Use of oral contraceptives,intrauterine devices and tubal sterilization and cancer risk in a large prospective study,from 1996 to 2006

The association of contraceptive methods, including oral contraceptives (OC), intrauterine devices (IUD) and tubal sterilization (TS), with overall and site‐specific cancer were prospectively investigated in a cohort of 66,661 Chinese women in Shanghai, 76.7% of whom used contraception. During a median follow‐up time of 7.5 years, 2,250 women were diagnosed with cancer. Ever‐use of any contraceptive method was not associated with overall cancer risk [adjusted hazard ratio (HR_adj) = 1.02, 95% CI, 0.92–1.12]. Use of any contraceptive method was associated with increased risk of rectal cancer (HR_adj = 1.68, 95% CI, 1.08–2.62) and reduced risk of thyroid cancer (HR_adj = 0.63, 95% CI, 0.38–1.04). Risk of gallbladder cancer increased with ever use of OC (HR_adj = 2.38, 95% CI, 1.26–4.49). IUD use was associated with a possible reduced risk of thyroid cancer (HR_adj = 0.64, 95% CI, 0.38–1.07). Longer duration of IUD use decreased risk for breast, thyroid and lung cancers. Ever having a TS was associated with increased uterine body cancer (HR_adj = 2.50, 95% CI, 1.47–4.25) and decreased risk of stomach cancer (HR_adj = 0.59, 95% CI, 0.39–0.91). We did not find any contraceptive method to be related to the risk of ovarian cancer but the analyses were based on few events. Although chance findings are a likely explanation for some of the associations found in our study, these findings suggest that various contraceptive methods or reproductive patterns may play a role in the etiology of cancer. © 2008 Wiley‐Liss, Inc.     

Menopausal hormone therapy use and risk of primary liver cancer in the clinical practice research datalink

Primary liver cancer occurs less commonly among women than men in almost all countries. This discrepancy has suggested that hormone levels and/or exogenous hormone use could have an effect on risk, although prior studies have reached inconsistent conclusions. Thus, the current study was conducted to examine the relationship between menopausal hormone therapy (MHT) use and development of liver cancer. A nested case‐control study was conducted within the United Kingdom's Clinical Practice Research Datalink (CPRD). Controls were matched, at a 4‐to‐1 ratio, to women diagnosed with primary liver cancer between 1988 and 2011. A second match, based on whether the cases and controls had diabetes, was also conducted. Odds ratios (OR) and 95% confidence intervals (95%CI) for associations of MHT with liver cancer were estimated using conditional logistic regression adjusted for known risk factors. In the overall match, 339 women with liver cancer were matched to 1318 controls. MHT use was associated with a significantly lower risk of liver cancer (OR_adj = 0.58, 95%CI = 0.37–0.90) especially among users of estrogen‐only MHT (OR_adj = 0.44, 95%CI = 0.22–0.88) and among past users (OR_adj = 0.53, 95%CI = 0.32–0.88). Among the matched cases (n = 58) and controls (n = 232) with diabetes, the odds ratios were similar to the overall analysis (OR_adj = 0.57, 95%CI = 0.09–3.53), but did not attain statistical significance. In the current study, MHT use, especially estrogen‐only MHT use, was associated with a significantly lower risk of liver cancer. These results support the need of further investigation into whether hormonal etiologies can explain the variation in liver cancer incidence between men and women.     

Independent and joint associations of blood lipids and lipoproteins with lung cancer risk in Chinese males: A prospective cohort study

To investigate the independent and joint associations of blood lipids and lipoproteins with lung cancer risk in Chinese males, a prospective cohort study was conducted. A total of 109,798 males with baseline information on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and non-HDL were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a 9-year follow-up, a total of 986 lung cancer cases were identified. Multivariable analyses showed that both males with low TC (HR_Q1vs.Q2 = 1.27, 95%CI: 1.02–1.60) and males with high TC (HR_Q5vs.Q2 = 1.30, 95%CI: 1.04–1.63) had an increased lung cancer risk, and the U-shaped association was also revealed in the RCS analysis (p_overall = 0.013, p_nonlinear = 0.006). Furthermore, both low TG (HR_Q1vs.Q2 = 1.24, 95%CI: 0.99–1.54) and high TG (HR_Q5vs.Q2 = 1.27, 95%CI: 1.01–1.59) were associated with increased lung cancer risk, while low LDL-C (HR_Q1vs.Q2 = 1.38, 95%CI: 1.11–1.72) was associated with increased lung cancer risk. When TC, TG and LDL-C were considered jointly, the number of abnormal indicators was linearly associated with an increased risk of lung cancer (p_trend < 0.001), as subjects with three abnormal indicators had a twofold higher risk of developing lung cancer (HR = 2.02, 95%CI: 1.62–2.54). Notably, these associations were statistically significant among never smokers, never drinkers and overweight/obese males. These findings suggest that dyslipidemia may potentially be a modifiable risk factor that has key scientific and clinical significance for lung cancer prevention.     

Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HR_fixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HR_fixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HR_fixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HR_fixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.     

Risk Factors for Rectal Cancer and Methylenetetrahydrofolate Reductase Polymorphisms in a Population in Northeast Thailand

Background and Aim: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) are known to beassociated with predisposition for certain cancers. This study aimed to evaluate the effects of lifestyle factors,family history and genetic polymorphisms in MTHFR C677T and A1298C on rectal cancer risk and possibleinteractions with lifestyle factors in Northeast Thailand. Methods: A hospital-based case-control study wasconducted during 2002-2006 with recruitment of 112 rectal cancer cases and 242 non-rectal cancer patient controls.Information was collected using a structured-questionnaire. Blood samples were obtained for assay of MTHFRC677T and A1298C genotypes by polymerase chain reaction with restriction fragment length polymorphism(PCR-RFLP) techniques. Associations between lifestyle factors, family history and genetic polymorphisms v.s.rectal cancer risk were assessed using logistic regression analysis. Results: Subjects with frequent and occasionalconstipation had a higher risk (OR_adj.=14.64; 95%CI=4.28-50.04 and OR_adj.=2.15; 95%CI=1.14-4.06), along withthose who reported ever having hemorrhoids (OR_adj.=2.82; 95%CI=1.36-5.84) or a family history of cancer(OR_adj.=1.90; 95%CI=1.06-3.39). Consumption of a high level of pork was also associated with risk (OR_adj.=1.82;95%CI=1.05-3.15). Interactions were not observed between MTHFR and other risk factors. Conclusions: Thisstudy suggested that the risk factors for rectal cancer in the Thai population are bowel habits, having hadhemorrhoids, a family history of cancer and pork consumption.     

The prognostic impact of COX‐2 expression in breast cancer depends on oral contraceptive history,preoperative NSAID use,and tumor size

The association between tumor cyclooxygenase 2 (COX‐2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX‐2 tumor expression according to adjuvant treatment, and potential effect modifications of non‐steroid anti‐inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002‐2012 was followed until June 2014 (median 5 years). Tumor‐specific COX‐2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX‐2 intensity (negative, weak‐moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor‐specific COX‐2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX‐2 expression was associated with lower risk for breast cancer events during the first five years of follow‐up, _adjHR 0.60 (95%CI: 0.37‐0.97), per category. The association between COX‐2 expression and prognosis was significantly modified by oral contraceptive (OC) use (P_interaction = 0.048), preoperative NSAID use (P_interaction = 0.009), and tumor size (P_interaction = 0.039). COX‐2 negativity was associated with increased risk for events during the first five years in ever OC users, _adjHR 1.94 (1.01‐3.72) and during the 11‐year follow‐up in preoperative NSAID users, _adjHR 4.51 (1.18‐11.44) as well as in patients with large tumors, _adjHR 2.57 (1.28‐5.15). In conclusion, this study, one of the largest evaluating COX‐2 expression in breast cancer, indicates that the prognostic impact of COX‐2 expression depends on host factors and tumor characteristics.     

The association between individual metabolic syndrome components,primary liver cancer and cirrhosis: A study in the Swedish AMORIS cohort

Metabolic syndrome (MetS) is associated with non‐alcoholic fatty liver disease, which may progress to cirrhosis, a significant risk factor of hepatocellular carcinoma (HCC), the commonest malignant primary liver cancer (PLC). We investigated the association between the individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity), PLC and cirrhosis. A total of 509,436 participants from the Swedish AMORIS cohort, recruited between January 1985 and December 1996 (end‐date December 2011), aged ≥20 with baseline triglycerides (TG), total cholesterol (TC), glucose and liver enzymes were included. Those with baseline benign liver tumours, PLC or cirrhosis were excluded. Multivariate Cox regression, adjusted for age, gender, socio‐economic status, liver disease (excluding cirrhosis) and MetS factors were used to estimate the association with PLC and cirrhosis. There were 766 PLC and 2,775 cirrhosis cases over 13 years. Raised TG, low TC, raised glucose, diabetes and low HDL were associated with an increased risk of developing PLC and cirrhosis. ApoB/ApoA‐I ratio were also associated with PLC, whilst low LDL, raised TG/HDL, low ApoA‐I and low ApoB were associated with cirrhosis. Obesity was significantly associated with PLC but not cirrhosis. Raised TG, low TC, raised glucose and diabetes showed stronger associations with PLC in participants with cirrhosis but many participants developed PLC without cirrhosis. Individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity) were associated with an increased risk of developing PLC or cirrhosis. MetS components were more strongly associated with PLC with preceding cirrhosis history but many participants developed PLC without cirrhosis.     

Association between metformin use after surgery for colorectal cancer and oncological outcomes: A nationwide register‐based study

Colorectal cancer is one of the most common malignancies in the Western world, and even after surgical removal, there is a high recurrence rate. Metformin treatment has been associated with a reduced risk of developing cancer, but whether metformin influences the risk of recurrence is unknown. The aim of our study was to examine the association between treatment with metformin and recurrence‐free, disease‐free survival and all‐cause mortality after surgery for colorectal cancer. The study was an observational register‐based study and included 25,785 patients, of which 1,116 had medically treated diabetes and 966 started metformin treatment at some point postoperatively. Diabetes was not associated with neither disease‐free (HR_adjusted = 1.09, 95% CI 0.97–1.21, p = 0.15) nor recurrence‐free survival (HR_adjusted = 1.13, 95% CI 0.95–1.35, p = 0.17). The study found no difference in regards to disease‐free or recurrence‐free survival between the metformin treated group (HR_RFS = 1.06, 95% CI 0.87–1.15, p = 0.57, HR_DFS = 1.01, 95% CI 0.89–1.15, p = 0.85) and non‐diabetic patients. Patients with diabetes had increased all‐cause mortality (HR_adjusted = 1.29, 95% CI 1.16–1.45, p < 0.0001). Metformin treatment did not affect all‐cause mortality (HR = 1.07, 95% CI 0.94–1.22, p = 0.33) compared to non‐diabetic patients. In conclusion, our study did not find an association between diabetes or metformin treatment and recurrence‐free or disease‐free survival after surgery for colorectal cancer. However, diagnosis of diabetes is associated with increased all‐cause mortality.     

Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: A nested case‐control study in nonsmoking postmenopausal women from the EPIC cohort

Acrylamide, classified in 1994 by IARC as “probably carcinogenic to humans,” was discovered in 2002 in some heat‐treated, carbohydrate‐rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case‐control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non‐smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type‐I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HR_HbAA;Q5vsQ1: 0.84, 95%CI: 0.49–1.48; HR_HbGA;Q5vsQ1: 0.94, 95%CI: 0.54–1.63) or type‐I EC risk. Additionally, none of the subgroups investigated (BMI < 25 vs. ≥25 kg m^?2, alcohol drinkers vs. never drinkers, oral contraceptive users vs. non‐users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type‐I EC risk in 768 nonsmoking postmenopausal women from the EPIC cohort.     

Association of breast cancer risk loci with breast cancer survival

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over‐all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta‐analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1‐rs3817198 was significantly associated with improved OS (HR_per‐allele=0.70; 95% CI: 0.58–0.85; p_trend = 2.84 × 10^?4; HR_{heterozygotes} = 0.71; 95% CI: 0.55–0.92; HR_homozygotes = 0.48; 95% CI: 0.31–0.76; p_2DF = 1.45 × 10^?3). In silico, the C allele of LSP1‐rs3817198 was predicted to increase expression of the tumor suppressor cyclin‐dependent kinase inhibitor 1C (CDKN1C). In the meta‐analysis, TNRC9‐rs3803662 was significantly associated with increased death hazard (HR_META =1.09; 95% CI: 1.04–1.15; p_trend = 6.6 × 10^?4; HR_{heterozygotes} = 0.96 95% CI: 0.90–1.03; HR_homozygotes = 1.21; 95% CI: 1.09–1.35; p_2DF=1.25 × 10^?4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1‐rs3817198 and TNRC9‐rs3803662.     

Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer

While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP‐CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20–1.79, p = 1.68 × 10⁻⁴). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92–1.18, p = 0.49), 0.94 (95% CI: 0.84–1.05, p = 0.27), and 0.98 (95% CI: 0.85–1.12, p = 0.75) respectively. A genetic risk score for 3‐hydoxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR ) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49–0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.     

血脂水平与胆道癌和胆石症关系的病例对照研究

目的：探讨血脂水平与胆道癌、胆石症的关系。方法：采用全人群病例对照研究方法，对上海市区462例胆道癌、982例胆石症和808例人群对照进行六项血脂指标的检测，采用多样本比较的秩和检验方法分析血脂水平与胆道癌和胆石症的关系。结果：男性胆石症层中，胆道癌患者TG的含量高于胆石症患者和人群对照；且各部位胆石症和胆道癌患者HDL的含量均低于人群对照。男性非胆石症层中，胆道癌患者TG和ApoB的含量显著高于人群对照，而TC、HDL、LDL和ApoA的水平则低于人群对照。在女性胆石症层中。胆道癌、胆石症患者和人群对照HDL、ApoA的平均含量由高到低分别为人群对照、胆石症和胆道癌患者。女性非胆石症层中，胆道癌患者HDL和ApoA的平均含量均显著低于人群对照。结论：男女性胆道癌和胆石症患者都存在脂质代谢异常，胆道癌患者TG水平高于对照和胆石症患者．而HDL水平则低于对照和胆石症患者。     

Improvement in population‐based survival of stage IV NSCLC due to increased use of chemotherapy

This study aimed to investigate which factors were associated with the administration of chemotherapy for patients with stage IV non‐small cell lung cancer (NSCLC), and their relation to survival at a population‐based level. All patients with NSCLC stage IV from 2001 to 2012 were identified in the Netherlands Cancer Registry in the Eindhoven area (n = 5,428). Chemotherapy use and survival were evaluated by logistic and Cox regression analyses, respectively. The proportion of patients receiving chemotherapy increased from 30% in 2001 to 48% in 2012. Higher rates were found among younger patients [multivariable odds ratio (OR_{≤64_vs._≥75_years}): 1.8 (95%CI 1.6–2.1)], high socioeconomic status [OR_{high_vs._low}: 1.8 (95%CI 1.6–2.2)], no comorbidity [OR_{0_vs._≥2}: 1.5 (95%CI 1.3–1.8)], diagnosed in recent years [OR_{2010–2012_vs._2001–2003}: 2.0 (95%CI 1.6–2.3)] and adenocarcinoma [OR_{squamous_vs._adenocarcinoma}: 0.8 (95%CI 0.6–0.9)]. Having liver metastasis was associated with reduced odds (OR_{liver_vs._brain}: 0.8 (95%CI 0.7–1.0). The variation between hospitals was large, up to OR 2.0 (95%CI 1.5–2.6). Median survival increased from 18 weeks in 2001–2003 to 21 weeks in 2010–2012 (log‐rank p = 0.007), and was 35 weeks in patients with and 10 weeks without chemotherapy. The multivariable hazard of death reduced significantly over time [HR_{2001–2003_vs._2010–2012}: 1.1 (95%CI 1.0–1.2), HR_{2004–2005_vs._2010–2012}: 1.2 (95%CI 1.1–1.3)] and only remained significant for 2004–2006 after additional adjustment for chemotherapy [final multivariable model, HR_{2004–2006_vs._2010–2012}: 1.1 (95%CI 1.0–1.2)]. Besides, prognostic factors were having chemotherapy [final multivariable model: HR 0.4 (95%CI 0.4–0.4)], female sex [HR_{male_vs._female}: 1.1 (95%CI 1.0–1.1)], socioeconomic status [HR_{intermediate_and_high_vs._low} both 0.9 (95%CI 0.9–1.0)], comorbidity [HR_{unknown_vs._≥2}: 1.3 (95%CI 1.2–1.5)], histology [HR_{other_vs._adenocarcinoma}: 1.1 (95%CI 1.1–1.2)], and location of metastasis [range: 1.2 (HR_{lymph_nodes_vs._brain}) ? 1.6 (HR_{liver_vs._brain})]. In conclusion, population‐based survival increased due to increasing administration rates of chemotherapy. The administration of chemotherapy was affected by hospital of diagnosis and both patient and tumour characteristics. Identifying patients who benefit from chemotherapy should become a key issue.     

Red and processed meat intake and cancer risk: Results from the prospective NutriNet‐Santé cohort study

The International Agency for Research on Cancer (WHO‐IARC) classified red meat and processed meat as probably carcinogenic and carcinogenic for humans, respectively. These conclusions were mainly based on studies concerning colorectal cancer, but scientific evidence is still limited for other cancer locations. In this study, we investigated the prospective associations between red and processed meat intakes and overall, breast, and prostate cancer risk. This prospective study included 61,476 men and women of the French NutriNet‐Santé cohort (2009–2015) aged ≥35 y and who completed at least three 24 hrs dietary records during the first year of follow‐up. The risk of developing cancer was compared across sex‐specific quintiles of red and processed meat intakes by multivariable Cox models. 1,609 first primary incident cancer cases were diagnosed during follow‐up, among which 544 breast cancers and 222 prostate cancers. Red meat intake was associated with increased risk of overall cancers [HR_Q5vs.Q1=1.31 (1.10–1.55), p_trend = 0.01) and breast cancer (HR_Q5vs.Q1 = 1.83 (1.33–2.51), p_trend = 0.002]. The latter association was observed in both premenopausal [HR_Q5vs.Q1=2.04 (1.03–4.06)] and postmenopausal women [HR_Q5vs.Q1=1.79 (1.26‐2.55)]. No association was observed between red meat intake and prostate cancer risk. Processed meat intake was relatively low in this study (cut‐offs for the 5th quintile = 46 g/d in men and 29 g/d in women) and was not associated with overall, breast or prostate cancer risk. This large cohort study suggested that red meat may be involved carcinogenesis at several cancer locations (other than colon‐rectum), in particular breast cancer. These results are consistent with mechanistic evidence from experimental studies.     

Inflammatory potential of diet and risk of pancreatic cancer in the Prostate,Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial

Inflammation plays a central role in pancreatic cancer etiology and can be modulated by diet. We aimed to examine the association between the inflammatory potential of diet, assessed with the Dietary Inflammatory Index (DII®), and pancreatic cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial prospective cohort. Our study included 101,449 participants aged 52–78 years at baseline who completed both baseline questionnaire and a diet history questionnaire. Energy‐adjusted DII (E‐DII) scores were computed based on food and supplement intake. Cox proportional hazards models and time dependent Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with participants in the lowest E‐DII quintile (most anti‐inflammatory scores) as referent. After a median 8.5 years of follow‐up, 328 pancreatic cancer cases were identified. E‐DII scores were not associated with pancreatic cancer risk in the multivariable model (HR_Q5vsQ1 = 0.94; 95% CI = 0.66–1.35; p‐trend = 0.43). Time significantly modified the association (p‐interaction = 0.01). During follow up <4 years, there was suggestive evidence of an inverse association between E‐DII and pancreatic cancer (HR_Q5vsQ1 = 0.60; 95% CI = 0.35–1.02; p‐trend = 0.20) while there was a significant positive trend in the follow up ≥4 years (HR_Q5vsQ1 = 1.31; 95% CI = 0.83–2.08; p‐trend = 0.03). Similar results were observed for E‐DII from food only. Our study does not support an association between inflammatory potential of diet and pancreatic cancer risk; however, heterogeneous results were obtained with different follow‐up times. These divergent associations may result from the influences of undetected disease in the short‐term.     

Active cigarette smoking and risk of breast cancer

Although epidemiological evidence on the role of active cigarette smoking in breast cancer risk has been inconsistent, recent literature supports a modest association between smoking and breast cancer. This association is particularly observed in women who smoke for a long duration, or who smoke for a long time prior to their first pregnancy. Here, we provide updated results on cigarette smoking and breast cancer risk in the Canadian National Breast Screening Study (NBSS). The NBSS is a large cohort of 89,835 women, aged 40–59, who were followed for a mean of 22.1 years, resulting in the ascertainment of 6,549 incident cases of breast cancer. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cigarette smoking variables with breast cancer risk. We found breast cancer to be associated with duration (40 years vs. 0: HR = 1.57; 95%CI = 1.29–1.92), intensity (40 cigarettes per day vs. 0: HR = 1.21; 95%CI = 1.04–1.40), cumulative exposure (40 pack‐years vs. 0: HR = 1.19; 95%CI = 1.06–1.13) and latency (40 years since initiation vs. 0: HR = 1.19; 95%CI = 1.10–1.53) of cigarette smoking. Number of years smoked prior to first full‐term pregnancy was associated with higher risk of breast cancer than comparative years smoked post‐pregnancy (among parous women, 5 years pre pregnancy vs. 0: HR = 1.18; 95%CI = 1.10–1.26). These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.     

Risks of cancer among a cohort of 23,935 men and women with osteoporosis

Low hormone levels among persons with osteoporosis may decrease risk of some cancers. Other osteoporosis risk factors, such as smoking and alcohol consumption, however, may increase risk. As these deleterious factors are more often associated with osteoporosis diagnosed prior to age 70 years, cancer risk may be higher in these younger persons than in the general population. To examine this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were identified in the Danish Inpatient Register. Linkage to the Danish Cancer Registry identified all cancer outcomes through 2003. Standardized incidence ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare cancer incidence in the cohort with that in the general population. Persons diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11, 95%CI = 1.04-1.19; men: SIR = 1.31, 95%CI = 1.13-1.50) due, in part, to increased risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung. Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91, 95%CI = 0.87-0.96; men: SIR = 0.89, 0.77-1.01) due, in part, to decreased risks of breast, endometrial, colon, rectal and brain cancers in women and prostate cancer in men. These results suggest that risk factors associated with earlier onset osteoporosis may be associated with increased risk of cancer. Conversely, factors associated with later onset osteoporosis may be related to a decreased risk of cancer.     

Ingested nitrate and nitrite,disinfection by‐products,and pancreatic cancer risk in postmenopausal women

Nitrate and nitrite are precursors of N‐nitroso compounds (NOC), probable human carcinogens that cause pancreatic tumors in animals. Disinfection by‐products (DBP) exposures have also been linked with digestive system cancers, but few studies have evaluated relationships with pancreatic cancer. We investigated the association of pancreatic cancer with these drinking water contaminants and dietary nitrate/nitrite in a cohort of postmenopausal women in Iowa (1986–2011). We used historical monitoring and treatment data to estimate levels of long‐term average nitrate and total trihalomethanes (TTHM; the sum of the most prevalent DBP class) and the duration exceeding one‐half the maximum contaminant level (>½ MCL; 5 mg/L nitrate‐nitrogen, 40 µg/L TTHM) among participants on public water supplies (PWS) >10 years. We estimated dietary nitrate and nitrite intakes using a food frequency questionnaire. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression and evaluated nitrate interactions with smoking and vitamin C intake. We identified 313 cases among 34,242 women, including 152 with >10 years PWS use (N = 15,710). Multivariable models of average nitrate showed no association with pancreatic cancer (HR_{p95 vs. Q1} = 1.16, 95% CI: 0.51–2.64). Associations with average TTHM levels were also null (HR_{Q4 vs. Q1} = 0.70, 95% CI:0.42–1.18). We observed no trend with increasing years of exposure to either contaminant at levels >½ MCL. Positive associations were suggested in the highest dietary nitrite intake from processed meat (HR_{p95 vs. Q1} = 1.66, 95% CI 1.00–2.75;p_trend = 0.05). We found no interactions of nitrate with known modifiers of endogenous NOC formation. Our results suggest that nitrite intake from processed meat may be a risk factor for pancreatic cancer.     

No effect of meat,meat cooking preferences,meat mutagens or heme iron on lung cancer risk in the prostate,lung, colorectal and ovarian cancer screening trial

Recent epidemiological studies have suggested that red and processed meat may increase the risk of lung cancer. Possible underlying mechanisms include mutagens produced during high‐temperature cooking or preservation, or formed endogenously from heme iron in meat. We used data from 99,579 participants of both screened and nonscreened arms of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, aged 55–74 years, to investigate whether meat type, cooking method, doneness level, intake of specific meat mutagens 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline] (DiMeIQx), 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and benzo(a)pyrene (B(a)P)] and heme iron are associated with lung cancer. Participants' diet was assessed prospectively using a 124‐item food frequency questionnaire and an additional meat‐cooking module. Dietary data were used in conjunction with a database to estimate intake of MeIQx, DiMeIQx, PhIP, B(a)P and heme iron. After up to 8 years of follow‐up, 782 incident lung cancer cases were ascertained. Lung cancer risk was not associated with the consumption of either red (men: HR_{Q5 vs. Q1} = 1.11, 95% CI = 0.79–1.56, P_trend = 0.42; women: HR_{Q5 vs. Q1} = 1.30, 95% CI = 0.87–1.95, P_trend = 0.65) or processed meat (men: HR_{Q5 vs. Q1} = 1.12, 95% CI = 0.83–1.53, P_trend = 0.22; women: HR_{Q5 vs. Q1} = 0.98, 95% CI = 0.68–1.41, P_trend = 0.32) in multivariable models. High‐temperature cooking methods, level of meat doneness, meat mutagens and heme iron had no effect on lung cancer risk. In this population, we found no association between meat type, cooking method, doneness level or intake of specific meat mutagens or heme iron and lung cancer risk.     

Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C‐reactive protein, interleukin (IL)‐6, IL‐10 and tumor necrosis factor (TNF)‐α and the risk of TC. A case‐control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer‐free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (OR_T3vs.T1 = 0.69, 95% CI: 0.49–0.98, P_trend = 0.04) but not among men (OR_T3vs.T1 = 1.36, 95% CI: 0.67–2.76, P_trend = 0.37). Increasing levels of IL‐10 were positively associated with TC risk in both genders and significantly so in women (OR_T3vs.T1 = 1.59, 95% CI: 1.13–2.25, P_trend = 0.01) but not in men (OR_T3vs.T1 = 1.78, 95% CI: 0.80–3.98, P_trend = 0.17). Leptin, CRP, IL‐6 and TNF‐α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL‐10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.