Although dietary fibre has been reported to have no association with colorectal adenoma and cancer, in some studies this topic remains controversial.
We used a 137-item food frequency questionnaire ...to assess the relation of fibre intake and frequency of colorectal adenoma. The study was done within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomised controlled trial designed to investigate methods for early detection of cancer. In our analysis, we compared fibre intake of 33 971 participants who were sigmoidoscopy-negative for polyps, with 3591 cases with at least one histologically verified adenoma in the distal large bowel (ie, descending colon, sigmoid colon, or rectum). Odds ratios were estimated by logistic regression analysis.
High intakes of dietary fibre were associated with a lower risk of colorectal adenoma, after adjustment for potential dietary and non-dietary risk factors. Participants in the highest quintile of dietary fibre intake had a 27% (95% CI 14–38, p
trend=0·002) lower risk of adenoma than those in the lowest quintile. The inverse association was strongest for fibre from grains and cereals and from fruits. Risks were similar for advanced and non-advanced adenoma. Risk of rectal adenoma was not significantly associated with fibre intake.
Dietary fibre, particularly from grains, cereals, and fruits, was associated with decreased risk of distal colon adenoma.
High body mass index (BMI) has been associated with an increased risk for breast cancer among postmenopausal women. However, the relationship between BMI and breast cancer risk in premenopausal women ...has remained unclear. Data from two large prevention trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) were used to explore the relationship between baseline BMI and breast cancer risk. The analyses included 12,243 participants with 253 invasive breast cancer events from the Breast Cancer Prevention Trial (P-1) and 19,488 participants with 557 events from the Study of Tamoxifen and Raloxifene (STAR). Both studies enrolled high-risk women (Gail score ≥ 1.66) with no breast cancer history. Women in P-1 were pre- and postmenopausal, whereas women in STAR (P-2) were all postmenopausal at entry. Using Cox proportional hazards regression, we found slight but nonsignificant increased risks of invasive breast cancer among overweight and obese postmenopausal participants in STAR and P-1. Among premenopausal participants, an increased risk of invasive breast cancer was significantly associated with higher BMI (P = 0.01). Compared with BMI less than 25, adjusted HRs for premenopausal women were 1.59 for BMI 25 to 29.9 and 1.70 for BMI 30 or more. Our investigation among annually screened, high-risk participants in randomized, breast cancer chemoprevention trials showed that higher levels of BMI were significantly associated with increased breast cancer risk in premenopausal women older than 35 years, but not postmenopausal women.
Germline variation in DNA damage response may explain variable treatment outcomes in squamous cell carcinoma of the head and neck (SCCHN). By grouping patients according to stage and radiation ...treatment, we compared SCCHN survival with regard to ERCC2 A35931C (Lys751Gln, rs13181) and CCND1 G870A (Pro241Pro, rs9344) genotypes.
In a hospital-based SCCHN case series (all white, 24.7% female, mean age 58.4 years), this treatment-outcome cohort study genotyped 275 stage III-IV cases that were initially treated with radiation (with or without chemotherapy) and 80 stage III-IV and 130 stage I-II cases that were initially treated without radiation or chemotherapy and used Kaplan-Meier and Cox regression analyses to compare genotype groups on the basis of overall, disease-specific, progression-free, and recurrence-free survival rates.
ERCC2 35931 AA predicted worse survival in stage III-IV cases treated with radiation multiply-adjusted HR = 1.66, 95% confidence interval (CI), 1.15-2.40; HR over the first 3 follow-up years = 1.92; 95% CI, 1.28-2.88 and better survival in stage III-IV cases not treated with radiation (HR = 0.26; 95% CI, 0.11-0.62). Although not associated with survival in stage III-IV cancers treated with radiation (HR = 1.00; 95% CI, 0.67-1.51), CCND1-870 GG predicted better survival in stage III-IV cancers not treated with radiation (HR = 0.14; 95% CI, 0.04-0.50). Survival in stage I-II did not depend on ERCC2 A35931C or CCND1 G870A genotype.
Although promoting tumor progression in untreated patients, germline differences in DNA-repair or cell-cycle control may improve treatment outcome in patients treated with DNA-damaging agents.
ERCC2 A35931C may help distinguish advanced stage SCCHN with better outcomes from radiation treatment.
Genome-wide association studies (GWAS) have consistently identified specific lung cancer susceptibility regions. We evaluated the lung cancer–predictive performance of single-nucleotide polymorphisms ...(SNPs) in these regions.
Lung cancer cases (N = 778) and controls (N = 1166) were genotyped for 77 SNPs located in GWAS-identified lung cancer susceptibility regions. Variable selection and model development used stepwise logistic regression and decision-tree analyses. In a subset nested in the Pittsburgh Lung Screening Study, change in area under the receiver operator characteristic curve and net reclassification improvement were used to compare predictions made by risk factor models with and without genetic variables.
Variable selection and model development kept two SNPs in each of three GWAS regions, rs2736100 and rs7727912 in 5p15.33, rs805297 and rs1802127 in 6p21.33, and rs8034191 and rs12440014 in 15q25.1. The ratio of cases to controls was three times higher among subjects with a high-risk genotype in every one as opposed to none of the three GWAS regions (odds ratio, 3.14; 95% confidence interval, 2.02–4.88; adjusted for sex, age, and pack-years). Adding a three-level classified count of GWAS regions with high-risk genotypes to an age and smoking risk factor-only model improved lung cancer prediction by a small amount: area under the receiver operator characteristic curve, 0.725 versus 0.717 (p = 0.056); overall net reclassification improvement was 0.052 across low-, intermediate-, and high- 6-year lung cancer risk categories (<3.0%, 3.0%–4.9%, ≥5.0%).
Specifying genotypes for SNPs in three GWAS-identified susceptibility regions improved lung cancer prediction, but probably by an extent too small to affect disease control practice.
There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and ...HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal–Wallis tests were used to compare staining scores (intensity × percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (ρ) in all cases, and stratified by HPV status. HPV-negative HNSCC over-expressed EGFR median (range): 30 (0–300) relative to HPV-positive HNSCC 7.5 (0–200) (
P
= 0.006). VEGF and NOTCH1 were unrelated to HPV status (
P
> 0.05). EGFR was associated with VEGF in HPV-negative (ρ = 0.40,
P
= 0.01) but not HPV-positive HNSCC (ρ = 0.25,
P
= 0.20). NOTCH1 and VEGF were associated in HPV-negative (ρ = 0.40,
P
= 0.01) but not HPV-positive tumors (ρ = −0.12,
P
= 0.57). NOTCH1 was not associated with EGFR (
P
> 0.05). Our results are suggestive of heterogeneity in HNSCC angiogenesis. Future studies should explore angiogenesis mechanisms in HPV-positive and HPV-negative HNSCC.
Background In the practice of percutaneous coronary intervention, post-dilation often is performed after stent deployment to improve stent expansion. However, aggressive mechanical expansion is a ...risk factor of distal embolization and microvascular injury, especially for patients with acute myocardial infarction (AMI). Few studies have investigated the effects of post-dilation on medium-term clinical outcomes. Methods and Results Patients enrolled in the multicenter NHLBI Dynamic Registry between 2001 and 2006 were evaluated. Patients who were treated with ≥1 stent were studied. Patients with cardiogenic shock or history of coronary artery bypass graft surgery were excluded. Patients were followed up to 1 year. Because of the significant statistical interaction ( P = .02) between post-dilation and AMI status on the hazard of death/myocardial infarction (MI), post-dilation effects were estimated separately for patients who did and did not present with an AMI. Among the 1,358 patients who presented with an AMI, post-dilation was associated with a significantly higher risk of death/MI (hazard ratio HR = 1.78, 95% CI 1.12-2.83, P = .01), not associated with the risk of repeat revascularization (HR = 1.15, 95% CI 0.81-1.62, P = .43). Among the 3,001 patients who did not present with AMI, post-dilation was not associated with risks of death/MI (HR = 1.08, 95% CI 0.77-1.50, P = .67) or repeat revascularization (HR = 1.17, 95% CI 0.93-1.47, P = .19). Similar effects were observed for the restricted analysis with additional adjustment for lesion characteristics among the 1,039 AMI patients and 2,179 non-AMI patients with a single lesion treated. Conclusions Stent post-dilation is associated with an increased risk of death/MI in AMI patients but not in non-AMI patients. Further investigation is warranted.
Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apoptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via ...hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer.
Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements.
Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio OR = 1.7; 95% CI: 1.0-2.9, Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 95% CI: 1.1-3.3, Ptrend = .01), and insulin (OR = 2.1 95% CI: 1.2-3.6, Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 95% CI: 1.3-6.2, Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, 95% CI: 1.0-5.2, Ptrend = .04), and insulin (OR = 2.3 95% CI: 1.1-4.9, Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk.
Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.
It is generally accepted that delay in receiving treatment for breast cancer results in adverse outcomes. The purpose of this study was to evaluate the impact of delay in treatment after the ...diagnosis of metastatic disease on survival measured from metastatic breast cancer diagnosis and from first treatment while controlling for immortal time effect among patients with metastatic breast cancer. A total of 553 patients with breast cancer metastasis diagnosis from one large urban practice have been followed between January 1, 1999 and June 30, 2008. Prognostic factors and outcomes of these patients were analyzed using log-rank test and Cox regression model. Backward stepwise selection of covariates was conducted to assess the association of treatment delay with survival. The median survival was 40 months (range 1–114 months), with 265 (47.9%) women alive and 288 (52.1%) having died at the end of the follow-up period. Treatment delays of more than 12 weeks had impact on poor survival from first treatment than the delays of 4–12 weeks with borderline significance level (HR 1.76, 95% CI 0.99–3.13,
P
= 0.056) in multivariate analysis, adjusted by BMI, history of hypertension, ER/PR status, HER2 status, number of metastatic sites, and liver metastasis. Moreover, the interval of 12–24 weeks, compared to the interval of 4–12 weeks was associated with greater risk of death from first treatment (HR 2.39, 95% CI 1.19–4.77,
P
= 0.014). The treatment delay interval of >12 weeks was not related with survival since metastatic breast cancer diagnosis, compared to the 4–12 weeks of treatment delays. This study demonstrated that delays of over 12 weeks in receiving treatment for metastatic breast cancer were related to adverse survival outcomes measured from initiation of first treatment. The findings of this study support targeted efforts to ensure prompt treatment initiation in patients diagnosed with metastatic breast cancer.
Highlights • EGFR polymorphisms were associated with HNSCC risk in a large case–control population. • One EGFR variant was associated with tobacco-related risk. • Three EGFR variants were associated ...with tobacco-independent risk. • Tobacco-independent SNPs were intronic and resided near putative enhancer elements. • Our study underscores the importance of risk factor subset analyses.