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Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.
Chávez-Hidalgo, LP, Martín-Fernández-de-Labastida, S, M de Pancorbo, M, Arroyo-Izaga, M
World journal of gastroenterology. 2023;29(7):1219-1234
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Colorectal cancer (CRC) is the third most frequent type of cancer and yet has the second highest mortality rate in cancer patients worldwide. Hence there is an urgency to understand more about dietary and lifestyle factors that can help to prevent this type of cancer. It is known that folate has a preventive function in CRC, possibly due to its role in DNA methylation. Methylation is the addition of methyl groups to DNA, which influences gene expression and regulation. This systematic review investigated how folate and other dietary methyl groups and methyl influencers such as B vitamins and alcohol influence the development of CRC, whilst also considering various genetic variants in methyl-metabolising enzymes (polymorphisms). The analysis included a total of 19 case-control and cohort studies and highlighted that potential interactions between methyl donor nutrients, genetic variants, and alcohol influence CRC risk. For most, high levels of folate intake were considered a protective factor, while high alcohol consumption proved to be a risk factor. Yet these interactions appear to be complex, with gender, genetic variations and folate status appearing to contribute to variable and, in some cases, contradictory outcomes. The authors suggested in their findings that Vitamin B6, Vitamin B3 (Niacin), and alcohol may affect CRC by influencing its risk by acting on both the genetic code itself and the epigenetic factors that control gene activity. Further research is needed to better understand the complexity of these mechanisms, and to help clarify the influence of methyl group donors as epigenetic regulators of gene activity in CRC development.
Abstract
BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
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Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis.
Vichos, T, Rezaie, A, Vichos, P, Cash, B, Pimentel, M
Digestive diseases and sciences. 2023;68(6):2585-2596
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Colorectal cancer (CRC) is one of the most common cancers and adenomatous colorectal polyps (CRP) are a risk factor for developing CRC. The potential role of functional disturbances seen in irritable bowel syndrome (IBS) for the development of CRC are not yet clear. The aim of this systematic review and meta-analysis was to evaluate the occurrence of CRC and CRP in IBS patients. 14 cohort studies with a total of 654,764 IBS patients and 2,277,195 controls and six cross-sectional studies with 26,641 IBS patients and 87,803 controls were included in the review. Based on the pooled data from 5 cross-sectional studies, IBS patients had a significantly lower occurrence of CRP (by 71%). CRC risk was also reduced but this did not reach statistical significance. Only four of the 14 cohort studies were included in the meta-analysis and, again, CRC risk was lower in IBS patients but this was not statistically significant.
Abstract
OBJECTIVES Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. METHODS Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. RESULTS Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). CONCLUSION Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.
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Mycotoxin-Linked Mutations and Cancer Risk: A Global Health Issue.
Ekwomadu, T, Mwanza, M, Musekiwa, A
International journal of environmental research and public health. 2022;19(13)
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Mycotoxins are toxic substances produced by fungi, which can be found in common foods like maize, wheat, nuts, and foods containing them. Mycotoxins such as aflatoxins, ochratoxin, fumonisins, zearalenone, and some Penicillium toxins can alter genetic material. According to previous studies, they can damage genetic material and affect cell growth. Usage of chemicals such as fertilizers and fungicides is a common practice in the agricultural industry to protect plants from fungus and to feed them. However, fungicides can accelerate mycotoxin production. 16 studies were included in this Systematic Review and 11 in Meta-Analysis. This research looked at the harmful effects of mycotoxins such as aflatoxins, fumonisins, ochratoxin, T2, zearalenone, and some Penicillium toxins in causing cancers. The researchers evaluated the link between aflatoxin exposure and liver cancer, fumonisin B1 exposure and liver cancer, zearalenone exposure and breast cancer, zearalenone exposure and cervical cancer, citrinine and patulin exposure and colorectal cancer, and NEO, HT-2, and T-2 exposure and Oesophageal cancer. This research did not show significant associations between various mycotoxins and cancer risk. As currently, most studies are primarily focused on aflatoxin; more robust studies are needed to assess the cancer risk associated with different mycotoxin exposure. Using the results of this study, healthcare professionals can gain a better understanding of how mycotoxins affect our bodies.
Abstract
Humans continue to be constantly exposed to mycotoxins, mainly through oral exposure (dietary), inhalation, or dermal contact. Recently, it has been of increasing interest to investigate mycotoxin-linked carcinogenicity. This systematic review was conducted to synthesize evidence of the association between mycotoxin-linked mutations and the risk of cancer, to provide an overview of the data linking exposure to different mycotoxins with human cancer risk, and to provide an update on current research on the risk of cancer associated with human exposure to mycotoxins. PRISMA guidelines were used when conducting the systematic review. PubMed, MEDLINE, and CINAHL electronic databases were comprehensively searched to extract the relevant studies published from inception to May 2022. A total of sixteen relevant studies (4907 participants) were identified and included in this review. Of these, twelve studies were from Asia, while four of the studies were conducted in Africa. The overall meta-analysis result found no significant association, although some of the studies confirmed an association between mycotoxin-linked mutations and primary liver cancer risk. Mainly, the experimental studies have shown associations between mycotoxin-linked mutations and cancer risk, and there is a need for researchers to confirm these links in epidemiological studies in order to guide public health policies and interventions.
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Egg and Dietary Cholesterol Intake and Risk of All-Cause, Cardiovascular, and Cancer Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.
Darooghegi Mofrad, M, Naghshi, S, Lotfi, K, Beyene, J, Hypponen, E, Pirouzi, A, Sadeghi, O
Frontiers in nutrition. 2022;9:878979
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Eggs are a rich source of vitamins, carotenoids, and dietary cholesterol. However, dietary cholesterol may contribute to an imbalance in blood lipid levels, increasing the risk of developing cardiovascular disease (CVD) and cancer. Therefore, this systematic review and dose-response meta-analysis evaluated the impact of egg and dietary cholesterol on the risk of CVD, cancer, and all-cause mortality. This systematic review and meta-analysis included fifty-five prospective cohort studies. This research showed a positive association between egg and dietary cholesterol consumption with all-cause mortality and cancer mortality. However, daily consumption of up to 1.5 eggs or 450 mg of dietary cholesterol did not affect the mortality risk. Further robust studies are required due to the high heterogeneity between the included studies. Nevertheless, healthcare professionals can use the results of this research to understand the impact of egg and dietary cholesterol consumption on CVD, cancer and all-cause mortality.
Abstract
OBJECTIVE This systematic review and meta-analysis of prospective cohort studies examined the associations between egg and dietary cholesterol intake and the risk of mortality from all causes, including cardiovascular disease (CVD) and cancer. METHODS We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until April 2021, as well as references to the relevant articles retrieved. Random-effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CIs) for the highest vs. lowest categories of egg and dietary cholesterol intake. Also, linear and non-linear dose-response analyses were conducted to examine the dose-response relationships. RESULTS We included 55 studies, comprising data from 2,772,486 individuals with 228,425, 71,745, and 67,211 cases of all-cause, CVD, and cancer mortality, respectively. Intake of each additional egg per day was associated with a 7% higher risk of all-cause (1.07, 95% CI: 1.02-1.12, I2 = 84.8%) and a 13% higher risk of cancer mortality (1.13, 95% CI: 1.06-1.20, I2 = 54.2%), but was not associated with CVD mortality (1.00, 95% CI: 0.92-1.09, I2 = 81.5%). Non-linear analyses showed increased risks for egg consumption of more than 1.5 and 0.5 eggs/day, respectively. Each 100 mg/day increment in dietary cholesterol intake was associated with a 6% higher risk of all-cause mortality (1.06, 95% CI: 1.03-1.08, I2 = 34.5%) and a 6% higher risk of cancer mortality (1.06, 95% CI: 1.05-1.07, I2 = 0%), but was not associated with CVD mortality (1.04, 95% CI: 0.99-1.10, I2 = 85.9%). Non-linear analyses demonstrated elevated risks of CVD and cancer mortality for intakes more than 450 and 250 mg/day, respectively. CONCLUSIONS AND RELEVANCE High-dietary intake of eggs and cholesterol was associated with all-cause and cancer mortality. Little evidence for elevated risks was seen for intakes below 0.5 egg/day or 250 mg/day of dietary cholesterol. Our findings should be considered with caution because of small risk estimates and moderate between-study heterogeneity. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=252564, PROSPERO, identifier: CRD42021252564.
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Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis.
Sari Motlagh, R, Abufaraj, M, Karakiewicz, PI, Rajwa, P, Mori, K, Mun, DH, Shariat, SF
World journal of urology. 2022;40(4):907-914
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The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is equal in both sexes; however, disease severity and progression rates are approximately three times higher in the male gender. Androgen deprivation therapy (ADT) and the second-generation androgen receptor targeting therapy were developed to suppress the androgen-activated intracellular cascade that leads to tumour progression and aggressive tumour growth. The aim of this study was to assess the risk of SARS-CoV-2 infection and the severity of disease in prostate cancer (PCa) patients treated with ADT. This study is a systematic review and meta-analysis of six cohort studies. The study results show that there is not a significant association between ADT use and the severity of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) in PCa patients. However, results also show that ADT does not worsen COVID-19 risk and trajectory. Authors conclude that ADT, as a cancer treatment, might be safely administered to patients during the COVID-19 pandemic.
Abstract
PURPOSE Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). METHODS We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I2 statistic, respectively. RESULTS Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68). CONCLUSION We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.
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Association of Retinol and Carotenoids Content in Diet and Serum With Risk for Colorectal Cancer: A Meta-Analysis.
Han, X, Zhao, R, Zhang, G, Jiao, Y, Wang, Y, Wang, D, Cai, H
Frontiers in nutrition. 2022;9:918777
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The incident rate of malignant tumours has been increasing, and so has colo-rectal cancer (CRC), which is now the third most frequent cancer and the second most common cause of cancer death. CRC development is influenced by environmental and genetic factors. Diet, diabetes, obesity, lack of physical activity, age, family history and history of benign adenomatous polyps and inflammatory bowel disease are all known risk factors. Modulating diet is one way to modify cancer risk. Vitamin A (retinol) and carotenoids, which are precursors to Vitamin A, are indispensable in the human body and widely occur in a range of vegetables, fruits and animal-derived foods. In some studies high dietary intake of retinol and carotenoids had been linked to a decreased risk of CRC, however, this was not consistent in all findings. To get a better understanding of this matter, the authors of this meta-analysis analysed 22 clinical studies from the last 20 years. The authors found an inverse association with carotenoids in blood serum, so higher blood serum of carotenoids seemed to decrease CRC risk. In regards to dietary intake, total carotenoid intake did not increase CRC risk and in fact the carotenoids carotenes, lycopene, and β-cryptoxanthin reduced risk, which was particularly noticeable in men. In women, high dietary intake of retinol also showed to reduce CRC risk, but it appeared to increase the risk in men. This raised the idea of gender-specific differences. Of clinical relevance are that carotenoids can be an important dietary contributors in reducing CRC risk. However the protective role of retinol appears to be gender-specific and only seems to benefit women, with the opposite effect in men.
Expert Review
Conflicts of interest:
None
Take Home Message:
The results of this study were mixed:
- Total dietary intake of carotenoids was not associated with CRC risk.
- Case control studies found that high serum carotenoids may increase CRC risk.
- There were differences in findings between males and females.
- Larger, well-controlled studies over long time frames are needed to further explore the relationship between dietary intake and serum concentrations of carotenoids and retinol with CRC. These studies should include results by sex, race and dose response.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Colorectal cancer (CRC) is the third most common cancer worldwide, and second in terms of mortality. Diet and environmental factors may have a strong influence and causative effect. Research has linked dietary consumption and serum levels of carotenoids and retinol with CRC. However, results have been mixed.
The aim of this meta analysis was to identify a potential association between CRC and carotenoid and retinol intake. A total of 22 cohort and case control studies published between 2000-2019 from across Europe, North America and Asia were included. The number of CRC cases totalled 19,293 from a sample of more than 450,000 people.
Eligible studies reported data in either relative risk (RR) or odds ratios (OR) with 95% confidence intervals (95% CI). In the meta analysis, data were combined and expressed as OR with 95% CI.
Cases and control groups were based on high or low carotenoid intake as defined by the included studies and based on dietary intake or serum concentration. Sub-group analysis was undertaken by study type, sex and tumour type. A sensitivity analysis tested the robustness of the results.
Due to the heterogeneity between studies, adjustments were made for potential covariates and confounding factors including age, gender, a family history of CRC, smoking, alcohol consumption and levels of physical activity.
The quality of the studies was assessed against predefined inclusion and exclusion criteria and scored using the Newcastle-Ottawa Scale (NOS).
The nutrients studied included; beta-carotene, alpha-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin and retinol. These were assessed through dietary intake or serum concentrations.
Key Findings
- High dietary intake of beta-carotene was not associated with an increased risk of CRC in females (OR = 0.97; 95%CI 0.79-1.19), however, it may lower CRC risk in males (OR = 0.74; 95% CI 0.55-0.99).
- High dietary intake of retinol was not associated with CRC risk (OR = 0.99; 95% CI 0.89-1.10). However, the findings suggested that it may reduce CRC risk in females but increase CRC risk in males.
- There was a tendency towards a slightly decreased risk of CRC with high dietary intakes of alpha-carotene), lycopene, and beta-cryptoxanthin. The results were more pronounced in males.
- No association was found between high consumption of high lutein/zeaxanthin, retinol or total carotenoids and the risk of CRC
- Case control studies found a negative association between serum carotenoids and CRC risk. This relationship was not found in cohort studies and therefore remains uncertain.
Conclusions
This was a well-conducted meta-analysis that was not subject to any conflicts of interest. Larger, well controlled prospective studies adjusting for sex and with long-term follow-up are needed to confirm the relationship between dietary intake and serum levels of carotenoids and CRC.
Notes: The authors had no conflicts of interest to disclose.
Clinical practice applications:
- Healthcare practitioners working with people with a family history of CRC or those who may be at increased risk may like to consider increasing carotenoid intake modestly.
- A modest increase in dietary intake of beta-carotene for males may be beneficial.
- A modest increase in dietary retinol may be beneficial for females.
Considerations for future research:
- Further research is needed to explore the differences between sexes for dietary intake of carotenoids and retinol and CRC risk
- Further studies are needed to investigate the relationship between serum carotenoids and CRC
- Analysis of results by race and continent may be beneficial
- Further research is needed to define dose response
- Due to heterogeneity between studies, large, well controlled studies over long time frames are needed
Abstract
Background: Colorectal cancer (CRC) risk is linked to serum and dietary retinol and carotenoids, according to clinical and epidemiological research. However, the findings are not consistent. As a result, we did this meta-analysis to determine the link between them. Methods: From 2000 through 2022, the PubMed, Web of Science, and Embase databases, as well as pertinent article references, were searched and filtered based on inclusion and exclusion criteria and literature quality ratings. High and low intake were used as controls, and OR (odds ratio) or RR (relative risk) and 95% confidence interval were extracted. The extracted data were plotted and analyzed using Stata12.0 software. Results: A total of 22 relevant studies were included, including 18 studies related to diet and 4 studies related to serum. For high and low intake or concentration controls, the pooled OR was as follows: β-carotene (OR = 0.89, 95% CI: 0.78-1.03), α-carotene (OR = 0.87, 95% CI: 0.72-1.03), lycopene (OR = 0.93, 95% CI: 0.81-1.07), lutein/zeaxanthin (OR = 0.96, 95% CI: 0.87-1.07), β-cryptoxanthin (OR = 0.70, 95% CI: 0.48-1.01), total carotenoids (OR = 0.97, 95% CI: 0.81-1.15), retinol (OR = 0.99, 95% CI: 0.89-1.10), serum carotenoids (OR = 0.73, 95% CI: 0.58-0.93), serum retinol (OR = 0.62, 95% CI: 0.26-1.49). Subgroup analysis was performed according to tumor type, study type and sex. Conclusion: Total carotenoid intake and Lutein/Zeaxanthin intake were not associated with CRC risk. High β-carotene, α-carotene, lycopene, and β-cryptoxanthin all tended to reduce CRC risk. Serum carotenoid concentrations were significantly inversely associated with CRC risk.
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The Dose-Response Associations of Sugar-Sweetened Beverage Intake with the Risk of Stroke, Depression, Cancer, and Cause-Specific Mortality: A Systematic Review and Meta-Analysis of Prospective Studies.
Wang, Y, Zhao, R, Wang, B, Zhao, C, Zhu, B, Tian, X
Nutrients. 2022;14(4)
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The consumption of sugar-sweetened beverages is high in today's society, which may lead to weight gain, inflammation, and a number of obesity-associated diseases. The objective of this systematic review and meta-analysis was to investigate the associations and causal links between the consumption of sugar-sweetened beverages and cancer, stroke, depression, and cause-specific mortality. Consumption of sugar-sweetened beverages significantly increased the risk of cancer, strokes, depression, and cause-specific mortality when compared with the consumption of low or no-sugar-sweetened beverages. As little as a 250ml increment of sugar-sweetened beverages was associated with an increase in risk. Consumption of sugar-sweetened beverages increases the risk of ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% compared to those who consume less or no sugar-sweetened beverages. These findings can be used by healthcare professionals to understand the clinical significance of intervention strategies that reduce the consumption of sugar-sweetened beverages. It is imperative to conduct additional robust studies as there is an insufficient amount of evidence at present to establish a causal connection between the consumption of sugary beverages and the risk of depression, stroke, cancer, and cause-specific mortality.
Abstract
The associations between sugar-sweetened beverage (SSB) consumption and the risk of stroke, depression, cancer, and cause-specific mortality have not been determined, and the quantitative aspects of this link remain unclear. This meta-analysis therefore conducted a systematic review and dose-response analysis to determine their causal links. The database searches were conducted in PubMed, Cochrane library, Embase, Web of Science up to 10 November 2021. The intervention effects were evaluated by relative risk (RR) with 95% confidences (CI). Thirty-two articles met the inclusion criteria. Higher levels of SSB consumption significantly increased the risk of stroke (RR 1.12, 95% CI 1.03-1.23), depression (1.25, 1.11-1.41), cancer (1.10, 1.03-1.17), and all-cause mortality (1.08, 1.05-1.11) compared with none or lower SSB intake. The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 (1.03-1.15), 1.08 (1.06-1.10), 1.17 (1.04-1.32), and 1.07 (1.03-1.11), respectively. The link was curved for depression and cancer risk (pnon-linear < 0.05). Subgroup analysis suggested that higher SSB intake increased ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% than none or lower SSB consumption. It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).
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8.
Lipid Intake and Breast Cancer Risk: Is There a Link? A New Focus and Meta-Analysis.
Lodi, M, Kiehl, A, Qu, FL, Gabriele, V, Tomasetto, C, Mathelin, C
European journal of breast health. 2022;18(2):108-126
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Incidence of breast cancer is the leading cause of cancer-related mortality, accounting for 15.5% of all cancer-related deaths. However, there is a lack of complete understanding of the effects of different types of dietary lipids on breast cancer development, such as saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), dietary cholesterol, polyunsaturated fatty acids (PUFA), and unsaturated trans fatty acids (TFA). An evaluation of the effect of lipid consumption on breast cancer and the impact it has on menopausal status was conducted in this meta-analysis, which included forty-four studies. Increased saturated fatty acid intake was associated with an increased risk of breast cancer in postmenopausal women. However, breast cancer risk was not associated with increased consumption of total fat, SFA, MUFA, PUFA, and cholesterol in premenopausal women. The effects of estrogen and the release of proinflammatory cytokines by adipocytes should be evaluated, as well as other pathways that contribute to the development of breast cancer. There is a need for further robust studies to evaluate the effects of different types of lipid consumption on breast cancer. Although the association between SFA and breast cancer is weak, healthcare professionals can use this study's findings to better understand the detrimental effect of SFA, despite the fact that there is a great deal of heterogeneity in the current analysis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The authors found no association between total fat, saturated fatty-acids, mono and poly-unsaturated fatty acids and cholesterol intake and breast cancer incidence in the general population and in pre-menopausal women.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- Among lifestyle-related breast cancer risk factors, the role of diet in breast cancer remains uncertain.
- The authors highlight a weak association between high SFA consumption and breast cancer risk in post-menopausal women.
- The authors found no association between total fat, saturated fatty-acids, mono and poly-unsaturated fatty acids and cholesterol intake and breast cancer incidence in the general population and in pre-menopausal women.
Objectives
- To determine if there is an association between total lipid intake, saturated fatty acid (SFA), Poly- and Mono-Unsaturated Fatty Acid (PUFA and MUFA) and cholesterol intake and breast cancer risk.
Results
- Forty-four articles were included in the meta-analysis, consisting of 28 case-control studies and 16 cohort studies.
- In total, this meta-analysis involved 1,185,896 women, of whom 54,553 had breast cancer.
- There was no association between total fat, SFA, MUFA, PUFA and cholesterol intake and breast cancer in the general population and in pre-menopausal women.
- In postmenopausal women, high SFA consumption was associated with increased breast cancer risk in case-control studies [relative risk (RR): 1.12; confidence interval (CI) 95%: 1.03–1.21; p = 0.006 but not in cohort studies (RR: 1.01; CI 95%: 0.85–1.19; p = 0.93).
Limitations
- Studies included in the meta-analysis were carried out on populations from five continents with significant cultural and dietary diversity, and well as different types of oils used in the diet
Conclusion
- At this stage, the authors state it is not possible to establish nutritional recommendations regarding the consumption of lipids to decrease breast cancer risk.
Clinical practice applications:
- The results of this meta-analysis does not demonstrate a statistically significant link between high consumption of total lipids, PUFA, MUFA and cholesterol and the occurrence of breast cancer.
- However, the results suggest that there is an association between SFA intake and breast cancer risk in postmenopausal women, although this was only found in case-controlled studies and not cohort studies.
- While obesity is a known breast cancer risk factor after menopause, the link between the effect of diet and the effect of obesity on the breast may be through different mechanisms.
- The authors investigated if high lipid consumption acts on breast tissue by the same mechanisms as obesity, and found the association between SFA intake and breast cancer risk in postmenopausal women must be through other biological explanations.
- The authors found that while high SFA consumption may increase breast cancer risk among post-menopausal women, biological mechanisms linking SFA and breast cancerogenesis are still unknown.
- The meta-analysis found high blood cholesterol levels appear to increase the risk of breast cancer. However, the authors could not confirm that high dietary cholesterol intake is a risk factor for breast cancer. The authors postulated this may be in part due to the low proportion of cholesterol (about 30%) in the diet, while the rest comes from the degradation of lipids and carbohydrates by the liver.
Considerations for future research:
- As lipids can have different actions in the same family, studies should rather focus on specific lipid consumption
Abstract
Objective: To determine if there is an association between total lipid intake, saturated fatty acid (SFA), Poly- and Mono-Unsaturated Fatty Acid (PUFA and MUFA) and cholesterol intake and breast cancer risk. Materials and Methods: We conducted a systematic review of the literature and a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all cohort and case-control studies published up to December 2020 with subgroup analysis according to menopausal status. Results: We included 44 articles for analysis. There was no association between total fat, SFA, MUFA, PUFA and cholesterol intake and breast cancer in the general population and in pre-menopausal women. In postmenopausal women, high SFA consumption was associated with increased breast cancer risk in case-control studies [relative risk (RR): 1.12; confidence interval (CI) 95%: 1.03-1.21; p = 0.006 but not in cohort studies (RR: 1.01; CI 95%: 0.85-1.19; p = 0.93). Conclusion: There was a weak association between high SFA consumption and breast cancer risk in post-menopausal women, however there was high heterogeneity for this analysis. As lipids can have different actions in the same family, studies should rather focus on specific lipid consumption.
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Association between dietary inflammatory index and oral cancer risk: A systematic review and dose-response meta-analysis.
Luo, Z, Zhu, X, Hu, Y, Yan, S, Chen, L
Frontiers in oncology. 2022;12:920452
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Oral cancer is the most prevalent subtype of head and neck cancers. Inflammation and oxidative stress triggered by certain dietary components may be a potential mechanism for oral cancer. The aim of this study was to comprehensively assess the dose–response relationship between dietary inflammatory index (DII) and oral cancer risk. This study is a systematic review and meta-analysis of five studies. The studies were all case–control studies with a total of 1,278 cases and 5,137 controls. Results show that a more pro-inflammatory diet, represented by the higher DII score, was associated with an elevated risk of oral cancer. Authors conclude that reducing pro-inflammatory food components and promoting anti-inflammatory food components would be beneficial in the prevention and control of oral cancer.
Abstract
Background: Dietary inflammatory index (DII) has been suggested to be associated with oral cancer risk. However, a quantitative comprehensive assessment of the dose-response relationship has not been reported. We performed a meta-analysis to clarify the risk of oral cancer with DII. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to 1 March 2022. Fixed- or random-effects models were utilized to estimate the pooled odds ratio (OR) of oral cancer with DII, as appropriate. Restricted cubic splines were used to model the dose-response relationship. Results: We included five case-control studies involving 1,278 cases and 5,137 controls in the meta-analysis. Risk of oral cancer was increased by 135% with the highest versus lowest DII level [OR: 2.35, 95% confidence interval (CI): 1.88-2.94], and 79% with higher versus lower DII level (OR: 1.79, 95% CI: 1.49-2.15). We found no evidence of a nonlinear dose-response association of DII with oral cancer (pnon-linearity = 0.752), and the risk was increased by 17% (OR: 1.17, 95% CI: 1.05-1.30) with 1 unit increment in DII score. Conclusion: This meta-analysis suggested that a higher DII score was associated with increased risk of oral cancer. Therefore, reducing pro-inflammatory components and promoting anti-inflammatory components of diet may be effective in the prevention of oral cancer.
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Disturbances of Vaginal Microbiome Composition in Human Papillomavirus Infection and Cervical Carcinogenesis: A Qualitative Systematic Review.
Wu, M, Li, H, Yu, H, Yan, Y, Wang, C, Teng, F, Fan, A, Xue, F
Frontiers in oncology. 2022;12:941741
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Cervical cancer remains the fourth most prevalent cancer in women worldwide. The infection of certain strains of human papillomavirus (HPV)) are thought to have an important causative role in the development of cervical cancer. But since a vast majority of HPV infections clear naturally within a few months, this indicates other factors at play determine the progression of the disease and its cancerous developments. Recent findings indicate that there may be a close link between disruptions of the vaginal microbiome and HPV infection, cervical lesions, cervical cancer and other gynaecological diseases. However, the evidence thus far is quite varied. Hence this systematic review sought to gather the current evidence and integrate it to create up-to-date knowledge. Included were the 22 studies relating to vaginal microbiota, and women with HPV-associated cervical diseases. The studies were conducted in various countries around the world and contained a mixture of case-controlled, cross-sectional and longitudinal studies. The authors acknowledge the challenges of summarising the findings due to differences in how the studies have been conducted. The results of the review showed that vaginal disturbances in HPV infections and related cervical diseases, seem to manifest in decreases in Lactobacilli, and increases in aerobic and anaerobic bacteria. Lactobacillus iners seemed to have either protective or pathogenic effects. They also noted that there are geographical and ethnic differences and patterns, which made the consolidation of results more challenging. For future research, the authors deemed the role of the Lactobacillus family of particular interest.
Abstract
BACKGROUND Emerging evidence has demonstrated a close association between perturbations in vaginal microbiota composition in women and human papillomavirus (HPV) infection, cervical lesions, and cervical cancer (Ca); however, these findings are highly heterogeneous and inconclusive. AIM: To perform a comprehensive systematic review of the global disturbance in the vaginal microbiota, specifically in women with HPV-associated cervical diseases, and to further conduct within- and across-disease comparisons. METHOD Twenty-two records were identified in a systematic literature search of PubMed, Web of Science, and Embase up to February 28, 2022. We extracted microbial changes at the community (alpha and beta diversity) and taxonomic (relative abundance) levels. Within- and across-disease findings on the relative abundance of taxonomic assignments were qualitatively synthesized. RESULTS Generally, significantly higher alpha diversity was observed for HPV infection, cervical lesions, and/or cancer patients than in controls, and significant differences within beta diversity were observed for the overall microbial composition across samples. In within-disease comparisons, the genera Gardnerella, Megasphaera, Prevotella, Peptostreptococcus, and Streptococcus showed the greatest abundances with HPV infection; Sneathia and Atopobium showed inconsistent abundance with HPV infection, and Staphylococcus was observed in Ca. Across diseases, we find increased levels of Streptococcus and varying levels of Gardnerella were shared across HPV infections, high-grade squamous intraepithelial lesions, and Ca, whereas Lactobacillus iners varied depending on the HPV-related disease subtype. CONCLUSIONS This systematic review reports that vaginal microbiome disturbances are correlated to the depletion of Lactobacillus, enrichment of anaerobes, and increased abundance of aerobic bacteria in HPV infection and related cervical diseases. Moreover, L. iners may exert either protective or pathogenic effects on different HPV-related diseases.