Citations

Abstract Using data from patients with invasive epithelial ovarian cancer, we sought to examine whether overall survival was associated with common inherited variation in candidate genes and genomic regions including those involved in angiogenesis, mitosis, and regions of interest from genome-wide association and expression studies. We conducted a two-stage analysis based on Mayo Clinic patients with replication of peak results in the Cancer Genome Atlas (TCGA). Ovarian cancer patients (N=312) seen at the Mayo Clinic diagnosed from 1999 to 2006 with median follow-up of 3.7 years (range, 0.1 − 9.5 years) and 172 observed deaths were analyzed at 993 single nucleotide polymorphisms (SNPs) in 179 genes. For all patients and for serous patients only (N=192 with 129 observed deaths), Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for each SNP, adjusted for other prognostic factors. Twenty-nine SNPs in ten genes revealed p < 0.01 among all cases or among serous cases only, including 21 independent SNP at r2=0.9; analyses within four genes (HGF, PLG, PRKACB, and DCTN5) yielded p < 0.001. The strongest result was in HGF at rs1800793 (all cases: HR 1.7, 95% CI 1.3 − 2.2, p-trend 1.9 E-5; serous cases: HR 1.6, 95% CI 1.2 − 2.2, p-trend 1.8 E-3). A correlated SNP rs2214825 also showed association (r2=0.76; all cases: HR 1.4, 95% CI 1.1 − 1.8, p-trend 3.3 E-3; serous cases: HR 1.4, 95% CI 1.0 − 1.9, p-trend 0.03), and PCA gene-level tests of the HGF locus were also significantly associated with survival (all cases, p=3.7 E-4; serous cases, p=0.01). Among all cases, differential survival was also associated with DCTN5 rs12447304 (HR 1.8, 95% CI 1.3-2.6; p=7.1 E-4), and among serous cases, with PLG rs783173 (HR 1.6, 95% CI 1.2 − 2.0, p = 8.1 E-4) and PRKACB rs1402694 (HR 1.7, 95% CI 1.3 − 2.2, p=3.2 E-4). We then examined SNPs in the most suggestive gene, HGF, using data from TCGA which had genotyped four overlapping HGF SNPs in 350 invasive cases (188 deaths). Covariate-adjusted TCGA analysis at rs2214825 revealed consistent results (HR 1.7, 95% CI 1.3-2.2, p=1.4 E-4) as did analyses of three other HGF SNPs (HR range 1.3 to 1.5, p range 3.4 E-3 to 0.049); correlation between SNP genotypes and HGF expression was also observed (p=1.4 E-3, rs2214825, probe 210997_at). While this is the first report of SNPs in HGF, it has long been known that the HGF signaling pathway, activated by HGF ligation of c-MET, plays a key role ovarian cancer cell growth, migration, and invasion. c-MET is overexpressed in 40%-60% of ovarian tumors, and high overexpression is associated with lower overall survival. In addition, HGF has been shown to enhance the response of ovarian cancer cells to low doses of paclitaxel and cisplatin by activating the intrinsic apoptotic pathway, leading to cancer cell death. These results now suggest that inherited differences in HGF among women with invasive disease may play a role in survival, holding potential clues for tailored avenues of treatment. 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 897.

Abstract Background: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. Methods and Findings: Women with and without invasive ovarian cancer (749 cases, 1,041 controls) were genotyped at 136 single nucleotide polymorphisms (SNPs) within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog) was associated with risk of serous cancer (p=0.03); haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog) were associated with risk of invasive disease (p=0.03). MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95% CI 0.66-0.98; p=0.03). SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p<0.05), and there was increased risk at HEXIM1 rs1053578 (p=0.04, OR 1.40, 95% CI 1.02-1.91). Conclusions: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasive serous ovarian 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 4718.

Background Telephone quitlines that provide counseling support are efficacious in helping cigarette smokers quit and have been widely disseminated; currently, they are underused. Surgery represents a teachable moment for smoking cessation, which can benefit surgical outcomes; however, few surgical patients receive smoking cessation interventions. This study developed and tested a clinician-delivered intervention to facilitate quitline use by adult patients scheduled for elective surgery. Methods After formative work involving patients and clinicians, a brief intervention was designed to facilitate telephone quitline use. It was then evaluated in a randomized trial of 300 adults scheduled for elective surgery. A control standard brief stop-smoking intervention served as a comparator, with both interventions delivered by clinicians. The primary outcome was the use rate of a quitline accessed through a dedicated toll-free telephone number, with use defined as completing at least one full counseling session. Secondary outcomes included self-reported abstinence from cigarettes at 30 and 90 days postoperatively. Results Subject characteristics were similar between the two groups. Records from the designated quitline documented that 29 of 149 subjects (19.5%) in the quitline intervention group and 0 of 151 subjects in the control group completed the first full counseling session (P < 0.0001). There were no significant differences in the self-reported point-prevalent and continuous abstinence rates between groups at either 30 or 90 days postoperatively, although rates tended to be higher in the quitline intervention group. Conclusions Clinicians can effectively facilitate quitline use by surgical patients. Further work is necessary to evaluate the efficacy of this approach in terms of long-term abstinence from cigarette smoking.

Abstract Pancreatic cancer is a devastating disease for which the role of dietary risk factors remains inconclusive. We evaluated fruit, vegetable, fiber, and grain consumption with pancreatic cancer risk using a clinic-based case-control design, excluding participants who reported changing their diet within 5 years prior to entering the study. Our study included 384 rapidly ascertained cases and 983 non-cases (frequency matched on age at time of recruitment (± 5 years), race, sex, and region of residence) who completed epidemiologic surveys and a 144-item food frequency questionnaire developed by the National Cancer Institute. Logistic regression was used to calculate odds ratios (OR) and 95% CIs, adjusted for age, sex, smoking, body mass index, energy intake, and alcohol consumption. Comparing highest to lowest quintiles, we observed significant (OR &lt; 0.01) inverse associations with significant trends (ptrend &lt; 0.01) for citrus, melon, and berries, other fruit, dark green vegetables, deep yellow vegetables, tomato, other vegetables, dry bean and pea, insoluble fiber, soluble fiber, and whole grains. Adjusting for diabetes or total sugar intake in the multivariate logistic regression model did not significantly affect results. Consuming a diet high in fruits, vegetables, fiber, and whole grains may reduce the risk of developing pancreatic cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A85.

Physicians are often unable to guide patients through the advance care planning (ACP) process due to cost and time constraints. We conducted a retrospective analysis in the primary care setting targeting older adults without an advance medical directive (AMD). An ACP educational packet was sent to intervention patients before their health maintenance examination (HME). Additionally, their physicians had access to a computerized clinical decision support system on AMD completion at the time of the HME. Control participants’ physicians had access to the computerized decision support system and traditional resources only. All participants who received the packet were sent a follow-up survey. In all, 21.6% of intervention participants completed an AMD, compared with 4.1% of control participants. Combining clinical decision support systems and standardized processes enhances the ACP process.

AbstractObesity is a controversial risk factor for colorectal cancer (CRC) in older women. We evaluated associations between multiple body size parameters and incident CRC in the prospective, population-based Iowa Women's Health Study (IWHS). IWHS participants, ages 55 to 69 years, provided data regarding height; weight; weight at ages 50, 40, 30, 18 years; hip circumference; and waist circumference at baseline (1986). Derived variables included body mass index (BMI), waist-to-hip ratio (WHR), and “overweight years” (OWY; conceptually similar to cigarette pack-years). Incident CRC cases (n = 1,464) were ascertained from the State Health Registry of Iowa, through 2005. Multivariable Cox regression models were fit to estimate body size–associated CRC risks. Among 36,941 women (619,961 person-years), baseline height, weight, BMI, hip circumference, waist circumference, and WHR were all positively associated with incident CRC (Ptrend ≤ 0.003 for each). Baseline BMI yielded the highest CRC risk estimates (obese III versus normal, RR = 1.56; 95% CI = 1.10–2.22; Ptrend &lt; 0.001) and was more closely associated with distal than proximal tumors (Ptrend &lt; 0.001 versus 0.06). Conversely, height was more closely associated with proximal than distal tumors (Ptrend &lt; 0.001 versus 0.04). Other body size parameters were less predictive of incident CRC. These data strongly support a positive association between increased body size and CRC risk among older women. Further investigation of when increased body size has the greatest effect on CRC risk (i.e., early adulthood versus later adulthood) might also be informative, particularly with respect to defining subsite-specific pathways of colorectal carcinogenesis. Cancer Prev Res; 3(12); 1608–20. ©2010 AACR.

Potential donors with congenital renal anomalies but normal renal function are often overlooked because of a possible increase in technical difficulty and complications associated with the surgery. However, as the waiting list for a deceased donor kidney transplant continues to grow, it is important to consider these kidneys for potential transplant. This paper describes the procurement of a crossed fused ectopic kidney, and subsequent parenchymal transection prior to transplantation as part of a combined simultaneous kidney pancreas transplant. The transplant was uncomplicated, and the graft had immediate function. The patient is now two years from transplant with excellent function.

Purpose This study’s main purpose was to (a) identify acoustic signatures of hypokinetic dysarthria (HKD) that are robust to phonetic variation in conversational speech and (b) determine specific characteristics of the variability associated with HKD. Method Twenty healthy control (HC) participants and 20 participants with HKD associated with idiopathic Parkinson’s disease (PD) repeated 3 isolated sentences (controlled phonetic content) and 2 min of conversational speech (phonetic content treated as a random variable). A MATLAB-based program automatically calculated measures of contrastivity: speech–pause ratio, intensity variation, median and maximum formant slope, formant range, change in the upper and lower spectral envelope, and range of the spectral envelope. t tests were used to identify which measures were sensitive to HKD and which measures differed by task. Discriminant analysis was used to identify the combination of measures that best predicted HKD, and this analysis was then used as a general measure of contrastivity (Contrastivity Index). Differential effects of HKD on maximum and typical contrastivity levels were tested with interaction of maximum, minimum, and median observations of individual speakers and with pairwise comparisons of skewness and kurtosis of the contrastivity index distributions. Results Group differences were detected with pairwise comparisons with t tests in 8 of the 9 measures. Percentage pause time and spectral range were identified as the most specific (95%) and accurate (95%) differentiators of HKD and HC conversational speech. Sentence repetition elicited significantly higher levels of contrastivity than conversational speech in both HC and HKD speakers. Maximum and minimum contrastivities were significantly lower in HKD speech, but there was no evidence that HKD affects maximum contrastivity levels more than median contrastivity levels. The HKD speakers' contrastivity distributions were significantly more skewed to lower levels of production. Conclusion HKD can be consistently distinguished from HC speech in both sentence repetition and conversational speech on the basis of intensity variation and spectral range. Although speakers with HKD were effectively able to produce higher contrastivity levels in sentence repetition tasks, they habitually performed closer to the lower end of their production ranges.

Background Tightness of the posteroinferior capsule is assumed to be the cause of internal rotation loss in baseball pitchers. Although the relationship between posterior capsule and subacromial impingement has been recognized, this relationship during the baseball-pitching motion is unclear. Hypothesis Contact pressure during baseball-pitching motion increases with posterior capsule tightness. Study Design Controlled laboratory study. Methods Eight fresh-frozen shoulders were used. The peak contact pressure and area on the coracoacromial arch were measured on a custom-designed shoulder experimental device capable of 6 degrees of freedom motion. Simultaneously, the sites of peak pressure on the coracoacromial arch and humerus were observed from various angles. The posteroinferior capsule tightness was simulated by plicating the capsule in the region from 6 to 8 o'clock. The static testing positions correlated to the early cocking, late cocking, acceleration, deceleration, and follow-through phases of the pitching motion. Results The peak contact pressure during the follow-through phase (0.63 ± 0.50 MPa) significantly increased with posteroinferior capsule tightness (1.00 ± 0.65 MPa) (P = .014). Additionally, the contact area on the coracoacromial ligament during the follow-through phase (0.98 ± 0.67 cm2) significantly increased with posteroinferior capsule tightness (1.47 ± 0.91 cm 2) (P < .001). The site of the peak contact pressure did not change between the 2 conditions. Conclusion Our findings demonstrate that posteroinferior capsule tightness leads to higher contact pressure under the subacromial arch and increased contact area, particularly on the coracoacromial ligament during the follow-through phase. Clinical Relevance This tightness may affect risk of injury of the rotator cuff and its surrounding tissues by increasing subacromial contact during pitching.