Background: Observational studies have suggested that antioxidant nutrients may reduce cancer and overall mortality risks. However, most randomized trials have failed to show survival benefits. Examining nonlinear associations between antioxidant levels and health outcomes may help to explain these discrepant findings.
Methods: We evaluated all-cause, cancer, and cardiovascular mortality risks associated with quintiles (Q1–Q5) of serum antioxidant (vitamins C and E, β-carotene, and selenium) and vitamin A levels, in 16,008 adult participants of The Third National Health and Nutrition Examination Survey (NHANES III; 1988–1994).
Results: Over a median follow-up period of 14.2 years, there were 4,225 deaths, including 891 from cancer and 1,891 from cardiovascular disease. We observed a dose–response decrease in cancer and overall mortality risks with higher vitamin C levels. In contrast, for vitamin A, risk of cancer death decreased from Q1–Q2, with no further decline in risk at higher levels. For vitamin E, having levels in Q4 was associated with the lowest cancer mortality risk. Both vitamin A and E had U-shaped associations with all-cause mortality. Cancer mortality risks decreased from Q1–Q2 for β-carotene and from Q1–Q4 for selenium. However, for β-carotene and selenium, overall mortality risks decreased from Q1–Q2 but then did not change significantly with higher levels.
Conclusions: Antioxidant supplement use should be studied in the context of overall mortality and other competing mortality risks.
Background: Random periareolar fine-needle aspiration (RP-FNA) is increasingly used in trials of breast cancer prevention for biomarker assessments. DNA methylation markers may have value as surrogate endpoint biomarkers, but this requires identification of biologically relevant markers suitable for paucicellular, lymphocyte-contaminated clinical samples.
Methods: Unbiased whole-genome 5-aza-2'-deoxycytidine (5AZA)–induced gene expression assays, followed by several phases of qualitative and quantitative methylation-specific PCR (MSP) testing, were used to identify novel breast cancer DNA methylation markers optimized for clinical FNA samples.
Results: The initial 5AZA experiment identified 453 genes whose expression was potentially regulated by promoter region methylation. Informatics filters excluded 273 genes unlikely to yield useful DNA methylation markers. MSP assays were designed for 271 of the remaining genes and, ultimately, 33 genes were identified that were differentially methylated in clinical breast cancer samples, as compared with benign RP-FNA samples, and never methylated in lymphocytes. A subset of these markers was validated by quantitative multiplex MSP in extended clinical sample sets. Using a novel permutation method for analysis of quantitative methylation data, PSAT1, GNE, CPNE8, and CXCL14 were found to correlate strongly with specific clinical and pathologic features of breast cancer. In general, our approach identified markers methylated in a smaller subpopulation of tumor cells than those identified in published methylation array studies.
Conclusions: Clinically relevant DNA methylation markers were identified using a 5AZA-induced gene expression approach.
Background: Cutaneous melanomas have been hypothesized to arise through different pathways according to phenotype, body site, and sun exposure. To further test this hypothesis, we explored associations between phenotype and melanoma at different sites using a case–case comparative approach.
Methods: Melanoma patients (n = 762) aged 18 to 79 years and diagnosed from 2007 to 2010 were ascertained from pathology laboratories in Brisbane, Australia. Patients reported phenotypic information and a dermatologist counted melanocytic nevi and solar keratoses. We compared data for patients with trunk melanoma (n = 541, the reference group), head/neck melanoma (n = 122), or lentigo maligna melanoma (LMM) of the head/neck (n = 69). ORs and 95% confidence intervals were calculated using classical or polytomous logistic regression models.
Results: Compared with trunk melanoma patients, those with head/neck melanoma were significantly less likely to have high nevus counts (≥135: OR = 0.27; Ptrend = 0.0004). Associations between category of nevus count and LMM head/neck were weaker and significantly different (≥135: OR = 1.09; Ptrend = 0.69; Phomogeneity = 0.02). Patients with head/neck melanoma were more likely than those with truncal melanoma to have high solar keratosis counts (≥7: OR = 1.78, Ptrend = 0.04). Again, associations with LMM head/neck were weaker, albeit not significantly different (≥7: OR = 1.61; Ptrend = 0.42; Phomogeneity = 0.86).
Conclusion: Trunk melanomas are more strongly associated with nevus counts than head/neck melanomas, but are less strongly associated with number of solar keratoses, a marker of chronic sun exposure.
Background: Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We assessed these relationships in a cohort of the Copenhagen School Health Records Register (CSHRR).
Methods: The CSHRR comprises 372,636 school children. For boys born between the 1930s and 1969, birth weight and annual childhood heights—measured between ages 7 and 13 years—were analyzed in relation to prostate cancer risk. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI).
Results: There were 125,211 males for analysis, 2,987 of who were subsequently diagnosed with prostate cancer during 2.57 million person-years of follow-up. Height z-score was significantly associated with prostate cancer risk at all ages (HRs, 1.13 to 1.14). Height at age 13 years was more important than height change (P = 0.024) and height at age 7 years (P = 0.024), when estimates from mutually adjusted models were compared. Adjustment of birth weight did not alter the estimates. Birth weight was not associated with prostate cancer risk.
Conclusions: The association between childhood height and prostate cancer risk was driven by height at age 13 years.
Background: Effective screening and prevention strategies for bladder cancer require accurate risk stratification models. We developed models to predict the risk of bladder cancer based on clinical and sociodemographic data on participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial.
Methods: Baseline clinical and sociodemographic data were obtained from 149,542 PLCO participants, ages 55 to 74 years, without a prior history of bladder cancer. Cox proportional hazards models were used to predict the risk of all bladder cancers (ABC) and of high-grade bladder cancers (HGBC) from baseline information. We used the HGBC risk model to design a hypothetical bladder cancer mortality prevention trial.
Results: Over a median follow-up of 12 years, 1,124 men and 259 women developed bladder cancer (including 392 and 72 with HGBC, respectively). The incidence in men and in women was 133.6 and 29.6 cases per 100,000 person-years, respectively. Nomograms constructed for predicting the risk of ABC and HGBC had c-indices of 0.746 and 0.759, respectively. Age, race, education, smoking (intensity and duration), comorbidity, prostatitis, syphilis, and hormone replacement therapy use were statistically significant predictors in the models. We show that our risk model can be used to design a bladder cancer mortality prevention trial half the size of a trial designed without risk stratification.
Conclusion: Models to predict the risk of ABC and HGBC have been developed and validated.
Background: Excess body weight is an independent risk factor for primary liver cancer, and the role of adiponectin in the pathogenesis of obesity-related malignancies is a focus of research interest. Few prospective studies have examined the association between circulating adiponectin and liver cancer risk, so we investigated this association in a nested case–control study of a population-based prospective cohort in Japan.
Methods: From 18,628 target participants of ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or C virus infection at baseline (n = 1,544). Among these, 90 were newly diagnosed with primary liver cancer from 1993 through 2006, and matched to 177 controls. The ORs of liver cancer development based on plasma levels of adiponectin were estimated with a conditional logistic regression model.
Results: Median values of total and high-molecular-weight (HMW) adiponectin tended to be higher in the patients with liver cancer, and plasma levels of adiponectin were positively associated with liver cancer risk. Body mass index– and diabetes-adjusted ORs for the highest tertile of total and HMW adiponectin levels versus the lowest were 3.30 [95% confidence interval (CI), 1.45–7.53; Ptrend < 0.01] and 3.41 (95% CI, 1.50–7.73; Ptrend < 0.01), respectively. There was no effect modification by body mass index and diabetes.
Conclusions: Higher plasma adiponectin levels were associated with an increased risk of primary liver cancer in middle-aged Japanese adults with hepatitis virus infection.
Background: Antidiabetic medications (ADM) may modify colorectal cancer risk in patients with diabetes mellitus. We performed a systematic review and meta-analysis, evaluating the effect of metformin, thiazolidinediones (TZD), sulfonylureas, and insulin on colorectal cancer risk in diabetic patients.
Methods: We conducted a systematic search of multiple bibliographic databases, up to September 2012, for articles that evaluated exposure to metformin, TZD, sulfonylureas, and insulin, reported colorectal cancer risk in patients with diabetes mellitus, and reported OR or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CI) were estimated using the random-effects model.
Results: Fifteen studies reporting 13,871 cases of colorectal cancer in 840,787 patients with diabetes mellitus were included. Meta-analysis of observational studies showed an 11% reduction in colorectal cancer risk associated with metformin use (n = 9 studies; OR, 0.89; 95% CI, 0.81–0.99), whereas TZD use was not associated with colorectal cancer risk (n = 5 studies; OR, 0.96; 95% CI, 0.87–1.05). Conversely, a trend toward higher colorectal cancer risk was observed with sulfonylurea (n = 7 studies; OR, 1.11; 95% CI, 0.97–1.26) and insulin (n = 9 studies; OR, 1.33; 95% CI, 0.91–1.94) use, although these associations were not statistically significant. There was considerable heterogeneity across studies, partly explained by study location and adjustment for concomitant use of other ADMs. Post-hoc analysis of randomized controlled trials did not reveal any significant association between ADM and colorectal cancer risk.
Conclusions: Meta-analysis of published studies supports a protective association between metformin use and colorectal cancer risk in patients with diabetes mellitus.
Background: To establish, if among unaffected noncarrier relatives in a family with an established BRCA1/2 mutation, there is an increased risk of breast cancer.
Methods: We identified 49 women with breast cancer who were first-degree relatives of a pathogenic mutation carrier among 807 BRCA1/2 families but who tested negative for the specific mutation. A prospective analysis of breast cancer from date of family ascertainment was performed for first-degree relatives of proven BRCA1/2 mutation carriers and compared with population-expected incidence rates.
Results: Women who prospectively test negative for BRCA1/2 mutations showed excess risk of breast cancer to be confined to BRCA2 noncarriers with an observed:expected (O/E) ratio of 4.57 [95% confidence interval (CI) 2.50–7.67; P < 0.0001; O/E in BRCA1 noncarriers, 1.77]; this dropped to 2.01 for BRCA2 [relative risk (RR), 1.99; 95% CI, 0.54–5.10] from date of predictive test. Genotyping of 18 breast cancer susceptibility single-nucleotide polymorphisms (SNP) defined an RR of 1.31 for BRCA2 breast cancer phenocopies with a breast cancer diagnosis at age less than 60 years.
Conclusion: Noncarriers remain at risk in the prospective follow-up of women who tested negative for BRCA1/2. Women testing negative in BRCA2 families may have increased risk of breast cancer compared with population levels, particularly with strong breast cancer history in close relatives. Any increased risk in BRCA1 families is likely to be insufficient to recommend additional interventions.
Background: Nipple aspiration fluid (NAF) use as a biosample is limited by the variable yield across studies. We investigated the endocrine determinants of yield in an ongoing breast cancer case–control study.
Methods: One-hundred and eighteen women yielding ≥2 μL NAF and 120 non-yielders were included; serum hormones were measured; differences in median hormones were assessed using the Wilcoxon rank-sum test. ORs and 95% confidence intervals (95% CI) for yielder status relative to hormone levels were estimated using logistic regression, adjusting for parity and lactation, and, in premenopausal women, menstrual cycle phase (MCP).
Results: Prolactin concentrations were higher in yielders than non-yielders (premenopausal: 7.6 and 2.5 ng/mL, P < 0.01; postmenopausal 5.3 and 2.2 ng/mL; P < 0.01). Among premenopausal-yielders, estradiol was lower (64.3 vs. 90.5 pg/mL, MCP-adjusted P = 0.02). In separate menopausal status and parity-adjusted models, significant case–control differences persisted in prolactin: case OR 1.93 (95% CI, 1.35–2.77), control OR 1.64 (95% CI, 1.17–2.29). Premenopausal control yielders had higher progesterone (OR, 1.70; 95% CI, 1.18–2.46) and sex-hormone binding-globulin (OR, 2.09; 95% CI, 1.08–4.05) than non-yielders. Among parous women, further adjustment for lactation suggested a stronger positive association of serum prolactin with yield in cases than controls.
Conclusion: NAF-yielders show higher prolactin than non-yielders, regardless of menopause and parity; implications of this and other endocrine differences on NAF biomarkers of breast cancer risk deserve further study.
Background: Cigarette smoking is associated with the etiology of nasopharyngeal carcinoma; however, the influence of smoking on survival in patients with established nasopharyngeal carcinoma remains unknown.
Methods: We retrospectively analyzed 1,849 patients with nasopharyngeal carcinoma who were categorized as never, former, and current smokers. Cumulative effect of smoking was defined in terms of pack-years. Associations between cigarette exposure and survival were estimated by Cox proportional hazards model.
Results: The risks of death, progression, locoregional relapse, and distant metastasis were significantly higher for former and current smokers (all P ≤ 0.002) than never smokers. Heavy smokers with high pack-years had HRs for death of 3.31 [95% confidence interval (CI), 2.58–4.26; P < 0.001], for progression of 2.53 (95% CI, 2.03–3.16; P < 0.001), and for distant metastasis of 2.65 (95% CI, 1.89–3.70; P < 0.001). Specifically, in the cohort of 495 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, we obtained similarly significant results. All of the survival outcomes remained significant in multivariate analyses.
Conclusions: Pretreatment cigarette smoking is an independent, poor prognostic factor for patients with nasopharyngeal carcinoma, which is associated with increased risk of death, progression, locoregional relapse, and distant metastasis, with the risk increasing with pack-years.
Background: Few studies have examined the psychometric properties and invariance of scales measuring constructs relevant to colorectal cancer screening (CRCS). We sought to: (i) evaluate the factorial validity of four core constructs associated with CRCS (benefits, barriers, self-efficacy, and optimism); and (ii) examine measurement invariance by screening status (currently screened, overdue, never screened).
Methods: We used baseline survey data from a longitudinal behavioral intervention trial to increase CRCS among U.S. veterans. Respondents were classified as currently screened (n = 3,498), overdue (n = 418), and never screened (n = 1,277). The measurement model was developed using a random half of the sample and then validated with the second half of the sample and the full baseline sample (n = 5,193). Single- and multi-group confirmatory factor analysis was used to examine measurement invariance by screening status.
Results: The four-factor measurement model demonstrated good fit. Factor loadings, item intercepts, and residual item variance and covariance were invariant when comparing participants never screened and overdue for CRCS, indicating strict measurement invariance. All factor loadings were invariant among the currently screened and overdue groups. Only the benefits scale was invariant across current screeners and never screeners. Non-invariant items were primarily from the barriers scale.
Conclusion: Our findings provide additional support for the construct validity of scales of CRCS benefits, barriers, self-efficacy, and optimism. A greater understanding of the differences between current and never screeners may improve measurement invariance.
Background: Previous studies reported a positive association of body mass index (BMI) with microsatellite-stable (MSS) but not with microsatellite-instable (MSI-high) colorectal cancer. However, information from population-based studies conducted in representative age groups is so far limited.
Methods: We conducted a population-based case–control study (DACHS) in Southern Germany, including 1,215 patients with incident colorectal cancer and 1,891 matched controls with no upper age limit. Information on risk factors of colorectal cancer was obtained in standardized interviews. Microsatellite instability was analyzed using a mononucleotide marker panel.
Results: Median age among cases was 69 years, and 115 cases were classified MSI-high (9.5%). In multivariate analyses, BMI was positively associated with both risk of MSI-high colorectal cancer [per 5 kg/m2: OR, 1.71; 95% confidence interval (CI), 1.35–2.17] and risk of MSS colorectal cancer (OR, 1.20; 95% CI, 1.07–1.33). The association with MSI-high colorectal cancer was limited to women (OR, 2.04; 95% CI, 1.50–2.77; P interaction = 0.02) and most pronounced among ever users of postmenopausal hormone replacement therapy (OR, 4.68; 95% CI, 2.36–9.30; P interaction = 0.01). In case-only analyses, BMI was more strongly associated with MSI-high colorectal cancer than with MSS colorectal cancer among women (OR, 1.84; 95% CI, 1.13–1.82; P interaction = 0.01).
Conclusions: This population-based study confirms previous findings of increased risk of MSS colorectal cancer with obesity between both sexes and suggests that overweight and obesity may also be associated with increased risk of MSI-high colorectal cancer among women.
Background: Oxidative stress and resulting cellular damage have been suggested to play a role in the etiology of several chronic diseases, including cancer and cardiovascular disease. Identifying factors associated with reduced oxidative stress and resulting damage may guide future disease-prevention strategies.
Methods: In the VITamins And Lifestyle (VITAL) biomarker study of 209 persons living in the Seattle area, we examined the association between current use of several specialty supplements and oxidative stress, DNA damage, and DNA repair capacity. Use of glucosamine, chondroitin, fish oil, methylsulfonylmethane (MSM), coenzyme Q10 (CoQ10), ginseng, ginkgo, and saw palmetto was ascertained by a supplement inventory/interview, whereas the use of fiber supplements was ascertained by questionnaire. Supplements used by more than 30 persons (glucosamine and chondroitin) were evaluated as the trend across number of pills/week (non-use, <14 pills/week, 14+ pills/week), whereas less commonly used supplements were evaluated as use/non-use. Oxidative stress was measured by urinary 8-isoprostane and PGF2α concentrations using enzyme immunoassays (EIA), whereas lymphocyte DNA damage and DNA repair capacity were measured using the Comet assay. Multivariate-adjusted linear regression was used to model the associations between supplement use and oxidative stress/DNA damage.
Results: Use of glucosamine (Ptrend: 0.01), chondroitin (Ptrend: 0.003), and fiber supplements (P: 0.01) was associated with reduced PGF2α concentrations, whereas CoQ10 supplementation was associated with reduced baseline DNA damage (P: 0.003).
Conclusions: Use of certain specialty supplements may be associated with reduced oxidative stress and DNA damage.
Background: Several reports indicate that inherited mutations in the PALB2 gene predispose to breast cancer. However, there is little agreement about the clinical relevance and usefulness of mutation screening in this gene. We analyzed the prevalence and spectrum of germline mutations in PALB2 to estimate their contribution to hereditary breast and/or ovarian cancer in the Czech Republic.
Methods: The entire PALB2 coding region was sequenced in 409 breast/ovarian cancer patients negative for BRCA1 and BRCA2 mutations. Testing for large genomic rearrangements (LGR) was performed by multiplex ligation-dependent probe amplification (MLPA) analysis.
Results: We have identified 13 different pathogenic alterations including 10 truncating mutations and three LGRs in 16 of 409 patients (3.9%), whereas one truncating mutation was found in a group of 1,226 controls (0.08%; P = 2.6 x 10–9). Three novel LGRs included deletions involving exons 7–8 and 9–10, respectively, and a duplication spanning exons 9–11. Five frameshift and two nonsense mutations were novel, whereas three truncating mutations were described previously. The only recurrent mutation was the c.172_175delTTGT detected in four unrelated breast cancer individuals.
Conclusions: Our analyses demonstrated the significant role of the PALB2 gene in breast cancer susceptibility. The highest frequency of PALB2 mutations (comparable with that previously reported for BRCA2) was found in a subgroup of patients with hereditary breast cancer (HBC) (13/235; 5.5%).
Background: The associations of ERG overexpression with clinical behavior and molecular pathways of prostate cancer are incompletely known. We assessed the association of ERG expression with AR, PTEN, SPINK1, Ki-67, and EZH2 expression levels, deletion, and mutations of chromosomal region 3p14 and TP53, and clinicopathologic variables.
Methods: The material consisted of 326 prostatectomies, 166 needle biopsies from men treated primarily with endocrine therapy, 177 transurethral resections of castration-resistant prostate cancers (CRPC), and 114 CRPC metastases obtained from 32 men. Immunohistochemistry, FISH, and sequencing was used for the measurements.
Results: ERG expression was found in about 45% of all patient cohorts. In a multivariate analysis, ERG expression showed independent value of favorable prognosis (P = 0.019). ERG positivity was significantly associated with loss of PTEN expression in prostatectomy (P = 0.0348), and locally recurrent CRPCs (P = 0.0042). Loss of PTEN expression was associated (P = 0.0085) with shorter progression-free survival in ERG-positive, but not in negative cases. When metastases in each subject were compared, consistent ERG, PTEN, and AR expression as well as TP53 mutations were found in a majority of subjects.
Conclusions: A similar frequency of ERG positivity from early to late stage of the disease suggests lack of selection of ERG expression during disease progression. The prognostic significance of PTEN loss solely in ERG-positive cases indicates interaction of these pathways. The finding of consistent genetic alterations in different metastases suggests that the major genetic alterations take place in the primary tumor.
Background: Observational studies have reported conflicting results between parity and kidney cancer risk. To our knowledge, a comprehensive and quantitative assessment of the association between parity and kidney cancer has not been reported. Thus, we conducted a systematic review and dose–response meta-analysis of published epidemiologic studies to summarize the evidence of this association.
Methods: Relevant published studies of parity and kidney cancer were identified using MEDLINE (PubMed) database through end of June 2013. Two authors independently assessed eligibility and extracted data. Six prospective and eight case–control studies reported relative risk (RR) estimates and 95% confidence intervals (CI) of kidney cancer associated with parity or parity number. Fixed- or random-effects models were used to estimate summary relative risk.
Results: The summary relative risk of kidney cancer for the parity versus nulliparous was 1.23 (95% CI, 1.10–1.36; Q = 12.41; P = 0.413; I2 = 3.3%). In addition, significant association was also found for the highest versus lowest parity number, with summary RR = 1.36 (95% CI, 1.19–1.56; Q = 8.24; P = 0.766; I2 = 0%). In the dose–response analysis, the summary per one live birth relative risk was 1.08 (95% CI: 1.05–1.10; Q = 9.34; P = 0.500; I2 = 0%), also indicating the positive effect of parity on kidney cancer risk. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses.
Conclusions: In summary, findings from this meta-analysis suggest that ever parity and higher parity number is significantly associated with increased risk of kidney cancer.
Background: Overexpression of prostate-specific membrane antigen (PSMA) in tumor tissue and serum has been linked to increased risk of biochemical recurrence in surgically treated prostate cancer patients, but none of the studies have assessed its association with disease-specific mortality.
Methods: We examined whether high PSMA protein expression in prostate tumor tissue was associated with lethal disease, and with tumor biomarkers of progression, among participants of two U.S.-based cohorts (n = 902, diagnosed 1983–2004). We used Cox proportional hazards regression to calculate multivariable HRs and 95% confidence intervals (CI) of lethal prostate cancer, defined as disease-specific death or development of distant metastases (n = 95). Partial Spearman rank correlation coefficients were used to correlate PSMA with tumor biomarkers.
Results: During an average 13 years of follow-up, higher PSMA expression at prostatectomy was significantly associated with lethal prostate cancer (age-adjusted HRQuartile(Q)4vs.Q1 = 2.42; Ptrend < 0.01). This association was attenuated and nonsignificant (multivariable-adjusted HRQ4vs.Q1 = 1.01; Ptrend = 0.52) after further adjusting for Gleason score and prostate-specific antigen (PSA) at diagnosis. High PSMA expression was significantly (P < 0.05) correlated with higher Gleason score and PSA at diagnosis, increased tumor angiogenesis, lower vitamin D receptor and androgen receptor expression, and absence of ets-related gene (ERG) expression.
Conclusions: High tumor PSMA expression was not an independent predictor of lethal prostate cancer in the current study. PSMA expression likely captures, in part, malignant features of Gleason grade and tumor angiogenesis.
Background: MicroRNAs (miRNA) are abundant in the circulation and play a central role in diverse biologic processes; they may be useful for early diagnosis of hepatocellular carcinoma.
Methods: We conducted a two-phase, case–control study (20 pairs for the discovery set and 49 pairs for the validation set) to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiates hepatocellular carcinoma cases from controls. Taqman low-density arrays were used to examine genome-wide miRNA expression for the discovery set, and quantitative real-time PCR was used to validate candidate miRNAs for both discovery and validation sets.
Results: Sixty-six miRNAs were found to be significantly overexpressed in plasma of hepatocellular carcinoma cases compared with controls after adjusting for false discovery rate (P < 0.05). A volcano plot indicated that seven miRNAs had greater than 2-fold case–control differences with P < 0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p, and miR-520b) detectable in all samples with varied expression levels were further validated in a validation set. MiR-483-5p was statistically significantly overexpressed in hepatocellular carcinoma cases compared with controls (3.20 vs. 0.82, P < 0.0001). Hepatocellular carcinoma risk factors and clinic-pathological characteristics did not influence miR-483-5p expression. The combination of plasma miR-483-5p level and hepatitis C virus status can significantly differentiate hepatocellular carcinoma cases from controls with an area under the curve of 0.908 (P < 0.0001). The sensitivity and specificity were, respectively, 75.5% and 89.8%.
Conclusions: These preliminary results suggest the importance of dysregulated circulating miR-483-5p as a potential hepatocellular carcinoma biomarker.
Background: The respiratory quotient (RQ), defined as the ratio of carbon dioxide exhaled to oxygen uptake, reflects substrate utilization when energy is expended. Fat and alcohol have RQ values of approximately 0.7, compared with 1.0 for carbohydrate, and approximately 0.8 for protein. Here, the association between RQ and postmenopausal breast cancer risk is studied.
Methods: Paired RQ measurements were obtained, separated by approximately 6 months, for women in the reliability subset of a Women's Health Initiative (WHI) Nutrition and Physical Activity Assessment Study. Linear regression of the average of the paired log RQ assessments on a corresponding log food quotient (FQ) average and other study subject characteristics, including age, body mass index, race, and education, yielded calibration equations for predicting RQ.
Results: Calibration equations, using any of food frequency, food record, or dietary recall data, explained an appreciable fraction of measured log RQ variation, and these were used to compute calibrated RQ estimates throughout WHI cohorts. Calibrated RQ estimates using 4-day food record (4DFR) data related inversely (P = 0.004) to (invasive) breast cancer risk in the WHI Dietary Modification trial comparison group, and corresponding RQ estimates using food-frequency data related inversely (P = 0.002) to breast cancer incidence in this cohort combined with the larger WHI observational study.
Conclusion: Although preliminary, these analyses suggest a substantially higher postmenopausal breast cancer risk among women having relatively low RQ.
Background: Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear.
Methods: We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women's Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the Surveillance Epidemiology and End Results Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models.
Results: From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for body mass index (BMI) and other cofounders (Ptrend = 0.0005). Compared with nondrinkers of SSB, the risk was 78% higher [95% confidence intervals (CI), 1.32–2.40] among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk.
Conclusion: Higher intake of SSB and sugars was associated with an increased risk of type I, but not type II, endometrial cancer.
Background: Mammographic density, the area of the mammographic image that appears white or bright, predicts breast cancer risk. We estimated the proportions of variance explained by questionnaire-measured breast cancer risk factors and by unmeasured residual familial factors.
Methods: For 544 MZ and 339 DZ twin pairs and 1,558 non-twin sisters from 1,564 families, mammographic density was measured using the computer-assisted method Cumulus. We estimated associations using multilevel mixed-effects linear regression and studied familial aspects using a multivariate normal model.
Results: The proportions of variance explained by age, body mass index (BMI), and other risk factors, respectively, were 4%, 1%, and 4% for dense area; 7%, 14%, and 4% for percent dense area; and 7%, 40%, and 1% for nondense area. Associations with dense area and percent dense area were in opposite directions than for nondense area. After adjusting for measured factors, the correlations of dense area with percent dense area and nondense area were 0.84 and –0.46, respectively. The MZ, DZ, and sister pair correlations were 0.59, 0.28, and 0.29 for dense area; 0.57, 0.30, and 0.28 for percent dense area; and 0.56, 0.27, and 0.28 for nondense area (SE = 0.02, 0.04, and 0.03, respectively).
Conclusions: Under the classic twin model, 50% to 60% (SE = 5%) of the variance of mammographic density measures that predict breast cancer risk are due to undiscovered genetic factors, and the remainder to as yet unknown individual-specific, nongenetic factors.
Background: Cancer is the number one cause of death among men in China. Cigarette smoking is the most preventable cause of cancer. Data on the impact of continued smoking after cancer diagnosis on survival of patients with cancer are sparse.
Methods: We studied the association between postdiagnosis smoking and risk of all-cause death among 1,632 incident cancer patients in the Shanghai Cohort Study, a population-based prospective cohort of 18,244 men in Shanghai. The change of smoking status after baseline interview was ascertained through annual in-person interviews. Cox proportional hazards regression models were used to estimate HR and 95% confidence interval (CI) for all-cause mortality associated with change in smoking status.
Results: Patients who continued smoking after cancer diagnosis experienced a statistically significant 59% (95% CI, 36–86) increase in risk of death compared with patients with cancer who did not smoke after cancer diagnosis. Among current smokers at cancer diagnosis, HRs (95% CIs) were 1.79 (1.49–2.16) in all patients with cancer, 2.36 (1.63–3.42) in patients with lung cancer, 1.63 (0.98–2.73) in patients with stomach cancer, 2.31 (1.40–3.81) in patients with colorectal cancer, and 2.95 (1.09–7.95) in patients with bladder cancer who continued smoking compared with their counterparts who stopped smoking after cancer diagnosis.
Conclusion: Postdiagnosis cigarettes smoking significantly increased the risk of death for male patients with cancer.
Background: Increased risk of skin cancer by indoor tanning has drawn public attention. However, there are arguments that tanning bed use increases vitamin D production, which may therefore prevent internal cancers.
Methods: We followed 73,358 female nurses for 20 years (1989–2009) in the Nurses' Health Study II and investigated the frequency of tanning bed use during high school/college and at ages 25 to 35 in relation to the incidence of total cancers (excluding skin cancers). We used multivariate Cox proportional hazards models to estimate the HRs and 95% confidence intervals (CI) of total cancers and each individual major cancer with more than 100 cases.
Results: During follow-up, a total of 4,271 internal cancer–related cases were diagnosed. No association was found between tanning bed use and risk of total cancers (multivariable-adjusted HR, 0.99; 95% CI, 0.95–1.04 for every 4 times/y use on average during high school/college and at ages 25–35). In addition, no association was found for the risk of any individual major cancers, such as breast cancer, thyroid cancer, colorectal cancer, non-Hodgkin lymphoma, or endometrial cancer.
Conclusions: Our data do not suggest any association between the use of tanning beds and risk of internal cancers.