCESS A, B, and C trials.
Authors: Melcher Carola Anna , Ortmann Uta , Scholz Christoph , Zwingers Thomas , Schneeweiss Andreas , Lichtenegger Werner , Lorenz Ralf , Hagenbeck Carsten , Forstbauer Helmut , Ulmer Hans Ulrich , Kasprowicz Nikola S. , Heinrich Georg , Jaeger Bernadette Anna Sophia , Fehm Tanja N. , Beckmann Matthias W. , Janni Wolfgang , Rack Brigitte Kathrin 
Published: March 2020

1602 Background: Independent from known prognostic factors, e.g., tumor size and nodal status, obesity is a risk factor for poor disease free, distant disease free, and overall survival in breast cancer. The aim of this analysis was to examine the correlation of the body mass index (BMI) with tumor characteristics in early breast cancer. Methods: We analyzed the data of 7,997 pts with early, node positive or high risk node negative primary breast cancer treated with adjuvant taxan-based chemotherapy within the German multicenter phase III SUCCESS A, B, or C trials. The pts’ tumor stage at primary diagnosis was classified according to the UICC tumor-node-metastasis (TNM) classification. Additionally, the tumor’s hormone-receptor status and HER2/neu status were determined. Before enrollment into the study each patient was grouped according to the WHO global database on BMI. Contingency table methods were used to analyze the correlation of BMI and tumor characteristics. Results: Among the 7,997 pts 100 (1.3%) pts were underweight, 3,556 (44.5%) pts were normal weight, 2,569 (32.1%) pts were overweight and 1,772 (22.2%) were obese. Of all pts 4,508 pts (56.4%) suffered from a pT2-4 tumor, 4830 (60.4%) showed lymph node involvement (pN1-3) and 7509 (93.9%) had G2-3 tumors. 5839 pts (73.0%) showed positivity for ER or PR and 935 (11.7%) for HER2/neu. Overweight and obese pts had significantly larger tumors compared to pts with normal BMI (p<0.0001; p<0.0001). Furthermore, overweight and obesity were associated with a significantly higher rate of lymph node involvement (p=0.0001; p=0.0003) respectively. In contrast neither grading, tumor histology, ER/PR-status nor HER2/neu-overexpression were correlated with BMI. Conclusions: These data are the first to show in a large number of pts that both obese and overweight women suffering from primary breast cancer have significantly larger tumors and more often positive axillary lymph nodes. As there are no differences in tumor biology, the advanced tumor stage might be due to more difficult and delayed detection of breast cancer and lymph node lesions in these women.