bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of bilateral oophorectomy on contralateral breast cancer risk in BRCA negative women from site-specific hereditary breast cancer kindreds.
Authors: Long Kara C , Pike Malcolm C , Otegbeye Ebunoluwa , Arnold Angela G. , Stadler Zsofia Kinga , Robson Mark E. , Barakat Richard R. , Offit Kenneth , Chi Dennis , Kauff Noah D. 
Published: March 2020

1511 Background: BRCA negative (BRCAneg) women from site-specific hereditary breast cancer (SSB) kindreds have been shown to have an increased risk of breast cancer (BC), but not ovarian cancer (OC). It is hypothesized that, as in women with BRCA mutations, bilateral salpingo-oophorectomy (BSO) will decrease the risk of developing future BCs in women from these BRCAneg SSB kindreds. Methods: Since 5/1995, all women undergoing genetic counseling and testing for BRCA mutations at our institution were offered participation in an IRB-approved prospective cohort study. This sub-study examines the impact of BSO on contralateral BC risk in BRCAneg SSB kindreds. Inclusion criteria were: a personal history of unilateral invasive BC ≤ age 60, at least one 1st or 2nd degree female relative with BC ≤ age 60, testing BRCAneg between 1/1/2002 and 2/28/2011. Exclusion criteria were: bilateral mastectomy (BM) or BSO prior to genetic testing, family history of OC, <6 months of followup (F/U). Demographic data and pedigrees were collected at the start of F/U, which was defined as the date of genetic testing. F/U data was obtained via mailed questionnaire and medical record review. Participants were censored at the time of BM, OC, or last F/U. Data were analyzed using a Cox proportional-hazards model with time from genetic testing as the time variable and BSO as the time dependent covariate. Results: 328 living participants met the inclusion criteria and F/U was obtained on 301 (208 via questionnaire, 93 via record review). Median age at genetic testing was 49.0 years (27.4-73.2 years). Median F/U time was 5.1 years (0.5-10.5 years). During the course of F/U, 43 women underwent BSO and 21 women underwent BM. There were 12 contralateral BCs (8 invasive, 4 DCIS) identified: 3 in the BSO group and 9 in the no-BSO group. After controlling for age, parity, prior hormone use, and estrogen receptor status of the original BC, the risk of contralateral BCs was not decreased in women who underwent BSO vs those who did not (HR 2.07, 95% CI 0.51 – 8.35, P=0.31). Conclusions: In BRCAneg women from SSB kindreds with a personal history of early onset BC, BSO does not decrease the risk of developing contralateral BC.
The role of statins for primary prevention in non-elderly colorectal cancer patients.
Authors: Sehdev Amikar , Shih Ya-Chen T. , Vekhter Benjamin , Lyttle Christopher , Polite Blase N. 
Published: March 2020

1513 Background: There is conflicting evidence for the effect of statins in primary prevention of colorectal cancer (CRC). We conducted a case control study (N=357,702) in non-elderly adult US population (age 18-64 years) to investigate the role of statins in primary prevention of CRC. Methods: We used MarketScan claims database to identify patients with CRC using ICD-9 codes. A case was defined as having an incident diagnosis of CRC. Up to ten controls (matched for age, sex, and geographical region) were selected per case. Statins exposure was assessed from prescriptions in the 12 months prior to the earliest date of CRC diagnosis. The primary objective was to assess the incidence of CRC in statin users and nonusers. Conditional logistic regression was used to adjust for multiple potential confounders and calculate adjusted odds ratios (AOR). Results: The mean age of CRC patients was 54 years, 52% were males.Statins were prescribed to 19.1% (68,461/357,702) patients.A total of 8.3% (5,704/68,461) patients developed CRC in statin exposed group compared to 9.3% (26,912/289,241) patients in non-statin exposed group. In a multivariate model, any statin use was associated with 25% reduced risk of CRC (AOR 0.75, 95% CI, 0.73-0.78, p<0.001). An age-stratified analysis showed more benefit in patients aged 55 years or less than those above age 56 years (AOR 0.68 and AOR 0.79 respectively; p<0.001 for interaction between age group and statin exposure). Variables associated with increased incidence of CRC in the multivariate model were obesity (AOR 1.3, 95% CI, 1.2-1.4, p<0.001); DM (AOR 1.2, 95% CI, 1.1-1.2, p<0.001); IBD (AOR 3.1, 95% CI, 2.8-3.5, p<0.001); use of insulin (AOR 1.2, 95% CI, 1.1-1.3, p<0.001) and sulfonylureas (AOR 1.2, 95% CI, 1.1-1.3, p<0.001). Prescribed NSAIDs showed modest reduction in CRC incidence (AOR 0.94, 95% CI, 0.91-0.97, p=0.002). There was no significant relationship between CRC incidence and other oral hypoglycemic drugs. Conclusions: Statins appears to reduce the incidence of CRC in non-elderly adult US population. A randomized controlled trial is needed to validate this finding.
Variation in the efficacy of low-dose computed tomographic lung screening based on risk of lung cancer mortality in the National Lung Screening Trial.
Authors: Katki Hormuzd A. , Kovalchik Stephanie A , Tammemagi Martin , Berg Christine D. , Caporaso Neil , Riley Tom , Korch Mary , Silvestri Gerard A. , Chaturvedi Anil 
Published: March 2020

1523 Background: Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the National Lung Screening Trial (NLST). The efficacy of LDCT screening could be improved by targeting smokers at highest risk of lung cancer death, provided that the efficacy of LDCT screening increases with lung cancer mortality risk. Methods: We evaluated the efficacy of LDCT screening as compared to chest radiography in the NLST across groups defined by participants’ 5-year risk of lung cancer mortality at randomization, which was estimated using a validated prediction model. Across quintiles of 5-year lung cancer mortality risk [Q1: 0.15%-0.55%, Q2: 0.56%-0.84%, Q3: 0.85%-1.24%, Q4: 1.24%-2.0%, Q5: >2.0%], we estimated the number of participants with false positive screens, the number of prevented lung cancer deaths, and their ratio. Results: The number of prevented lung cancer deaths due to LDCT screening increased in tandem with lung cancer mortality risk (Q1=0.2, Q2=3.5, Q3=5.1, Q4=11.0, Q5=12.0 per 10,000 person-years; P-trend=0.01). The number of participants with false positive screens per lung cancer death prevented, a measure of screening efficiency, significantly decreased with increasing risk (Q1=1,648, Q2=181, Q3=147, Q4=64, Q5=65, P-trend<0.001). The 60% of participants at highest 5-year lung cancer mortality risk (0.85% or greater) accounted for 88% of LDCT-preventable lung cancer deaths and included only 64% of participants with a false positive screen. The 20% of participants at lowest lung cancer mortality risk (0.15%-0.55%) accounted for only 1% of LDCT-preventable lung cancer deaths. Conclusions: In the NLST, LDCT screening prevented the most lung cancer mortality among those at highest lung cancer mortality risk and prevented almost no mortality among those at lowest risk, providing empirical support for risk-based targeting of smokers to improve the efficacy of LDCT screening.
Smoking and estrogen plus progestin (E+P) and lung cancer incidence and mortality.
Authors: Chlebowski Rowan T. , Wakelee Heather A. , Rohan Thomas E , Liu Jingmin , Simon Michael S. , Tindle Hilary , Messina Catherine R , Wactawski-Wende Jean , Johnson Karen , Schwartz Ann G. , Gass Margery 
Published: March 2020

1524 Background: In the Women’s Health Initiative (WHI) randomized, placebo-controlled clinical trial, E+P increased deaths from lung cancer (those cancer-attributed) and after lung cancer (regardless of cause) (Lancet 2009:374:1243). To examine smoking status influence on this process, a cohort combining WHI clinical trial (CT) and observational study (OS) participants, the latter meeting criteria as in the CT, was identified to examine E+P associations with lung cancer incidence and outcome. Methods: 31,966 postmenopausal women (12,299 CT, 19,668 OS) with no prior hysterectomy and no prior hormone therapy use were classified at baseline as not hormone users or E+P users and as current or never smokers. Lung cancers were verified by medical record review. Multi-variant adjusted Cox proportional hazards regression, including pack-year use, calculated hazard ratios (HRs, 95% confidence intervals [CI]) for groups defined by smoking status and E+P use for lung cancer incidence, deaths from lung cancer and deaths after lung cancer. Results: After 12 years mean follow-up, 664 lung cancers were diagnosed with 444 deaths from lung cancer and 513 deaths after lung cancer. Analyzed from cohort entry; see Table. In nonusers of E+P, lung cancer incidence, deaths from lung cancer, and deaths after lung cancer were significantly and substantially greater in current smokers vs never smokers (p< .0001 for all comparisons). In current smokers, lung cancer incidence, deaths from lung cancer and deaths after lung cancer were significantly and substantially greater in E+P users vs non-users (p=.0021, .0005 and .0002, respectively). Conclusions: E+P use in current smokers nearly doubles their already high risk of death from and after lung cancer. Based on this risk, current smokers should not use E+P. [Table: see text]
Cancer risks and mutation spectrum of mismatch repair genes in African American families with Lynch syndrome.
Authors: Kupfer Sonia , Guindalini Rodrigo Santa Cruz , Gulden Cassandra , Ukaegbu Chinedu I , Koeppe Erika , Conrad Peggy , Hampel Heather , Stoffel Elena Martinez , Syngal Sapna , Olopade Olufunmilayo I. 
Published: March 2020

1530 Background: Although African Americans (AA) have the highest colorectal cancer (CRC) incidence and mortality of all populations in the United States, no studies have determined cancer risk and mismatch repair (MMR) genes mutation spectrum in LS patients of AA ancestry and the contribution of this syndrome to cancer disparities. Thus, the aims of this study are: (1) to describe LS cancers in AAs; (2) to investigate the mismatch repair (MMR) gene mutation spectrum in AA families with LS; (3) to determine how Amsterdam II criteria, revised Bethesda guideline, and PREMM(1,2,6) model perform for predicting MMR gene mutations in this population. Methods: Pedigrees of AA families with deleterious mutation or suspected deleterious mutation in MMR genes from five US referral centers were analyzed for personal and familial clinical cancer histories. Results: Twenty-four AA families were identified, of which 22 had deleterious mutations (15 MLH1, 4 MSH2, 2 MSH6, 1 PMS2) and 2 had suspected deleterious mutations (1 MLH1, 1 MSH2). Three recurrent mutation were found in MLH1(677G>A, IVS1-2A>G, IVS4-1G>A), accounting for 25% of all mutations. Of 24 probands, 58% were female and 96% had personal history of cancer. The median age at first primary tumor was 42yrs (range 28-57) and 50% developed more than 1 primary tumor. The majority of probands (79%) had CRC (median age of onset – 42yrs [range 31-61]), of which 26% had at least 2 CRC primaries. Endometrial cancer developed in 50% of the women (median age of onset – 51yrs [range 32-57]). Amsterdam II and Bethesda criteria were met in 63% and 88% of the individuals, respectively. Median score by PREMM(1,2,6) model was 54% (range 12.9-99.8). Conclusions: To our knowledge, this is the largest series of AA families with LS reported to date. Earlier age of onset for CRC at 42yrs (previously reported ~45 yrs) is suggested. The majority of mutations were found in MLH1 (67%), including three recurrent mutations. A 10% cutoff for PREMM(1,2,6) predictive model identified all mutation carriers. Larger studies are warranted to confirm the differences observed in age of CRC onset in this population.
A prospective comparison study on EGFR mutations by direct sequencing and ARMS in completely resected Chinese non-small cell lung cancer with adenocarcinoma histology (ICAN).
Authors: Zhang Xuchao , Wu Yi Long , Wang Jun , Chu Xiang-Yang , Liu Zhi-Dong , Shen Yi , Ma Haitao , Fu Xiang-Ning , HU Jian , Zhou Nai-Kang , Liu Yongyu , Zhou Xinming , Wang Jian-Jun , Yang Kang , Xu Lin , Li Jian , Wang Si-Yu , Wang Qun , Liu Lun-Xu , Xu Shun 
Published: March 2020

1547 Background: ICAN study investigated EGFR mutation (M) status, clinical outcomes and recurrent risk factors in Chinese lung adenocarcinoma (ADC) patients (pts) after complete resection. Here we report analysis results for the overall EGFR M rate and the consistency between two EGFR M detecting methods, ARMS and PCR+direct sequencing (Seq). Methods: Pts were aged ≥18 years, with histological diagnosed lung ADC, and received surgical complete resection. Tumor sample EGFR M status (primary endpoint; positive [M+]) was determined according to clinical routine practice by whatever methods, including ARMS, Seq, liquid chip and mutant-enriched PCR. For the pts whose tissue was adequate after EGFR M testing by single method of either ARMS or Seq, the other method was applied. Results: Of 571 pts from 26 sites, 315 (55.2%) pts were EGFR M+. 420 pts’ tissues were tested by both ARMS and Seq. EGFR M+ rates were 58.1% and 54.5% respectively without statistical significance (p=0.0548). The total consistent rate (both M status and M types) between two methods was 76.7%. The following Table showed individual EGFR M types by two methods. Conclusions: The overall EGFR M+ rate in operable Chinese ADC was 55.2%. For resection samples, two common methods, ARMS and Seq, didn’t show statistical significance on EGFR M+ rate. Regarding EGFR M types, Seq found some rare mutations which ARMS kit could not detect, while ARMS seemed more sensitive for exon 20 and 21 mutations, especially for S768I and L861Q. Clinical trial information: NCT01106781. [Table: see text]
Decreased TGFBR1 signaling and breast cancer.
Authors: Henegan Clark , Moore-Smith Lakisha , Yi Nengjun , Ahsan Habibul , Whittemore Alice S , Pasche Boris 
Published: March 2020

1548 Background: We previously identified TGFBR1*6A (rs11466445), a hypomorphic TGF-beta type 1 receptor variant that is associated with cancer risk, has impaired TGF-beta signaling capability, and enhances the migration and invasion of breast cancer cells (Cancer Res 2008, 68:1319). Two recent large meta-analyses of case control studies have found a significant association between TGFBR1*6A and risk of breast cancer (Mol Biol Rep 2010 37:3227; PLoS One 2012,7(8). Rs7034462 is a single nucleotide polymorphism (SNP) in a noncoding region more than 9 kilobases upstream of TGFBR1 exon 1, which has been shown to be associated with decreased TGFBR1 expression similar to TGFBR1*6A (J Exp Clin Cancer Res 2010, 29:57). In this study we tested the hypothesis that rs7034462 may be associated with breast cancer risk. Methods: rs7034462 was genotyped in DNA obtained from patients with breast cancer and their unaffected sisters recruited by the Breast Cancer Family Registry (B-CFR). Results: The median age of cases and controls was 48.8 and 47.6 years, respectively. Using a simple case-control genetic association analysis for this family-matched population, rs7034462 was found to be associated with breast cancer risk. Conclusions: TGFBR1 rs7034462 is emerging as a low penetrance breast cancer susceptibility allele suggesting that two distinct TGFBR1 SNPs, each associated with decreased TGFBR1 expression, may modulate breast cancer risk. [Table: see text]
The first 10 years experience with genetic testing (GT) for BRCA1/2 mutations in a publicly funded program at a tertiary care teaching hospital in Ontario, Canada.
Authors: Ruste Sherry Athena Doroja , Eisen Andrea , Pritchard Kathleen I. 
Published: March 2020

1550 Background: Publicly funded testing for BRCA1/2 mutations in Ontario has been available for high-risk individuals since 2000. The criteria are based on personal and/or family cancer history and ethnicity. We reviewed the results of the first 10 yrs of testing at our institution, a regional cancer centre in an academic, tertiary care teaching hospital. Methods: This REB-approved, retrospective study included individuals who had GT from 2001-2011. Sociodemographic, clinical, and GT results were collected. Results: 2,305 individuals met criteria and underwent GT between Jan. 2001and Dec. 2011. Of all tested subjects, 93% were female, median age was 55 yrs., 23% were of Ashkenazi Jewish (AJ) ancestry and 80% lived in an area with family income $50-100K/yr. BRCA1/2 mutations were present in 16%, 8% had unclassified variant (UCV), 76% had normal sequence. We excluded 460 individuals who had predictive GT for a familial mutation, and results are shown in the Table. For each carrier, an average of four additional relatives had GT. The most common criteria for GT was at least three cases of ovarian or breast cancer at any age on the same side of the family. BRCA mutations were most common among those AJ, Italian, Asian Oriental and English ancestry. Wait time for GT result improved from 107 wks. in 2001 to 8 wks. in 2011. Conclusions: In our tested population, the prevalenceof BRCA1/2 mutations was high. Over time wait times improved and more relatives were tested. [Table: see text]
Differences in outcome between colorectal cancer (CRC) patients (pts) with Lynch syndrome (LS) versus MLH1 hypermethylation (MLH1 HM).
Authors: Haraldsdottir Sigurdis , Wu Christina Sing-Ying , Pan Xueliang Jeff , Hampel Heather , Goldberg Richard M. , Bekaii-Saab Tanios S. 
Published: March 2020

1556 Background: In ~15% of CRC tumors mismatch repair deficiency (dMMR) is observed and is usually caused by LS (germline mutations in MLH1, MSH2, MSH6 or PMS2) or sporadic inactivation of MLH1 (hypermethylation [HM] of MLH1 gene promoter). The objective of this study was to retrospectively compare clinical factors and outcomes in pts with dMMR with LS to those without LS. Methods: This cohort includes pts with CRC diagnosed between 5/98 and 5/12 with dMMR on immunohistochemistry (IHC) staining. Prior to 2006 pts came from the Columbus area HNPCC study. After 2006, we included all CRC pts at OSU as universal IHC was initiated. Chi-square was used to compare nominal parameters and log-rank to compare overall survival (OS). Results: A total of 189 pts had dMMR per IHC staining (see characteristics in table). In 36 pts (19.0%) a diagnosis of LS was made after germline testing, in 59 pts (31.2%) a diagnosis of MLH1 HM was made with methylation or BRAF testing, in 65 pts (34.4%) a LS or MLH1 HM diagnosis was assumed based on clinical criteria. Median OS was 159 mos in the LS group and 49 mos in the MLH1MH group (p=0.003) and OS was significantly longer in the LS group across all 4 stages (p=0.002) (see Table). Conclusions: Pts with LS-associated CRC had longer OS than pts with MLH1 HM-associated CRC, even in the setting of a higher incidence of other cancers (44.1% vs. 28%). This is likely related to younger age in the LS group. The MLH1HM group was older at diagnosis and more often female. There are a number of limitations to our study including the potential for survivorship bias and lack of a definitive diagnosis in ~50% of patients despite using clinical criteria to define these pts. [Table: see text]
Prostate cancer screening: Rise and fall?
Authors: Eisinger François , Morere Jean Francois , Touboul Chantal , Pivot Xavier B. , Coscas Yvan , Blay Jean-Yves , Lhomel Christine , Viguier Jérôme 
Published: March 2020

1562 Background: Our previously published data showed a fast increasing rate of prostate cancer screening in men aged 50-74 from 36% in 2005 to 48% in 2008. According to their expressed wish either to continue to be tested annually or to start prostate cancer screening, the rate of testing was expected to rise to 70% in 2011. We report here the actual rate of prostate cancer screening. Methods: Three nationwide observational surveys (EDIFICE opinion polls) were carried out by telephone (2005, 2008, and 2011). The target was a representative sample of more than 1,500 subjects living in France and aged 40-74. Precision of results for the samples was + 3.2% with a 95% confidence interval (CI). Results: In this survey population (men aged 50-74), the rate of screening reported remained stable between 2008 and 2011 (48% and 49% respectively). However, there were some differences according to age with a decreasing rate for men aged 50 to 59 years: 44% in 2008 vs 37% in 2011 (p=0.11) and an increasing rate for men aged 60 to 74 years: 53% in 2008 vs 62% in 2011 (p=0.04). Comparing privileged versus underserved populations, significant differences were found with a relative decrease in attendance of those of higher professional status (p=0.034) and from higher income groups (p=0.015); the difference was not significant for educational attainment (p=0.147). For household with a monthly income above 2500 €, the screening rate decreased from 61% in 2008 to 51% in 2011, while for an income below 2500 €, the rate increased from 36% in 2008 to 44% in 2011. Conclusions: A plateau or even reduction in prostate cancer screening is observed, possibly due to a progressive recognition of the controversy on prostate cancer screening by the population, which previously engaged only the experts. After previously being more likely to take up prostate cancer screening, the backlash is mainly observed in the younger, wealthier groups. This “fall”, according to many health agencies should not be seen as a health threat. Health institutions and medical practitioners should, however, be aware of this trend, to avoid general mistrust of cancer screening as a whole.
Racial differences in perceived risk in participants enrolled in the American College of Radiology (ACRIN-6654) arm of the National Lung Screening Trial (NLST).
Authors: Lathan Christopher , Kumar Pallavi , Gareen Ilana F , Gorelick Jeremy , Sicks JoRean , Hyland Kelly , Park Elyse R. 
Published: March 2020

1563 Background: Blacks in the U.S. have higher incidence and mortality rates of lung cancer (LC) compared to whites. Previous work in small studies suggests that blacks have lower perceived risk of LC which may influence smoking cessation behavior. However, racial disparities in risk perceptions (RP) of LC and smoking related diseases (SRD) in heavy smokers have not been studied. We examined LC and SRD risk perceptions among black and white ACRIN NLST participants. Methods: The 10-item Smoking Risk Perceptions Scale (SRPS) for LC and SRD was administered to NLST participants, from 4 ACRIN sites, with a minimum 30 pack-year smoking history at 1 year following baseline screening chest x-ray or low dose computerized tomography (LDCT). We 1) validated the SRPS in black and white participants separately using exploratory and confirmatory factor analyses, 2) used 2-way ANOVAs to compare RP of black and white participants and 3) used multivariable linear regression models to identify factors associated with RP. Results: Among 1742 white and 194 black participants, the 10 SRPS items loaded onto two factors (absolute and relative risk; Cronbach’s alpha=0.92 and 0.95 for white and black participants, respectively). Black participants had significantly lower RP compared to white participants (SRPS range= 10-50, mean diff. 3.48, 95% CI 2.29-4.68, p<0.01). Factors significantly associated with lower RP in a multivariate linear regression were black race (β=4.59, p < 0.001), former smoking status (β=3.82, p<0.001), male gender (β=1.35, p<0.001), lower education (β=1.16, p =0.010), and older age (years, β = 0.15, p<0.001). Conclusions: We validated the SRPS in black and white ACRIN-6654/NLST participants. Blacks had significantly lower perceptions of LC and SRD risk compared to whites, even after adjusting for study arm, sociodemographics, and smoking status. Sociodemographic factors and smoking status were independently associated with lower RP. These findings confirm that black current and former smokers are at risk of underestimating their smoking-related risk, which may contribute to lower rates of adherence to screening and smoking cessation recommendations.