Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Stratification of lung adenocarcinoma patients for d-limonene intervention based on the expression signature genes.

Globally, lung cancer ranks as the most lethal malignant neoplasm. d-Limonene, a plant extract enriched with essential oils, has been reported to exert anti-cancer effects both in vitro and in vivo; however, its clinical effect on humans remains elusive. Therefore, the present study aimed to investigate the gene expression signature that would potentially stratify lung adenocarcinoma (LUAD) patients who may benefit from d-limonene intervention, thus facilitating the development of newer treatment strategies for LUAD. In total, 1877 significant differentially expressed genes (DEGs) were identified. These genes were mainly associated with the metabolism of terpenoids and polyketides, lipid metabolism, endocrine system, carbohydrate metabolism, and cell growth and death pathways. Three genes, including antioncogenes FZD3 and MTURN, and oncogene PRC1, which were regulated by d-limonene were identified based on survival analysis of TCGA-LUAD data and were validated by both in vitro and in vivo experiments. High-risk patients screened by the model exhibited a significantly poor prognosis. In conclusion, three gene expression signatures (FZD3, MTURN, and PRC1) were validated by both in vitro and in vivo experiments and identified to help stratify candidate lung adenocarcinoma patients who may benefit from d-limonene intervention. Although further studies are warranted, this study highlighted a potential strategy to improve the treatment outcomes of LUAD patients.

LUAD transcriptomic profile analysis of d-limonene and potential lncRNA chemopreventive target.

d-Limonene, a type of natural extract obtained from citrus oils, was reported to have anti-cancer effects and be well-tolerated by cancer patients. Despite arousing interest as a cancer chemopreventive substance, the transcriptomic profile of d-limonene in humans is poorly understood. Based on the results of the transcriptomic profiling, a lncRNA named protein disulfide isomerase family A member three pseudogene (PDIA3P1) was found to be regulated by d-limonene. PDIA3P1 is an oncogene verified by three lung adenocarcinoma (LUAD) datasets. The knockdown of PDIA3P1 with siRNA decreased the viability, invasion, migration, and proliferation of LUAD cells. Based on The Cancer Genome Atlas (TCGA) LUAD datasets, PDIA3P1 regulates functions and pathways mainly including lipid metabolism, immunity, and the change of the chromosome structure. This study comprehensively performs the transcriptomic analysis of the d-limonene regulation on LUAD, and reveals that PDIA3P1 may be the mediator in helping d-limonene to prevent and suppress LUAD via lipid metabolism, immunity pathway, and the change in the chromosome structure.

SNP rs17079281 decreases lung cancer risk through creating an YY1-binding site to suppress DCBLD1 expression.

Genome-wide association studies (GWAS) have identified numerous genetic variants that are associated with lung cancer risk, but the biological mechanisms underlying these associations remain largely unknown. Here we investigated the functional relevance of a genetic region in 6q22.2 which was identified to be associated with lung cancer risk in our previous GWAS. We performed linkage disequilibrium (LD) analysis and bioinformatic prediction to screen functional SNPs linked to a tagSNP in 6q22.2 loci, followed by two case-control studies and a meta-analysis with 4403 cases and 5336 controls to identify if these functional SNPs were associated with lung cancer risk. A novel SNP rs17079281 in the DCBLD1 promoter was identified to be associated with lung cancer risk in Chinese populations. Compared with those with C allele, patients with T allele had lower risk of adenocarcinoma (adjusted OR = 0.86; 95% CI: 0.80-0.92), but not squamous cell carcinoma (adjusted OR = 0.99; 95% CI: 0.91-1.10), and patients with the C/T or T/T genotype had lower levels of DCBLD1 expression than those with C/C genotype in lung adenocarcinoma tissues. We performed functional assays to characterize its biological relevance. The results showed that the T allele of rs17079281 had higher binding affinity to transcription factor YY1 than the C allele, which suppressed DCBLD1 expression. DCBLD1 behaved like an oncogene, promoting tumor growth by influencing cell cycle progression. These findings suggest that the functional variant rs17079281C>T decreased lung adenocarcinoma risk by creating an YY1-binding site to suppress DCBLD1 expression, which may serve as a biomarker for assessing lung cancer susceptibility.

Genetic Polymorphisms in the Vitamin D Pathway and Non-small Cell Lung Cancer Survival.

Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lung cancer risk. The aim of this study is to assess if genetic polymorphisms in the VD pathway are associated with the prognosis of non-small cell lung cancer (NSCLC). Nine single nucleotide polymorphisms (SNPs) in five genes in the VD pathway were genotyped with the TaqMan assays in 542 patients with primary NSCLC, and the relationships between these SNPs and overall survival were evaluated. We found that SNP rs10741657 in the CYP2R1 gene was associated with the prognosis of NSCLC, especially in elderly patients and not being treated with chemotherapy. Some of the VD pathway-related genetic polymorphisms may influence the prognosis of NSCLC. More research is needed to further confirm the finding and test if VD supplements can be used for NSCLC treatment.

Using a cultural dance program to increase sustainable physical activity for breast cancer survivors-A pilot study.

BACKGROUND: Studies have shown that physical activity can reduce the risk of mortality for female breast cancer patients and improve quality of life, reduce weight, and alter circulating biomarker levels. We conducted a pilot trial to determine the feasibility of increasing physical activity through a cultural dance intervention to achieve similar benefits. METHODS: Conducted a pilot trial implementing a cultural dance intervention to increase and sustain physical activity for breast cancer survivors, which consisted of a six-month group-based intervention of Hula Dance. Anthropometric measures, fasting blood draws, and self-reported questionnaires to assess physical activity, mood, and quality of life, were completed at baseline, at the end of the 6-month intervention (time point month-6), and at two additional post-intervention time points (month-12 and month-24) to assess sustainability. RESULTS: A total of 11 women with a median age of 63 years were enrolled in the intervention trial. Eight of the 11 (73%) completed the trial to month-12 and demonstrated an overall significant increase in weekly moderate exercise. There were no significant changes in intra-individual body mass index (BMI). However, there was a sustained post-intervention reduction in waist circumference and significant changes in circulating biomarker levels. For the self-reported measures, there was a significant increase in vigor/activity (p < 0.001; Profile of Mood States-Short Form). CONCLUSION: Our intervention pilot trial demonstrated that a cultural dance program could achieve a sustainable increase in physical activity for breast cancer survivors, with potential to improve quality of life, increase vigor, and decrease levels of circulating cytokines associated with obesity and inflammation.

Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case-control study.

PURPOSE: Animal and laboratory studies suggest that long-chain omega-3 (n-3) fatty acids, a type of polyunsaturated fat found in fatty fish, may protect against carcinogenesis, but human studies on dietary intake of polyunsaturated fats and fish with endometrial cancer risk show mixed results. METHODS: We evaluated the associations between endometrial cancer risk and intake of fatty acids and fish in a population-based sample of 556 incident cancer cases and 533 age-matched controls using multivariate unconditional logistic regression methods. RESULTS: Although total n-3 fatty acid intake was not associated with endometrial cancer risk, higher intakes of eicosapentaenoic (EPA 20:5) and docosahexaenoic (DHA 22:6) fatty acids were significantly associated with lower risks (OR = 0.57, 95 % CI: 0.39-0.84; OR = 0.64, 95 % CI: 0.44-0.94; respectively) comparing extreme quartiles. The ratio of n-3:n-6 fatty acids was inversely associated with risk only on a continuous scale (OR = 0.84, 95 % CI: 0.71-0.99), while total fish intake was not associated with risk. Fish oil supplement use was significantly associated with reduced risk of endometrial cancer: OR = 0.63 (95 % CI: 0.45-0.88). CONCLUSIONS: Our results suggest that dietary intake of the long-chain polyunsaturated fatty acids EPA and DHA in foods and supplements may have protective associations against the development of endometrial cancer.

Green tea drinking and risk of pancreatic cancer: a large-scale, population-based case-control study in urban Shanghai.

BACKGROUND: Little is known about the etiology of pancreatic cancer. Epidemiological studies on tea consumption and pancreatic cancer risk have been inconclusive. The purpose of the present study was to investigate the association between green tea drinking and the risk of pancreatic cancer in urban Shanghai, China. METHODS: In this population-based case-control study conducted in urban Shanghai, 908 cases of pancreatic cancer and 1067 healthy controls were recruited. Information on tea drinking, including type of tea, amount of tea consumption, temperature of tea, and the duration of regular tea drinking, were collected via interview questionnaire. RESULTS: We examined the association of multiple tea drinking habits with the risk of pancreatic cancer. In women, regular green tea drinking was associated with 32% reduction of pancreatic cancer risk (OR 0.68, 95% CI 0.48-0.96), compared to those who did not drink tea regularly. Increased consumption and longer duration of tea drinking were both associated with reduced pancreatic cancer risk in women. Among regular tea drinkers, lower temperature of tea was associated with reduced risk of pancreatic cancer in both men and women, independent of amount or duration of tea drinking. CONCLUSIONS: Habits of green tea drinking, including regular drinking, amount of consumption, persistence of the habit, and tea temperature, may lower pancreatic cancer risk.

Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel.

BACKGROUND: Paclitaxel interacts with microtubules to exert therapeutic effects. Molecules that affect microtubule activity, such as betaIII-tubulin and stathmin, may interfere with the treatment. In this study, the authors analyzed betaIII-tubulin and stathmin expression in ovarian tumors and examined their associations with treatment response and patient survival. METHODS: The study included 178 patients with epithelial ovarian cancer who underwent cytoreductive surgery followed by platinum-based chemotherapy; of these patients, 75 also received paclitaxel. Fresh tumor samples that were collected at surgery were analyzed for messenger RNA expression of betaIII-tubulin and stathmin using real-time polymerase chain reaction analysis. Associations of these molecules with treatment response, disease progression, and overall survival were evaluated. RESULTS: High stathmin expression was associated with worse disease progression-free and overall survival compared with low stathmin expression. This association was independent of patient age, disease stage, tumor grade, histology, and residual tumor size and was observed in patients who received platinum plus paclitaxel, but not in patients who received platinum without paclitaxel, suggesting that stathmin expression in tumor tissue may interfere with paclitaxel treatment. Similar effects were not observed for betaIII-tubulin, although high betaIII-tubulin expression was associated with disease progression among patients who received platinum without paclitaxel. No associations were observed between treatment response and tubulin or stathmin expression. Expression levels of betaIII-tubulin and stathmin were correlated significantly. CONCLUSIONS: High stathmin expression predicted an unfavorable prognosis in patients with ovarian cancer who received paclitaxel and platinum chemotherapy. This finding supports the possibility that stathmin may interfere with paclitaxel treatment, leading to a poor prognosis for patients with ovarian cancer.

Urinary phytoestrogen excretion and breast cancer risk: evaluating potential effect modifiers endogenous estrogens and anthropometrics.

Steroid sex hormones play a central role in breast carcinogenesis. Evidence from in vitro and animal studies suggests that phytoestrogens may inhibit the development of mammary tumors through their role in regulating the synthesis, metabolism, and signal transduction of steroid hormones. In a study of 117 case-control pairs of postmenopausal women in Shanghai, we investigated whether the association between urinary phytoestrogen excretion and breast cancer risk may differ by levels of endogenous steroid sex hormones, sex hormone binding globulin (SHBG), body mass index (BMI), and waist:hip ratio (WHR). Fasting morning blood and urine samples were collected for the analysis of urinary isoflavonoids and mammalian lignans, as well as blood levels of SHBG and selected steroid hormones. For cancer patients, samples were collected before any cancer therapy. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals after adjusting for potential confounding factors. The inverse associations between urinary phytoestrogens and breast cancer risk were found to be more evident among women with a high BMI or WHR than those with a low level of these anthropometric measurements. Although a reduced risk of breast cancer was observed among women with a high excretion rate of urinary isoflavonoids in all of the strata defined by blood SHBG and steroid hormones, the inverse association was more pronounced among women with a high blood concentration of estradiol, a low level of estrone sulfate, or a low level of SHBG. The risks of breast cancer were also reduced with increasing excretion rate of mammalian lignans, although no test for a linear association was statistically significant in stratified analyses. Findings from this study suggest that the potential protective association of phytoestrogens may be modified by BMI, WHR, and blood levels of SHBG, and steroid hormones.