Cancer & Complementary/Alternative Therapies: Literature update (March 2015)

Our current literature update includes

Nutrition, Vitamins and Natural Products

Mind Body

Nutrition, Vitamins and Natural Products

Vitamin E

Christen WG, Glynn RJ, Gaziano JM, Darke AK, Crowley JJ, Goodman PJ, . . . Klein EA. (2015). Age-related cataract in men in the selenium and vitamin e cancer prevention trial eye endpoints study: A randomized clinical trial. JAMA Ophthalmology, 133(1), 17-24. doi: 

IMPORTANCE: Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium.

OBJECTIVE: To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men. DESIGN, SETTING, AND PARTICIPANTS: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study.

INTERVENTIONS: Individual supplements of selenium (200 mug per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-alpha-tocopheryl acetate).

MAIN OUTCOMES AND MEASURES: Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract. RESULTS: During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P=.37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P=.81). Similar results were observed for cataract extraction.

CONCLUSIONS AND RELEVANCE: These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract.

TRIAL REGISTRATION: Identifier: NCT00784225.

Commentary by Jillian Capodice, LAc, SIO Research Committee Member

This was a sub analysis of the SELECT study (originally designed to test vitamin E, and selenium supplementation alone, together or versus placebo on incidence of prostate cancer in men) called the SELECT Eye Endpoints Study (SEE Study). The SEE Study was a voluntary ancillary study that examined the presence of incident cataracts and cataract extraction in the large cohort of generally healthy men (33, 533 men were randomized in the SELECT Study and 11, 267 participated in the SEE Study). Results demonstrated that there were no differences in incident cataracts nor cataract extraction in men taking vitamin E +/- selenium or selenium alone versus placebo respectively. There was a small nonsignificant 9% lower risk of cataract for men in the selenium (=/- vitamin E) or selenium (with or without vitamin E) group, and somewhat higher at 18% when compared to the placebo group. While incidence of the protective effects of vitamin E has been shown in numerous observational studies, seven prospective clinical studies have demonstrated no utility of high dose vitamin E or selenium on the incidence of cataracts in well nourished men and women with the longest follow up time of those collective studies being 8 years. For selenium, only on study analyzing multivitamin use (including selenium) was shown to be associated with a lower risk of cataract incidence in a nutritionally deficient Chinese population.

Li Y, Sen A, Ren J, Askew LM, Sidahmed E, Brenner DE, . . . Djuric Z. (2015). Effects of vitamin E from supplements and diet on colonic alpha- and -tocopherol concentrations in persons at increased colon cancer risk. Nutrition & Cancer, 67(1), 73-81. doi:

The available evidence indicates that -tocopherol has more potential for colon cancer prevention than alpha-tocopherol, but little is known about the effects of foods and supplements on tocopherol levels in human colon. This study randomized 120 subjects at increased colon cancer risk to either a Mediterranean or a Healthy Eating diet for 6 mo. Supplement use was reported by 39% of the subjects, and vitamin E intake from supplements was twofold higher than that from foods. Serum alpha-tocopherol at baseline was positively predicted by dietary intakes of synthetic vitamin E in foods and supplements but not by natural alpha-tocopherol from foods. For serum -tocopherol, dietary -tocopherol was not a predictor, but dietary alpha-tocopherol was a negative predictor. Unlike with serum, the data supported a role for metabolic factors, and not a direct effect of diet, in governing concentrations of both alpha- and -tocopherol in colon. The Mediterranean intervention increased intakes of natural alpha-tocopherol, which is high in nuts, and decreased intakes of -tocopherol, which is low in olive oil. These dietary changes had no significant effects on colon tocopherols. The impact of diet on colon tocopherols therefore appears to be limited.

Wu QJ, Xiang YB, Yang G, Li HL, Lan Q, Gao YT, . . . Fowke JH. (2015). Vitamin E intake and the lung cancer risk among female nonsmokers: A report from the shanghai women's health study. International Journal of Cancer, 136(3), 610-617. doi:

Vitamin E includes several tocopherol isoforms, which may reduce lung cancer risk, but past studies evaluating the association between vitamin E intake and lung cancer risk were inconsistent. We prospectively investigated the associations between tocopherol intake from diet and from supplements with lung cancer risk among 72,829 Chinese female nonsmokers aged 40-70 years and participating in the Shanghai Women's Health Study (SWHS). Dietary and supplement tocopherol exposure was assessed by a validated food-frequency questionnaire at baseline and reassessed for change in intake during follow-up. Cox proportional hazards models with time-dependent covariates were used to calculate multivariate-adjusted hazard ratios (HRs) and 95% confidence interval (CIs) for lung cancer. After 12.02 years of follow-up, 481 women were diagnosed with lung cancer. Total dietary tocopherol was inversely associated with lung cancer risk among women meeting dietary guidelines for adequate intake (AI) of tocopherol (14 mg/day or more: HR: 0.78; 95% CI 0.60-0.99; compared with the category less than AI). The protective association between dietary tocopherol intake and lung cancer was restricted to women exposed to side-stream smoke in the home and workplace [HR=0.53 (0.29-0.97), p-trend=0.04]. In contrast, vitamin E supplement use was associated with increased lung cancer risk (HR: 1.33; 95% CI: 1.01-1.73), more so for lung adenocarcinoma risk (HR: 1.79; 95% CI: 1.23-2.60). In summary, dietary tocopherol intake may reduce the risk of lung cancer among female nonsmokers; however, supplements may increase lung adenocarcinoma risk and requires further investigation.

Vitamin D

Gilbert R, Bonilla C, Metcalfe C, Lewis S, Evans DM, Fraser WD, . . . Martin RM. (2015). Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: A nested case-control study. Cancer Causes & Control, 26(2), 205-218. doi:

PURPOSE: Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer.

METHODS: In a nested case-control study (within the ProtecT trial), we estimated odds ratios and 95 % confidence intervals (CIs) quantifying associations between SNPs and prostate cancer. Subgroup analyses investigated whether associations were stronger in men who had high/low sun exposure [a proxy for 25(OH)D]. We quantified associations of SNPs with stage (T1-T2/T3-T4) and grade (7). Multiple variant scores included SNPs encoding proteins involved in 25(OH)D synthesis and metabolism.

RESULTS: We included 1,275 prostate cancer cases (141 locally advanced, 385 high grades) and 2,062 healthy controls. Vitamin D-binding protein SNPs were associated with prostate cancer (rs4588-A: OR 1.20, CI 1.01, 1.41, p = 0.04; rs7041-T: OR 1.19, CI 1.02, 1.38, p = 0.03). Low 25(OH)D metabolism score was associated with high (vs low) grade (OR 0.76, CI 0.63, 0.93, p = 0.01); there was a similar association of its component variants: rs6013897-A in CYP24A1 (OR 0.78, CI 0.60, 1.01, p = 0.06) and rs10877012-T in CYP27B1 (OR 0.80, CI 0.63, 1.02, p = 0.07). There was no evidence that associations differed by level of sun exposure.

CONCLUSION: We found some evidence that vitamin D pathway SNPs were associated with prostate cancer risk and grade, but not stage. There was no evidence of an association in men with deficient vitamin D (measured by having low sun exposure).

Commentary by Jillian Capodice, SIO Research Committee Member

This was a nested case control study that aimed to examine the association between increased prostate cancer risk, locally advanced or localized disease and low or high grade prostate cancer (PCa) with sixteen single nucleotide polymorphisms (SNPs) demonstrating low levels or increased cellular uptake of total 25(OH)D or 1,25(OH)2D (metabolites of vitamin D). The TNM system was used as the clinical staging system with T1-T2 disease considered localized and T3-T4 disease considered locally advanced. Low-grade tumors were those with a Gleason score of <7 and high grade were >/= Gleason 7. The analysis showed that there was evidence of an association of linked vitamin D-binding proteins (VDBP) SNPs that correlate to low levels of 25(OH)D with prostate cancer risk. However none of the other SNPs were associated with PCa risk nor stage. There was also an association that the metabolism score which indicates decreased 25(OH)D levels was associated with a higher Gleason grade. All other testing did not support that vitamin D SNPs were associated with PCa risk, stage or Gleason grade. This data adds to a number of studies demonstrating either some or no associations between various vitamin D pathway genes and prostate cancer risk and these studies have looked at a number of genes that are thought to predict circulating levels of 25(OH)D. One limitation is that circulating 25(OH)D and 1,25(OH)2D ma not reflect the actual amounts available for use within target tissue. Strengths of the study include the large sample size and genetic randomization approach.

Reimers LL, Crew KD, Bradshaw PT, Santella RM, Steck SE, Sirosh I, . . . Gammon MD. (2015). Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk. Cancer Causes & Control, 26(2), 187-203. doi:

PURPOSE: Studies of vitamin D-pathway genetic variants in relation to cancer risk have been inconsistent. We examined the associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk.

METHODS: In a population-based case-control study of 967 incident breast cancer cases and 993 controls, we genotyped 25 polymorphisms encoding the vitamin D receptor (VDR) gene, 1alpha-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D-binding protein (GC) and measured plasma 25(OH)D. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs).

RESULTS: Among CYP24A1 polymorphisms, rs6068816 was associated with a 72 % reduction in breast cancer risk (TT vs. CC, OR 0.28, 95 % CI 0.10-0.76; p trend = 0.01), but for rs13038432, the 46 % decrease included the null value (GG vs. AA, OR 0.54, 95 % CI 0.17-1.67; p trend = 0.03). Increased risk that included the null value was noted for CYP24A1 rs3787557 (CC vs. TT, OR 1.34, 95 % CI 0.92-1.89). The VDR polymorphism, TaqI (rs731236), was associated with a 26 % risk reduction (TT vs. CC, OR 0.74, 95 % CI 0.56-0.98; p trend = 0.01). For other polymorphisms, ORs were weak and included the null value. The inverse association for plasma 25(OH)D with breast cancer was more pronounced (OR 0.43, 95 % CI 0.27-0.68) among women with the common allele for CYP24A1, rs927650 (p for interaction on a multiplicative scale = 0.01).

CONCLUSION: Breast cancer risk may be associated with specific vitamin D-related polymorphisms, particularly CYP24A1. Genetic variation in the vitamin D pathway should be considered when designing potential intervention strategies with vitamin D supplementation.

Weinstein SJ, Purdue MP, Smith-Warner SA, Mondul AM, Black A, Ahn J, . . . Albanes D. (2015). Serum 25-hydroxyvitamin D, vitamin D binding protein and risk of colorectal cancer in the prostate, lung, colorectal and ovarian cancer screening trial. International Journal of Cancer, 136(6), E654-64. doi:

The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR=0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR=0.82, 95% CI 0.54-1.26, and OR=0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP.


de Batlle J, Ferrari P, Chajes V, Park JY, Slimani N, McKenzie F, . . . Romieu I. (2015). Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition. Journal of the National Cancer Institute, 107(1), 367. doi:

BACKGROUND: There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC).

METHODS: A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided.

RESULTS: A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P trend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035). CONCLUSIONS: Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

Galeone C, Edefonti V, Parpinel M, Leoncini E, Matsuo K, Talamini R, . . . Boccia S. (2015). Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the international head and neck cancer epidemiology consortium. International Journal of Cancer, 136(4), 904-914. doi:

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR=0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR=0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR=4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Gaspar VM, Costa EC, Queiroz JA, Pichon C, Sousa F, & Correia IJ. (2015). Folate-targeted multifunctional amino acid-chitosan nanoparticles for improved cancer therapy. Pharmaceutical Research, 32(2), 562-577. doi:

PURPOSE: Tumor targeting nanomaterials have potential for improving the efficiency of anti-tumoral therapeutics. However, the evaluation of their biological performance remains highly challenging. In this study we describe the synthesis of multifunctional nanoparticles decorated with folic acid-PEG and dual amino acid-modified chitosan (CM-PFA) complexed with DNA and their evaluation in organotypic 2D co-cultures of cancer-normal cells and also on 3D multicellular tumor spheroids models.

METHODS: The physicochemical characterization of CM-PFA multifunctional carriers was performed by FTIR, (1)H NMR and DLS. 2D co-culture models were established by using a 1:2 cancer-to-normal cell ratio. 3D organotypic tumor spheroids were assembled using micromolding technology for high throughput screening. Nanoparticle efficiency was evaluated by flow cytometry and confocal microscopy.

RESULTS: The CM-PFA nanocarriers (126-176 nm) showed hemocompatibility and were internalized by target cells, achieving a 3.7 fold increase in gene expression. In vivo-mimicking 2D co-cultures confirmed a real affinity towards cancer cells and a negligible uptake in normal cells. The targeted nanoparticles penetrated into 3D spheroids to a higher extent than non-targeted nanocarriers. Also, CM-PFA-mediated delivery of p53 tumor suppressor promoted a decrease in tumor-spheroids volume.

CONCLUSION: These findings corroborate the improved efficiency of this delivery system and demonstrate its potential for application in cancer therapy.

Milne E, Greenop KR, Scott RJ, Haber M, Norris MD, Attia J, . . . Armstrong BK. (2015). Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia. Cancer Epidemiology, Biomarkers & Prevention, 24(1), 48-56. doi:

BACKGROUND: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007).

METHODS: All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed.

RESULTS: There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation.

CONCLUSIONS: Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation.

IMPACT: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger

Multiple vitamins

Jeurnink SM, Ros MM, Leenders M, van Duijnhoven FJ, Siersema PD, Jansen EH, . . . Bueno-de-Mesquita HB. (2015). Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the european prospective investigation into cancer and nutrition: A nested case-control study: Plasma micronutrients and pancreatic cancer risk. International Journal of Cancer, 136(6), E665-76. doi:

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (alpha- and beta-carotene, lycopene, beta-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), alpha- and -tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma beta-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend=0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend=0.06) and alpha-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend=0.08. For alpha- and beta-carotene, lutein, sum of carotenoids and -tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of beta-carotene, zeaxanthin and alpha-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted.


Kodali RT, & Eslick GD. (2015). Meta-analysis: Does garlic intake reduce risk of gastric cancer?. Nutrition & Cancer, 67(1), 1-11. doi:

In the past 2 decades, various epidemiological studies investigated whether garlic can positively modify the risk of gastric cancer. Garlic contains numerous sulfide compounds, including diallyl trisulfide, which have anticarcinogenic properties. We conducted a meta-analysis to determine if garlic intake reduces the risk of gastric cancer. An electronic search of MEDLINE, PubMed, and EMBASE to June 2014 was completed. There were 14 case control studies, 2 randomized controlled studies, and 1 cohort study that fulfilled our inclusion criteria. We used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (CIs) for risk of gastric cancer with garlic consumption. Meta-analysis of a total of 8,621 cases and 14,889 controls was conducted. Significant variability in duration of garlic intake and reference categories for amount of intake was noted. High, low, and any garlic intake were all associated with reduced risk of gastric cancer. High intake had the most significant risk reduction, OR = 0.49 (95% CI: 0.38-0.62). Heterogeneity was low (I(2) = 30.85, P = 0.17). A more modest risk reduction was associated with low intake, OR = 0.75 (95% CI: 0.58-0.97). Half of the studies did not separate garlic intake into high or low amounts, intake was only noted as consumption vs. non-consumption. Any amount of consumption still showed a risk reduction similar to low intake, OR = 0.77 (95% CI: 0.60-1.00). Low and any amount of consumption showed moderate heterogeneity (58% and 45%, respectively). Garlic intake appears to be associated with reduced risk of gastric cancer. Further high quality studies are required to confirm this finding and to assess the amount of garlic that needs to be consumed for protective effect.

Fish/Fish oils

Lovegrove C, Ahmed K, Challacombe B, Khan MS, Popert R, & Dasgupta P. (2015). Systematic review of prostate cancer risk and association with consumption of fish and fish-oils: Analysis of 495,321 participants. International Journal of Clinical Practice, 69(1), 87-105. doi:

INTRODUCTION: Fish-oils have a potential role in inflammation, carcinogenesis inhibition and favourable cancer outcomes. There has been increasing interest in the relationship of diet with cancer incidence and mortality, especially for eicosapantaenoic acid (EPA) and docosahexaenoic acid (DHA). This systematic-analysis of the literature aims to review evidence for the roles of dietary-fish and fish-oil intake in prostate-cancer (PC) risk, aggressiveness and mortality.

METHODS: A systematic-review, following PRISMA guidelines was conducted. PubMed, MEDLINE and Embase were searched to explore PC-risk, aggressiveness and mortality associated with dietary-fish and fish-oil intake. 37 studies were selected.

RESULTS: A total of 495,321 (37-studies) participants were investigated. These revealed various relationships regarding PC-risk (n = 31), aggressiveness (n = 8) and mortality (n = 3). Overall, 10 studies considering PC-risk found significant inverse trends with fish and fish-oil intake. One found a dose-response relationship whereas greater intake of long-chain-polyunsaturated fatty acids increased risk of PC when considering crude odds-ratios [OR: 1.36 (95% CI: 0.99-1.86); p = 0.014]. Three studies addressing aggressiveness identified significant positive relationships with reduced risk of aggressive cancer when considering the greatest intake of total fish [OR 0.56 (95% CI 0.37-0.86)], dark fish and shellfish-meat (p < 0.0001), EPA (p = 0.03) and DHA (p = 0.04). Three studies investigating fish consumption and PC-mortality identified a significantly reduced risk. Multivariate-OR (95% CI) were 0.9 (0.6-1.7), 0.12 (0.05-0.32) and 0.52 (0.30-0.91) at highest fish intakes.

CONCLUSIONS: Fish and fish-oil do not show consistent roles in reducing PC incidence, aggressiveness and mortality. Results suggest that the specific fish type and the fish-oil ratio must be considered. Findings suggest the need for large intervention randomised placebo-controlled trials.


Maccio A, Madeddu C, Gramignano G, Mulas C, Tanca L, Cherchi MC, . . . Ganz T. (2015). The role of inflammation, iron, and nutritional status in cancer-related anemia: Results of a large, prospective, observational study. Haematologica, 100(1), 124-132. doi:

Anemia in oncology patients is often considered a side effect of cancer therapy; however, it may occur before any antineoplastic treatment (cancer-related anemia). This study was aimed to evaluate the prevalence of cancer-related anemia in a large cohort of oncology patients and whether inflammation and malnutrition were predictive of its development and severity. The present study included 888 patients with cancer at different sites between May 2011 and January 2014. Patients were assessed at diagnosis before any cancer treatment. The prevalence of anemia according to the main clinical factors (tumor site, stage and performance status) was analyzed. In each patient markers of inflammation, iron metabolism, malnutrition and oxidative stress as well as the modified Glasgow prognostic score, a combined index of malnutrition and inflammation, were assessed and their role in predicting hemoglobin level was evaluated. The percentage of anemic patients was 63% with the lowest hemoglobin levels being found in the patients with most advanced cancer and compromised performance status. Hemoglobin concentration differed by tumor site and was lowest in patients with ovarian cancer. Hemoglobin concentration was inversely correlated with inflammatory markers, hepcidin, ferritin, erythropoietin and reactive oxygen species, and positively correlated with leptin, albumin, cholesterol and antioxidant enzymes. In multivariate analysis, stage, interleukin-6 and leptin were independent predictors of hemoglobin concentration. Furthermore, hemoglobin was inversely dependent on modified Glasgow Prognostic Score. In conclusion, cancer-related anemia is a multifactorial problem with immune, nutritional and metabolic components that affect its severity. Only a detailed assessment of the pathogenesis of cancer-related anemia may enable clinicians to provide safe and effective individualized treatment.

Allum Vegetables

Turati F, Pelucchi C, Guercio V, La Vecchia C, & Galeone C. (2015). Allium vegetable intake and gastric cancer: A case-control study and meta-analysis. Molecular Nutrition & Food Research, 59(1), 171-179. doi:

SCOPE: To provide new epidemiological data and summarize evidence on the association between allium vegetable intake and gastric cancer risk.

METHODS AND RESULTS: Data were from an Italian case-control study including 230 cases and 547 controls. Odds ratios were derived using multiple logistic regression. We combined results from all published studies using random-effect models. In our case-control study, the odds ratios were 0.59 (95% confidence interval, CI, 0.25-1.41) for >2 portions of onion per week, 0.69 (95% CI, 0.41-1.15) for high garlic intake, and 0.70 (95% CI, 0.39-1.28) for frequent use of both onion and garlic. Besides our study, 22 case-control and four cohort studies were included in the meta-analyses (>10 000 cases). The pooled relative risks for the highest versus lowest intake category were 0.78 (95% CI, 0.67-0.91) for allium vegetables (ten case-control and four cohort studies), 0.60 (95% CI, 0.47-0.76) for garlic (12 case-control studies), and 0.55 (95% CI, 0.41-0.73) for onion (13 case-control studies). The pooled relative risk for high allium vegetable intake from the four cohorts was 1.02 (95% CI, 0.88-1.18).

CONCLUSION: High allium vegetable consumption is likely to reduce gastric cancer risk. This evidence is derived mainly from case-control studies. Further data from large cohorts are desirable for conclusive confirmation.


Rithirangsriroj K, Manchana T, & Akkayagorn L. (2015). Efficacy of acupuncture in prevention of delayed chemotherapy induced nausea and vomiting in gynecologic cancer patients. Gynecologic Oncology, 136(1), 82-86. doi:

OBJECTIVE: To compare the efficacy between acupuncture and ondansetron in the prevention of delayed chemotherapy induced nausea and vomiting (CINV).

METHODS: 70 patients were randomized to receive either 1) acupuncture at P6 point before chemotherapy infusion or 2) ondansetron 8mg intravenously 30min before chemotherapy infusion in their first cycle with cross-over of antiemetic regimen in the consecutive cycle. All patients received dexamethasone 5mg orally twice a day for 3days. Patients were given additional does of ondansetron 4mg orally every 12h if they experienced emesis. Emetic episode, severity of nausea score of 0-10 and adverse events were recorded. Complete response was defined as no nausea, no vomiting and no requirement of additional antiemetic drugs. FACT-G scale was used to evaluate quality of life (QOL) 7days after each cycle of chemotherapy.

RESULTS: The acupuncture group had a significantly higher rate of complete response in the prevention of delayed CINV (52.8% and 35.7%, P=0.02). Compared to another group, the acupuncture group reported significantly lower delayed nausea (45.7% and 65.7%, P=0.004), nausea score (P<0.001) and fewer dosages of additional oral ondansetron (P=0.002). Adverse effects were also significantly lower in the acupuncture group with less frequent constipation (P=0.02) and insomnia (P=0.01). Overall FACT-G scores were significantly higher in the acupuncture group.

CONCLUSION: Acupuncture is effective in preventing delayed CINV and in promoting better QOL. With fewer adverse effects, it may be used as an alternative treatment option for CINV.


Al-Majid S, Wilson LD, Rakovski C, & Coburn JW. (2015). Effects of exercise on biobehavioral outcomes of fatigue during cancer treatment: Results of a feasibility study. Biological Research for Nursing, 17(1), 40-48.doi: 

Cancer treatment is associated with decreased hemoglobin (Hb) concentration and aerobic fitness (VO2 max), which may contribute to cancer-related fatigue (CRF) and decreased quality of life (QoL). Endurance exercise may attenuate CRF and improve QoL, but the mechanisms have not been thoroughly investigated. Objectives. To (a) determine the feasibility of conducting an exercise intervention among women receiving treatment for breast cancer; (b) examine the effects of exercise on Hb and VO2 max and determine their association with changes in CRF and QoL; and (c) investigate changes in selected inflammatory markers. Methods. Fourteen women receiving chemotherapy for Stages I-II breast cancer were randomly assigned to exercise (n = 7) or usual care (n = 7). Women in the exercise group performed supervised, individualized treadmill exercise 2-3 times/week for the duration of chemotherapy (9-12 weeks). Data were collected 4 times over 15-16 weeks. Results. Recruitment rate was 45.7%. Sixteen women consented and 14 completed the trial, for a retention rate of 87.5%. Adherence to exercise protocol was 95-97%, and completion of data collection was 87.5-100%. Exercise was well tolerated. VO2 max was maintained at prechemotherapy levels in exercisers but declined in the usual-care group (p < .05). Hb decreased (p < .001) in all participants as they progressed through chemotherapy. Exercise did not have significant effects on CRF or QoL. Changes in inflammatory markers favored the exercise group. Conclusions. Exercise during chemotherapy may protect against chemotherapy-induced decline in VO2 max but not Hb concentration.

Cormie P, Turner B, Kaczmarek E, Drake D, & Chambers SK. (2015). A qualitative exploration of the experience of men with prostate cancer involved in supervised exercise programs. Oncology Nursing Forum, 42(1), 24-32. doi:

PURPOSE/OBJECTIVES: To provide an in-depth description of the experience of supervised exercise programs among men with prostate cancer and to identify elements critical to optimizing engagement and ongoing exercise participation.

DESIGN: Descriptive, qualitative. SETTING: A tertiary exercise oncology center in Perth, Australia. SAMPLE: 12 men with prostate cancer participating in a structured, clinic-based group exercise program supervised by accredited exercise physiologists.

METHODOLOGIC APPROACH: Participants completed a demographic and health history questionnaire and a semistructured interview. Thematic content analysis was performed.

FINDINGS: Participants described physiological and psychological health benefits, which reduced treatment-related side effects and positively affected self-efficacy, and identified exercise physiologists as providing information about the importance of exercise, as well as practical, emotional, and social support. Peer support encouraged discussion of shared experiences and a sense of social connection.

CONCLUSIONS: Results from the current study expand on existing quantitative data to provide evidence of psychosocial benefits among men with prostate cancer involved with supervised exercise programs. The data provide insight into the components of exercise programs that can form a framework for the development of effective supportive care programs. INTERPRETATION: Involvement in a structured, clinic-based group exercise program provides men with prostate cancer with considerable benefits. Supervision by qualified exercise physiologists and incorporation of a group approach are critical components of maximizing those benefits.


Sprod LK, Fernandez ID, Janelsins MC, Peppone LJ, Atkins JN, Giguere J, . . . Mustian KM. (2015). Effects of yoga on cancer-related fatigue and global side-effect burden in older cancer survivors. Journal of Geriatric Oncology, 6(1), 8-14. doi:

BACKGROUND: Sixty percent of cancer survivors are 65years of age or older. Cancer and its treatments lead to cancer-related fatigue and many other side effects, in turn, creating substantial global side-effect burden (total burden from all side effects) which, ultimately, compromises functional independence and quality of life. Various modes of exercise, such as yoga, reduce cancer-related fatigue and global side-effect burden in younger cancer survivors, but no studies have specifically examined the effects of yoga on older cancer survivors.

OBJECTIVES: The purpose of this study was to assess the effects of a 4-week yoga intervention (Yoga for Cancer Survivors: YOCAS) on overall cancer-related fatigue, and due to its multidimensional nature, the subdomains of cancer-related fatigue (general, physical, emotional, and mental) and global side-effect burden in older cancer survivors.

MATERIALS AND METHODS: We conducted a secondary analysis on data from a multicenter phase III randomized controlled clinical trial with 2 arms (standard care and standard care plus a 4-week YOCAS intervention). The sample for this secondary analysis was 97 older cancer survivors (>60years of age), between 2months and 2years post-treatment, who participated in the original trial.

RESULTS: Participants in the YOCAS intervention arm reported significantly lower cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden than participants in the standard care arm following the 4-week intervention period (p<0.05). CONCLUSIONS: YOCAS is an effective standardized yoga intervention for reducing cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden among older cancer survivors.

Eyles C, Leydon GM, Hoffman CJ, Copson ER, Prescott P, Chorozoglou M, & Lewith G. (2015). Mindfulness for the self-management of fatigue, anxiety, and depression in women with metastatic breast cancer: A mixed methods feasibility study. Integrative Cancer Therapies, 14(1), 42-56. doi:

The impact of living with metastatic breast cancer (MBC) is considerable and psychosocial support can be beneficial. Mindfulness-based stress reduction (MBSR) can help self-management of anxiety, depression, quality of life (QoL), and fatigue and has been evaluated in early-stage breast cancer but not MBC. This study investigated the acceptability and feasibility of providing MBSR for women with MBC and of introducing MBSR into a National Health Service (NHS) setting. A mixed methods convergent design was used. Eligible women with MBC, an Eastern Cooperative Oncology Group (ECOG) score of 0 to 2, stable disease, and life expectancy of at least 6 months were invited to attend (by their oncologist) an 8-week MBSR course. Qualitative interviews with patients, a focus group, and interview with NHS staff were held to explore acceptability and feasibility of MBSR. Questionnaires at baseline, during (weeks 4, 8), and after (weeks 16, 24) the course measured fatigue, anxiety and depression, mindfulness, disease-specific QoL, and generic preference based QoL. Of 100 women approached, 20 joined the study. One woman dropped out prior to the intervention due to illness progression. Nineteen women took part in 3 MBSR courses. Recruitment to 2 of the 3 courses was slow. Commitment to 8 weeks was a reason for non-participation, and proved challenging to participants during the course. Participants found the course acceptable and reported many cumulative and ongoing benefits. These included feeling less reactive to emotional distress and more accepting of the disruption to life that occurs with living with MBC. There was high attendance, completion of course sessions, adherence to home practice, excellent follow-up rates, and high questionnaire return rates. MBSR was acceptable to MBC patients, who perceived benefits such as improved anxiety and QoL; but the MBSR course requires a considerable time commitment. There is scope to tailor the intervention so that it is less intensive.

Fong SS, Ng SS, Lee HW, Pang MY, Luk WS, Chung JW, . . . Masters RS. (2015). The effects of a 6-month tai chi qigong training program on temporomandibular, cervical, and shoulder joint mobility and sleep problems in nasopharyngeal cancer survivors. Integrative Cancer Therapies, 14(1), 16-25. doi:

Introduction. Nasopharyngeal cancer (NPC) survivors often sustain head-neck-shoulder impairments from conventional treatments, which could disturb sleep. This novel study aimed to examine the efficacy of Tai Chi (TC) Qigong in optimizing temporomandibular joint (TMJ), cervical, and shoulder joint mobility and reducing sleep problems in NPC survivors. Methods. Fifty-two NPC survivors participated in the study. The experimental group (n = 25) received 6 months of TC Qigong training (1.5 h/session; 4 sessions/wk including self-practice) while the control group (n = 27) received no training. Cervical side flexion and rotation, shoulder flexion and horizontal flexion range of motion (ROM), mouth opening capacity (interincisor distance), and sleep problems (Medical Outcomes Study Sleep Scale) were assessed at baseline, mid-intervention (3 months), immediately after TC Qigong training, and at 6-month follow-up. Results. Intention-to-treat analysis revealed improvement in cervical side flexion ROM only (P .008) after the TC Qigong training. Deterioration was observed in shoulder flexion ROM and mouth opening capacity in the no-training controls over time (P < .008). Sleep problems also decreased in the TC Qigong group (P < .008), and this effect was most profound during the follow-up period. In addition, improvement in cervical side flexion ROM was associated with a reduction in sleep problems in the experimental group after TC Qigong training (P < .05). Conclusions. The 6-month TC Qigong intervention improved neck mobility, maintained TMJ and shoulder joint mobility, and reduced sleep problems for NPC survivors. TC Qigong could be an effective nonpharmacological intervention for managing progressive trismus, chronic neck and shoulder hypomobility, and reducing sleep problems among NPC survivors.

Keshet Y, Schiff E, Samuels N, & Ben-Arye E. (2015). Giving voice to cancer patients: Assessing non-specific effects of an integrative oncology therapeutic program via short patient narratives. Psycho-Oncology, 24(2), 169-174. doi:

OBJECTIVE: The aim of this study was to assess patient perspectives regarding non-specific effects of a complementary medicine (CM) consultation and intervention within an integrative oncology setting.

METHODS: Patients undergoing chemotherapy in a community-based oncology service were referred by oncology healthcare providers to an integrative oncology physician trained in CM-oriented supportive care. Assessment of concerns and well-being was made using the Measure Yourself Concerns and Wellbeing questionnaire, at baseline and after 3 months of CM treatments, which were designed to improve quality of life (QoL) outcomes. Patients were asked to describe the most important aspects of the integrative treatment process. Free-text narratives were examined using content analysis with ATLAS.Ti software for systematic coding.

RESULTS: Of 152 patients' narratives analyzed, 44% reported an experience of patient-centered care, including CM practitioners' approach of togetherness, uniqueness, and the invoking of an internal process. CM practitioner approach was experienced within a context of an enhanced sense of confidence; gaining a different perspective; and acquiring emotional resilience and empowerment.

CONCLUSIONS: Short patient narratives should be considered for patient-reported outcomes, expressing perspectives of both effects and experience of care. CM may promote patient QoL-related outcomes through non-specific effects, enhancing patient-centered care. The benefits of CM dependent on general therapeutic incidental aspects (i.e., common factors) warrant attention regarding non-specific components of treatment.

Labelle LE, Campbell TS, Faris P, & Carlson LE. (2015). Mediators of mindfulness-based stress reduction (MBSR): Assessing the timing and sequence of change in cancer patients. Journal of Clinical Psychology, 71(1), 21-40. doi:

OBJECTIVES: This waitlist-controlled study examined the timing of changes during Mindfulness-Based Cancer Recovery (MBCR), and explored sequential mediated effects through enhanced mindfulness and emotion regulation (ER) in a cancer population.

METHOD: Patients were recruited from the MBCR program waitlist and were either registered for immediate participation (n = 135) or waiting for the next program to begin (n = 76). Participants completed self-report measures of stress symptoms, mood disturbance, mindfulness, and ER (rumination, worry, and experiential avoidance) pre-, mid- and post-MBCR or waiting period.

RESULTS: There was a relatively early effect of MBCR on observing, nonjudging, rumination, and worry. All other measures changed later. Early changes in present-focused nonjudgmental awareness, rumination, and worry mediated the effect of MBCR on mindfulness skills such as nonreactivity later on.

CONCLUSION: The constructs of mindfulness and ER may overlap and changes may be mutually facilitative during MBCR. The study informs our understanding of mindfulness and ER as mechanisms of mindfulness-based interventions.