Shift work involving disruption of circadian rhythms has been classified as a probable cause of human cancer by the International Agency for Research on Cancer, based on limited epidemiologic evidence and abundant experimental evidence. The authors investigated this association in a population-based prospective cohort study of Chinese women. At baseline (1996–2000), information on lifetime occupational history was obtained from 73,049 women. Lifetime night-shift exposure indices were created using a job exposure matrix. During 2002–2004, self-reported data on frequency and duration of night-shift work were collected. Hazard ratios and 95% confidence intervals, adjusted for major breast cancer risk factors, were calculated. During follow-up through 2007, 717 incident cases of breast cancer were diagnosed. Breast cancer risk was not associated with ever working the night shift on the basis of the job exposure matrix (adjusted hazard ratio = 1.0, 95% confidence interval: 0.9, 1.2) or self-reported history of night-shift work (adjusted hazard ratio = 0.9, 95% confidence interval: 0.7, 1.1). Risk was also not associated with frequency, duration, or cumulative amount of night-shift work. There were no indications of effect modification. The lack of an association between night-shift work and breast cancer adds to the inconsistent epidemiologic evidence. It may be premature to consider shift work a cause of cancer.
breast neoplasms; China; prospective studies; work schedule tolerance
We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers.
renal cell cancer; incidence trends; cohort studies; smoking; obesity; hypertension; diet; occupation; genetic polymorphism; somatic mutation
Gastric cancer incidence rates are consistently lower in women than men in both high and low‐risk regions worldwide. Sex hormones, such as progesterone and estrogen, may protect women against gastric cancer.
To investigate the association of menstrual and reproductive factors and gastric cancer risk.
These associations were prospectively investigated in 73 442 Shanghai women. After 419 260 person‐years of follow‐up, 154 women were diagnosed with gastric cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, body mass index, education, income, and cigarette use.
No associations were observed between gastric cancer risk and age of menarche, number of children, breast feeding, or oral contraceptive use. In contrast, associations were observed with age of menopause (HR 0.80 per five‐year increase in menopausal age, 95% CI 0.66–0.97), years of fertility (participants with less than 30 years of fertility were at increased risk compared with those with 30–36 years of fertility, HR 1.90, 95% CI 1.25–2.90), years since menopause (HR 1.26 per five years, 95% CI 1.03–1.53), and intrauterine device use (HR for users 1.61, 95% CI 1.08–2.39).
These results support the hypothesis that female hormones play a protective role in gastric cancer risk.
stomach neoplasms; cohort studies; prospective studies; hormones
Telomeres are specialized chromatin structures essential for maintenance of chromosomal integrity and stability. Abnormal alteration of telomere length has been linked to several cancers; however, epidemiologic evidence regarding the association of telomere length with colorectal cancer risk has been conflicting.
We conducted a nested case-control study to evaluate the association between telomere length and colorectal cancer risk using peripheral blood samples collected prior to cancer diagnosis. The study included 441 women with incident colorectal cancer and 549 matched controls. Monochrome multiplex quantitative PCR was applied to measure relative telomere length. Multiple logistic regressions were used to derive adjusted odds ratios (OR) with 95% confidence intervals (CI) as the measure of association between telomere length and subsequent colorectal cancer risk.
A U-shaped association was observed between telomere length and colorectal cancer risk (test for nonlinearity P = 0.0112). Women with telomere length in the third quintile (40th to 60th percentiles) had the lowest risk of colorectal cancer, and the risks were elevated with a shorter or longer telomere length. This U-shaped association did not statistically differ for colon cancer and rectum cancer.
Conclusions and Impact
Our prospective study revealed a U-shaped association between telomere length in peripheral blood cells and colorectal cancer risk. Our findings provide strong evidence that both very short and very long telomeres are associated with increased risk of colorectal cancer.
Calcium intake has been promoted due to its proposed benefit on bone health, particularly among the older population. However, concerns have been raised about the potential adverse effect of high calcium intake on cardiovascular health.
Dietary and supplemental calcium intakes were assessed at baseline (1995–96) in 388,229 men and women aged 50–71 years in the National Institutes of Health (NIH)–AARP Diet and Health Study. Supplemental calcium intake included calcium from multivitamins and individual calcium supplements. Cardiovascular disease (CVD) deaths were ascertained using the National Death Index. Multivariate Cox Proportional hazard models adjusted for demographic, lifestyle and dietary variables were used to estimate relative risks (RRs) and 95% confidence intervals (CIs).
During an average of 12 years of follow-up, 7904 and 3874 CVD deaths in men and women, respectively, were identified. Supplements containing calcium were used by 51% of men and 70% of women. In men supplemental calcium intake was associated with an elevated risk of CVD death (RR>1000 vs. 0 mg/day =1.20, 95% CI: 1.05–1.36), more specifically with heart disease death (RR=1.19, 95% CI: 1.03–1.37), but not significantly with cerebrovascular disease death (RR=1.14, 95% CI: 0.81–1.61). In women, supplemental calcium intake was not associated with CVD death (RR= 1.06, 95% CI: 0.96, 1.18), heart disease death (RR=1.05, 95% CI: 0.93–1.18) or cerebrovascular disease death (RR=1.08, 95% CI: 0.87–1.33). Dietary calcium intake was not related to CVD death in either men or women.
Our finding suggests that high intake of supplemental calcium is associated with an excess risk of CVD death in men, but not in women. Additional studies are needed to investigate the effect of supplemental calcium use beyond bone health.
This study evaluated associations of various anthropometric measures of adiposity with a panel of inflammatory and oxidative stress markers in a relatively lean population of Chinese women.
This analysis included 1,005 Chinese women aged 40-70 years. Plasma concentrations of inflammatory and oxidative stress markers were measured. Anthropometric measurements were taken by trained interviewers.
Body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were all positively and linearly associated with the inflammatory markers, CRP, TNF-α, soluble TNF-receptor 1 (sTNF-R1), and IL-6. A significant positive association of these measures of adiposity with the oxidative stress marker F2-IsoP-M, a metabolite of F2-IsoPs, but with not F2-IsoPs was found. Differences in biomarkers between extreme quartiles of anthropometric measurements varied widely, ranging from 9.7% for sTNF-R1 to 162.0% for CRP. For each specific biomarker, various anthropometric measurements exhibited similar ability to explain variations in the biomarker, with the biggest partial r2 (11%) observed for CRP.
This study suggests that both general adiposity (measured by BMI) and central adiposity (measured by WC and WHtR) are positively and similarly associated with various markers of inflammation and oxidative stress in relatively lean Chinese women. The metabolite F2-IsoP-M of F2-IsoPs may be a better marker of in vivo oxidative stress than its parent compounds.
adiposity; inflammation; oxidative stress; biomarker
Soy and some of its constituents, such as isoflavones, have been shown to affect the inflammatory process in animal studies. The association between soy food intake and inflammatory markers has not been evaluated adequately in humans.
Our aim was to evaluate whether higher intake of soy foods was inversely associated with inflammatory markers in 1,005 middle-aged Chinese women.
In this cross-sectional study, dietary intake of soy foods was assessed by a validated food frequency questionnaire and by a 24-hour recall when biospecimens were procured. A general linear model was used to estimate the geometric means of selected inflammatory markers, including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNFα), soluble IL-6 receptor, soluble GP130, soluble TNF receptors 1 and 2, and C-reactive protein, across categories of soy food intake after adjusting for age, lifestyle and dietary factors, and history of infectious or inflammation-related diseases.
We found that multivariable-adjusted geometric mean concentrations of IL-6 and TNFα were inversely associated with quintiles of soy food intake, with a difference between the highest and lowest quintiles of 25.5% for IL-6 (P for trend = 0.008) and 14% for TNFα (P for trend = 0.04). Similar inverse associations were found for TNFα (P for trend = 0.003), soluble TNF receptor 1 (P for trend=0.01), soluble TNF receptor 2 (P for trend=0.02), IL-1β (P for trend=0.05), and IL-6 (P for trend=0.04) when soy food consumption was assessed by the frequency of consumption in the preceding 24 hours. No significant associations were found for other markers studied.
This study suggests that soy food consumption is related to lower circulating levels of IL-6, TNFα, and soluble TNF receptors 1 and 2 in Chinese women.
Soy; Inflammation; Interleukin-1β; Interleukin-6; Tumor necrosis factor-α
In vitro studies have found that flavanol epigallocatechin (EGC) and flavonols, but not flavanol epicatechin (EC), activate glutathione s-transferases (GST), a family of phase II enzymes that detoxify reactive oxygen species, such as catechol estrogen metabolites. This study was designed to investigate prospectively whether urinary excretion of tea polyphenols interacts with GST polymorphisms to influence breast cancer risk.
Subjects and Methods
We conducted a study of 352 incident breast cancer cases and 701 individually-matched controls nested within the Shanghai Women’s Health Study cohort of women aged 40–70 years at baseline. Liquid chromatography tandem mass spectrometry was used to measure urinary excretion of flavanols and flavonols. Real-time multiplex PCR was used to quantify the copy number variation in the GSTM1 and GSTT1 genes.
Urinary excretion of flavonols and flavanols, particularly EGC (p=0.02), was significantly higher among women null for GSTM1 than those positive for GSTM1. Flavonols and flavanols (EGC in particular) were associated with a reduced risk of breast cancer among those null for GSTM1 and GSTT1, with a p-value of 0.04 for the interaction between EGC and GSTM1 polymorphism. In contrast, among women possessing both GSTM1 and GSTT1, breast cancer risk increased with levels of flavonols, particularly kaempferol.
The differential associations between polyphenols and breast cancer risk by GST polymorphisms, if confirmed, may provide a new avenue for the personalized prevention of breast cancer.
tea polyphenols; flavonol; flavanol; genomic polymorphism; interaction
Incidence of kidney cancer has been increasing over the past three decades, with more rapid increases and higher incidence rates among blacks than whites in the United States. An association between cigarette smoking and renal cell carcinoma (RCC), the most common form of kidney cancer, has been reported for whites, but the association in blacks is less clear.
The association between smoking and RCC was examined in 1,217 incident cases and 1,235 population controls frequency-matched on age, race, gender and study site in the Kidney Cancer Study in Detroit, MI and Chicago, IL.
In white individuals, increasing duration and number of pack years of were both associated with increased risk of RCC after adjusting for age, gender, education, study site, body mass index (BMI) and history of hypertension (p-trend=0.0002 and p-trend=0.002, respectively). Among black individuals, RCC risk increased with duration of smoking (p- trend=0.02), but not other measures. Compared to current smokers, RCC risk decreased with increasing years of smoking cessation among both whites and blacks (p- trend=0.01 and 0.02, respectively). When examining risk according to hypertension history, associations between smoking and RCC risk were observed only among individuals who reported never having been diagnosed with hypertension. Similarly, cigarette smoking was associated with increased risk of RCC among non-obese individuals, but not among those with BMI≥30 kg/m2.
Our observation that smoking is associated with RCC only in non-obese individuals and those with no history of hypertension are novel findings
The complex relationships between RCC, smoking, hypertension and obesity require additional confirmation.
Renal Cell Carcinoma; Cigarette Smoking; Hypertension; Body Mass Index; Race/Ethnicity
Background & Aims
Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett’s esophagus (BE). We investigated whether tobacco smoking and other factors increase risk for BE.
We analyzed data from 5 case-control studies included in the international Barrett’s and Esophageal Adenocarcinoma Consortium. We compared data from subjects with BE (n=1059) with those from subjects with gastroesophageal reflux disease (GERD controls, n=1332) and population-based controls (n=1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for BE.
Subjects with BE were significantly more likely to have ever-smoked cigarettes than the population-based controls (odds ratio [OR]=1.67; 95% confidence interval [CI], 1.04–2.67) or GERD controls (OR=1.61; 95% CI, 1.33–1.96). Increasing pack-years of smoking increased the risk for BE. There was evidence for a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (0.25–0.52).
Cigarette smoking is a risk factor for BE. The association strengthened with increased exposure to smoking until ~ 20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to the development of BE.
BEACON; esophageal cancer; population study; tobacco
Background & Aims
Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) has been reported to reduce risks for esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations.
We performed a pooled analysis of 6 population-based studies within the Barrett's and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model.
Compared to non-users, individuals who have used NSAIDs had a statistically significant, reduced risk of EAC (OR=0.68; 95% CI, 0.56–0.82); they also appeared to have a reduced risk of EGJA (OR=0.84; 95% CI, 0.68–1.03). Similar reductions in risk were observed among individuals who took aspirin or non-aspirin NSAIDs. The highest levels of frequency (≥daily) and duration (≥10 years) of NSAID use were associated with an approximately 40% reduction in risk for EAC: OR=0.56 (95% CI, 0.43–0.73; P-trend, <.001) and OR=0.63 (95% CI, 0.45–0.90; P-trend, 0.04), respectively.
Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, pooled analysis indicates a role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction.
BEACON; Esophageal Neoplasm; Stomach Cancer; Anti-Inflammatory Agent
Magnesium (Mg) and calcium (Ca) antagonise each other in (re)absorption, inflammation and many other physiological activities. Based on mathematical estimation, the absorbed number of Ca or Mg depends on the dietary ratio of Ca to Mg intake. We hypothesise that the dietary Ca/Mg ratio modifies the effects of Ca and Mg on mortality due to gastrointestinal tract cancer and, perhaps, mortality due to diseases occurring in other organs or systems.
Population-based cohort studies (The Shanghai Women's Health Study and the Shanghai Men's Health Study) conducted in Shanghai, China.
74 942 Chinese women aged 40–70 years and 61 500 Chinese men aged 40–74 years participated in the study.
Primary outcome measures
All-cause mortality and disease-specific mortality.
In this Chinese population with a low Ca/Mg intake ratio (a median of 1.7 vs around 3.0 in US populations), intakes of Mg greater than US Recommended Daily Allowance (RDA) levels (320 mg/day among women and 420 mg/day among men) were related to increased risks of total mortality for both women and men. Consistent with our hypothesis, the Ca/Mg intake ratio significantly modified the associations of intakes of Ca and Mg with mortality risk, whereas no significant interactions between Ca and Mg in relation to outcome were found. The associations differed by gender. Among men with a Ca/Mg ratio >1.7, increased intakes of Ca and Mg were associated with reduced risks of total mortality, and mortality due to coronary heart diseases. In the same group, intake of Ca was associated with a reduced risk of mortality due to cancer. Among women with a Ca/Mg ratio ≤1.7, intake of Mg was associated with increased risks of total mortality, and mortality due to cardiovascular diseases and colorectal cancer.
These results, if confirmed, may help to understand the optimal balance between Ca and Mg in the aetiology and prevention of these common diseases and reduction in mortality.
EPIDEMIOLOGY; NUTRITION & DIETETICS
Background Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals.
Methods Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing.
Results Age [β = −0.011% of 5-methyl-cytosine (%5mC)/year, 95% confidence interval (CI) −0.020 to −0.001%5mC/year] and alcohol drinking (β = −0.214, 95% CI −0.415 to −0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = −0.385, 95% CI −0.665 to −0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = −0.038, 95% CI −0.065 to −0.012) association with LINE-1 methylation, respectively.
Conclusions Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes.
Blood; DNA methylation; epigenetics; meta-analysis; repetitive elements
Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r2 = 0.64, D ′ = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10−10 and P = 6.07 × 10−9, respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13–1.26] for rs718314 and 1.18 (95% CI: 1.12–1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist–hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.
Low circulating levels of Coenzyme Q10 (CoQ10) have been associated with increased cancer incidence and poor prognosis for a number of cancer types, while a recent prospective study observed a positive association for CoQ10 with breast cancer risk.
We prospectively examined the association of plasma CoQ10 with breast cancer risk in a nested case-control study of Chinese women within the Shanghai Women's Health Study (SWHS). Pre-diagnostic plasma samples were obtained from 340 cases and 653 age-matched controls and analyzed for total CoQ10.
A borderline significant inverse association for breast cancer incidence with plasma CoQ10 level was observed using a conditional logistic regression model adjusted for age and age at first live birth, which became significant after elimination of cases diagnosed within one year of blood draw (ptrend = 0.03). This association was independent of menopausal status. Plasma CoQ10 levels were also observed to be significantly associated with circulating γ-tocopherol (r = 0.50; p < 0.0001) and with α-tocopherol (r =0.38; p < 0.0001) levels.
Circulating levels of CoQ10 were generally low in this population and the observed association with breast cancer risk may be limited to those women with exceptionally low values.
This study reports an inverse relationship between circulating CoQ10 and breast cancer risk, while the only other prospective study of CoQ10 and breast cancer to date found a positive association. Lower levels of CoQ10 in the SWHS population suggests that the two studies may not be contradictory and indicates a possible non-linear (U-shaped) association of CoQ10 with risk.
Generic job-exposure matrices (JEMs) are often used in population-based epidemiologic studies to assess occupational risk factors when only the job and industry information of each subject is available. JEM ratings are often based on professional judgment, are usually ordinal or semi-quantitative, and often do not account for changes in exposure over time. We present an empirical Bayesian framework that combines ordinal subjective JEM ratings with benzene measurements. Our aim was to better discriminate between job, industry, and time differences in exposure levels compared to using a JEM alone.
We combined 63 221 short-term area air measurements of benzene exposure (1954–2000) collected during routine health and safety inspections in Shanghai, China, with independently developed JEM intensity ratings for each job and industry using a mixed-effects model. The fixed-effects terms included the JEM intensity ratings for job and industry (both ordinal, 0–3) and a time trend that we incorporated as a b-spline. The random-effects terms included job (n = 33) and industry nested within job (n = 399). We predicted the benzene concentration in two ways: (i) a calibrated JEM estimate was calculated using the fixed-effects model parameters for calendar year and JEM intensity ratings; (ii) a job-/industry-specific estimate was calculated using the fixed-effects model parameters and the best linear unbiased predictors from the random effects for job and industry using an empirical Bayes estimation procedure. Finally, we applied the predicted benzene exposures to a prospective population-based cohort of women in Shanghai, China (n = 74 942).
Exposure levels were 13 times higher in 1965 than in 2000 and declined at a rate that varied from 4 to 15% per year from 1965 to 1985, followed by a small peak in the mid-1990s. The job-/industry-specific estimates had greater differences between exposure levels than the calibrated JEM estimates (97.5th percentile/2.5th percentile exposure level, BGR95B: 20.4 versus 3.0, respectively). The calibrated JEM and job-/industry-specific estimates were moderately correlated in any given year (Pearson correlation, rp = 0.58). We classified only those jobs and industries with a job or industry JEM exposure probability rating of 3 (>50% of workers exposed) as exposed. As a result, 14.8% of the subjects and 8.7% of the employed person-years in the study population were classified as benzene exposed. The cumulative exposure metrics based on the calibrated JEM and job-/industry-specific estimates were highly correlated (rp = 0.88).
We provide a useful framework for combining quantitative exposure data with expert-based exposure ratings in population-based studies that maximized the information from both sources. Our framework calibrated the ratings to a concentration scale between ratings and across time and provided a mechanism to estimate exposure when a job/industry group reported by a subject was not represented in the exposure database. It also allowed the job/industry groups’ exposure levels to deviate from the pooled average for their respective JEM intensity ratings.
benzene; job-exposure matrix; mixed-effects models; retrospective exposure assessment
The control of the host cytokine network is known to influence gastric cancer susceptibility; the specific inflammatory responses in gastric carcinogenesis remain unclear.
We prospectively examined the relationships of plasma levels of interleukin (IL)-1β, IL6, IL8 and tumor necrosis factor (TNF)-α to gastric cancer risk within The Shanghai Women’s Health Study. Two controls were matched to each case by age, menopausal status and sample collection parameters. The associations of gastric cancer risk and tertile of cytokine levels were estimated by odds ratios (ORs) and 95 per cent confidence intervals (% CIs) from conditional logistic regression, adjusting for education.
During a median follow-up period of 4 years (range: 0.1–8), 141 women developed gastric cancer and were matched to 282 cancer-free study participants. Elevated levels of plasma IL6 were associated with an increased risk of gastric cancer (Ρtrend=0.04). Risk increased 70% (OR=1.7, 95% CI, 1.0, 3.0) for women in the highest tertile (> 4 pg/mL) of IL-6 compared to those in the lowest tertile (<1.8 pg/mL). The association with IL6 was stronger after 4 years of follow-up (OR=2.6, 95% CI, 1.0, 6.7 for highest vs. lowest tertile) compared to an OR of 1.4 (0.7, 2.9) for those diagnosed within 1–4 years of follow-up. No associations were observed with the other examined pro-inflammatory cytokines, IL1β, IL8 and TNFα.
Systemic plasma IL6 levels may inform long-term gastric cancer risk. This novel finding awaits confirmation in future studies with sequential plasma collection.
cytokine; gastric cancer; prediagnostic
Accumulating evidence suggests an etiologic role in renal cell carcinoma (RCC) for physical activity. However, it is unknown if prolonged sitting, which is thought to be distinct from too little moderate-vigorous physical activity, is an independent risk factor for RCC. The authors prospectively examined the relationship of prolonged sitting and risk of RCC among 289,512 women and men in the National Institutes of Health—AARP Diet and Health Study.
From 1996 through 2006, 1206 invasive RCC cancer cases were identified. Cox proportional hazards regression was used to estimate multivariate hazard ratios (HR) and 95% confidence intervals (CI).
After controlling for known risk factors for RCC, we did not find evidence of associations between RCC risk and time spent per day sitting while watching television or videos (HR7+hrs:<1 hr: 0.96 (0.66, 1.38), ptrend=0.707) or total sitting time (HR9+hrs: <3hrs: 1.11 (0.87, 1.41), ptrend=0.765).
Prolonged sitting time was not associated with RCC risk among men and women in this large cohort.
sedentary lifestyle; kidney neoplasms; cohort studies
Renal cell carcinoma (RCC) incidence is higher among blacks than whites in the United States, and has been associated with the frequency and timing of childbirth among women in some epidemiologic studies. We investigated whether reproductive factors are associated with RCC, overall and by race, within a population-based case-control study.
Between 2002 and 2007, 497 female cases of incident RCC (136 black, 361 white) and 546 female controls (273 black, 273 white) within the Detroit and Chicago metropolitan areas were enrolled. Information on reproductive history and other factors was collected through in-person interviews. Multivariate adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression.
Reduced RCC risk was observed among women aged ≥30 years at first live birth, relative to an age of <20 years (OR 0.5, 95% CI 0.3–0.9). This association was present among both white (OR 0.4, 95% CI 0.2–0.9) and, though not statistically significant, black women (OR 0.6, 95% CI 0.2–1.8). In analyses restricted to clear cell adenocarcinoma, the most common RCC histologic subtype, the association was particularly strong (OR 0.3, 95% CI 0.2–0.8). We did not observe clear evidence of association with RCC for other reproductive factors.
Our findings further support an association between late maternal age at first birth and reduced RCC risk, and suggest that the association may be particularly strong for clear cell adenocarcinoma.
Renal cell carcinoma; reproductive factors; case-control studies; hysterectomy; parity
We assessed the influence of tumor size and surgical approach on the use of lymphadenectomy and adrenalectomy with radical nephrectomy.
We evaluated patients with renal cell carcinoma (RCC) enrolled in the US Kidney Cancer Study, a case–control study in the metropolitan areas of Detroit and Chicago from 2002–2007. We identified patients who underwent open (ORN) or laparoscopic radical nephrectomy (LRN). We used medical records and SEER data to determine the proportion of patients who underwent lymphadenectomy or adrenalectomy. Bivariate analyses were performed to evaluate associations between tumor size, surgical approach, and receipt of lymphadenectomy or adrenalectomy.
We identified 730 patients who underwent ORN (427, 58%) or LRN (303, 42%) for RCC from 2002–2007. Among this group, 11% and 24% underwent lymphadenectomy or adrenalectomy, respectively. Lymphadenectomy was more common among patients treated from an open surgical approach (14.1% ORN vs 5.9% LRN, p<0.01); this difference was most pronounced for cases with tumors between 4–7 cm (15.9% vs 2.9%, p=0.01). Patients treated with ORN were also more likely to undergo adrenalectomy, with the greatest discrepancy among cases with tumors ≤ 4 cm (21.7% vs. 11.4%, p<0.01).
Among patients undergoing radical nephrectomy for RCC, the use of lymphadenectomy and adrenalectomy is relatively uncommon and varies by tumor size and surgical approach. With an increasing number of patients with small tumors, the diffusion of laparoscopy, and the emergence of clinical trials evaluating systemic adjuvant therapies, our findings highlight important considerations for optimizing surgical management of patients with RCC.
lymph node excision; adrenalectomy; carcinoma; renal cell; laparoscopy; neoplasm staging
Background and aims
Alcohol intake is a strong and well-established risk factor for esophageal squamous cell carcinoma (ESCC), but the association with esophageal adenocarcinoma (EA) or adjacent tumors of the esophagogastric junction (EGJA), remains unclear. Therefore, we determined the association of alcohol intake with ESCC, EA, and EGJA in nine case-control studies and two cohort studies of the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON).
Materials and methods
We collected information on alcohol intake, age, sex, education, body mass index, gastroesophageal reflux, and tobacco smoking from each study. Along with 10,854 controls, 1,821 EA, and 1,837 EGJA, seven studies also collected ESCC cases (n=1,016). Study-specific odds ratios (OR) and 95% confidence intervals (CI) were calculated from multivariate-adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models.
We observed no increase in risk of EA or EGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category (≥7 drinks per day) were 0.97 (95% CI = 0.68-1.36) for EA and 0.77 (95% CI = 0.54-1.10) for EGJA. Suggestive findings linked moderate intake (e.g. 0.5 to <1 drinks per day) to decreased risk of EA (OR = 0.63 95% CI = 0.41-0.99) and EGJA (OR = 0.78; 95% CI = 0.62-0.99). In contrast, alcohol intake was strongly associated with increased risk of ESCC (OR for ≥7 drinks per day= 9.62, 95%CI=4.26-21.71).
In contrast to ESCC, higher alcohol consumption was not associated with increased risk of either EA or EGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies.
Alcohol Drinking; Esophageal Neoplasms; Stomach Neoplasms; Epidemiology
Mitochondrial DNA (mtDNA) are approximately 16,000bp circular double-stranded DNA molecules that are prime targets of oxidative damage. Several somatic mutations in mtDNA have been observed in gastric tumors suggesting an involvement in gastric cancer risk and progression. mtDNA copy number in leukocyte DNA has also been linked to several other cancers, although the temporal relationship between mtDNA and cancer has not been adequately explored.
Using a nested case-control study design, we examined the association between mtDNA copy number in 162 GC cases and 299 matched controls within the Shanghai Women's Health Study, a large population-based prospective cohort. Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay in peripheral leukocytes.
mtDNA copy number levels were comparable among cases and controls, with a median of 1.04 (interquartile range, 0.87–1.25) and 1.06 (interquartile range, 0.88–1.29), respectively. Overall, mtDNA was not associated with GC risk. However, the association differed when stratified by the time between sample collection and cancer diagnosis. An association between low levels of mtDNA copy number (
Conclusions and Impact
Our findings suggest that there is no association between leukocyte mtDNA copy number and risk of GC; however, we observed a possible early disease effect on mtDNA copy number levels.
Mitochondrial DNA copy number; mtDNA; gastric cancer; cohort study
Aside from tobacco carcinogen metabolism, isothiocyanates (ITC) from cruciferous vegetables may induce apoptosis or steroid metabolism to reduce lung cancer risk. To separate the effect of these divergent mechanisms of action, we investigated the association between urinary ITC levels and lung cancer risk among non-smoking women.
We conducted a nested case-control within the Shanghai Women’s Health Study. Subjects included 209 incident lung cancer cases who never used tobacco, and 787 individually matched non-smoking controls. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) summarizing the association between urinary ITC levels and lung cancer. Secondary analyses stratified the ITC-lung cancer analyses by menopausal status, exposure to environmental tobacco smoke, and GSTM1 and GSTT1 genotypes.
Urinary ITC levels were not significantly associated with lower lung cancer risk among non-smoking women, regardless of exposure to environmental tobacco smoke or menopausal status. Furthermore, this association was not modified by GSTT1 genotype. However, an inverse association was suggested among women with a GSTM1-positive genotype (Q1: OR=1.0 (reference); Q2: OR=0.35 (0.14, 0.89); Q3: OR=0.47 (0.20, 1.10); Q4: OR=0.63 (0.35, 1.54), p-trend = 0.38)). In contrast, lung cancer risk was positively associated with urinary ITC levels among women with the GSTM1-null genotype (Q1: OR=1.0 (reference); Q2: OR=1.67 (0.80, 3.50); Q3: OR=1.54 (0.71, 3.33); Q4: OR=2.22 (1.05, 4.67), p-trend = 0.06)).
Urinary ITC levels were not associated overall with lower lung cancer risk among non-smoking women, but secondary analyses suggested an interaction between urinary ITC levels, GSTM1 genotype, and lung cancer risk.
isothiocyanate; lung neoplasm; diet; genetic susceptibility; women
Chronic hepatitis C virus (HCV) infection is an established cause of liver cancer, and recent studies have suggested a link with kidney cancer. The aim of this study was to evaluate risk of kidney cancer in relation to HCV infection in a nationwide registry-based study of Swedish residents diagnosed with HCV between 1990 and 2006. A total of 43,000 patients with chronic HCV infection were included, and the mean follow-up time was 9.3 years. Observed kidney cancer incidence and mortality in the cohort were compared with expected values based on the age- and sex-adjusted rates in the general population. Risk of hospitalization for other chronic kidney disease was also evaluated using Cox proportional hazards regression. No association between HCV infection and risk of kidney cancer was observed [standardized incidence ratio with one-year lag = 1.2; 95% confidence interval (CI) 0.8–1.7]. Risk of hospitalization for non-cancer kidney disease was significantly elevated in the HCV cohort, with significantly stronger associations observed among women than among men [hazard ratio = 5.8 (95% CI 4.2–7.9) and 3.9 (95% CI 3.2–4.8) for women and men, respectively]. Results of this study do not support the hypothesis that chronic HCV infection confers an increased risk of kidney cancer. However, we did find an association between HCV infection and chronic kidney disease, particularly among women. Given inconsistent findings in the literature, it is premature to consider HCV infection to be a risk factor for kidney cancer.
chronic hepatitis C virus infection; renal cell carcinoma; kidney cancer; cancer registry; chronic kidney disease
To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers.
We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression.
PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing GERD/BMI score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA.
PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, while fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.
esophageal adenocarcinoma; gastric cardia adenocarcinoma; esophageal squamous cell carcinoma; diet; principal components
Results 1-25 (105)
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