Does sugar cause cancer? Specifically, what role does glycosylation - - PowerPoint PPT Presentation

Does sugar cause cancer?

Specifically, what role does glycosylation play in oncogenesis?

Allison Hayward and Sarah Lopes

First of all...

These two questions are actually different topics, and there are no available studies that address both. Glycosylation is the addition of a glycan (carbohydrate) to a protein, for structural or functional purposes. Aberrant (abnormal) glycosylation is a “hallmark” of cancer. Studies on this topic are very technical, examining changes to DNA that occur during cancer development. Glycosylation is not a direct response to dietary sugar intake, and abnormal glycosylation is a feature of cancer cells, not a cause of cancer development.

• 1. Sugars in diet and risk of cancer in the NIH-AARP Diet

and Health Study

Tasevska N, Jiao L, Cross AJ, et al. (2012) Overview and Methods:

AARP members were recruited from 8 U.S. states with the use of a questionnaire send by mail. At baseline, subjects completed a FFQ measuring intake of 124 food items over the previous 12 months. Multiple exclusion criteria reduced a potential population of 617,119 respondents to n = 435,674. Associations between sugar intake and 24 malignancies were investigated in this population of adults, aged 50-71 years. Over the course of 7.2 years, cancer was diagnosed in 29,099 men and 13,355 women.

• 1. Sugars in diet and risk of cancer in the NIH-AARP Diet

and Health Study

Tasevska N, Jiao L, Cross AJ, et al. (2012) Overview and Methods:

Sugar consumption was measured in several subcategories: total sugars, sucrose, fructose, added sugars, added sucrose, and added fructose. Consumption of each subcategory of sugars was broken into quintiles for comparative analysis. Both separate and combined gender analyses were performed. The authors discuss hypotheses suggesting that high-sugar diets may play a role in cancer development due to their stimulation of insulin and insulin-like growth factor-I (IGF-I) synthesis and well as promoting oxidative stress and that added sugars affect the body differently than integral sugars due to the fact that they are “free in solution” and thus rapidly metabolized.

• 1. Sugars in diet and risk of cancer in the NIH-AARP Diet

and Health Study

Tasevska N, Jiao L, Cross AJ, et al. (2012) Results: Positive Correlations:

• A strong positive association was found between intake of added sugars and risk for esophageal

adenocarcinoma in gender-combined analysis.

• All investigated sugars were related to increased risk of pleural (between the lung and chest cavity) cancer.
• In women, total sugars, added sugars and added fructose intakes were positively associated with risk of

leukemia, and high fructose intake was associated with increased risk of bladder cancer.

• High intake of fructose, and added fructose in particular, was correlated with a greater than two-fold

increase in risk for small intestine cancer.

• Positive correlations found for rarer cancers, and inconsistency in results between genders suggest a

possibility for some chance results.

• 1. Sugars in diet and risk of cancer in the NIH-AARP Diet

and Health Study

Tasevska N, Jiao L, Cross AJ, et al. (2012) Results: Inverse Correlations or No Association:

None of the investigated sugars were associated with increased risk of potentially IGF-I-related cancers such as colorectal, breast, prostate, pancreatic or endometrial cancer. Total sugars, fructose, and added fructose intake were associated with decreased risk of all cancers in men. In women, all investigated sugars were inversely associated with risk of ovarian cancer and added sucrose and added fructose were inversely associated with pancreatic cancer. High added fructose intake was inversely associated with liver cancer.

• 1. Sugars in diet and risk of cancer in the NIH-AARP Diet

and Health Study

• 1. Sugars in diet and risk of cancer in the NIH-AARP Diet

and Health Study

Tasevska N, Jiao L, Cross AJ, et al. (2012) Conclusions:

Positive associations were established between intakes of certain sugar categories and specific types of cancer, but there were many inconsistencies between genders and a lot of statistically insignificant data. No association or inverse association was found more often than positive association. Strengths: This study was the first to investigate the association of various forms and dietary classifications of sugars with multiple malignancies. Large sample size allowed examination of rarer cancers. Limitations: The authors admit in their conclusions that there is high probability that some of the findings may have occurred due to chance, which is a common problem in analyses of this type, examining multiple comparisons. In some instances where inverse association was demonstrated, such as decreased risk of liver cancer with high intake of added fructose, there may have been an unidentified confounder.

• 2. Sugar-sweetened beverage intake and cancer

recurrence and survival in CALGB 89803

Fuchs MA, Sato K, Niedzwiecki D, et al. (2014) Overview and Methods:

Assessed association between sugar-sweetened beverage consumption on cancer recurrence and mortality by using food frequency questionnaires. Subjects: 1,011 stage III colon cancer patients

• 2. Sugar-sweetened beverage intake and cancer

recurrence and survival in CALGB 89803

Fuchs MA, Sato K, Niedzwiecki D, et al. (2014) Overview and Methods:

All subjects participated in CALGB: National Cancer Institute-sponsored Cancer and Leukemia Group B (CALGB) Food Frequency Questionnaires addressed 113 foods and had space to write in additional foods that weren’t listed. It addressed sugar sweetened beverage consumption by asking about frequency: from less than twice per month to greater than 2 times per day.

• 2. Sugar-sweetened beverage intake and cancer

recurrence and survival in CALGB 89803

Fuchs MA, Sato K, Niedzwiecki D, et al. (2014) Results:

Patients consuming more than 2 servings of sugar sweetened beverages per day had a greater risk

• r recurrence or mortality (1.67) than those who consumed sugar sweetened beverages less than

2 times per month. Rates of cancer recurrence or mortality were greater in patients that had a body mass index above 25 kg/m2 combined with decreased physical activity. There was no significant difference in whether it was soda or kool-aid as long as it was a sugar- sweetened beverage.

• 2. Sugar-sweetened beverage intake and cancer

recurrence and survival in CALGB 89803

Fuchs MA, Sato K, Niedzwiecki D, et al. (2014) Conclusions:

Strengths: Participants were from a multicenter (community and academic centers) study that represented the general population well. When the researchers accounted for confounding variables such as BMI, physical activity levels, energy factors and consuming a Westernized diet the results stayed just about the same. Limitations: There could be confounding variables that weren’t accounted for. Conclusion: Patients that have stage 3 colon cancer and consume 2 or more sugar-sweetened beverages per day are at a higher risk for developing colon cancer again or dying as a result of colon cancer than patients that consume a diet much lower in sugar-sweetened beverages.

• 3. Sucrose, High-Sugar Foods, and Risk of Endometrial

Cancer—a Population-Based Cohort Study

Friberg E, Wallin A, Wolk A. (2011) Overview and Methods:

This study used data from the Swedish Mammography Cohort, which included 61,226 women aged 40-74 years. Consumption of high-sugar foods (such as cookies and “sweet buns”) and total sucrose was examined in relation to endometrial cancer risk using incidence rate ratios (RR). A questionnaire inquiring about consumption frequency of 67 common food items as well lifestyle variables (exercise, smoking, use of supplements, etc.) was sent along with mammography screening invitations to all women residing in two counties of Sweden who were born between 1914 and 1948. Completed questionnaires were received from 66,651 women. A second questionnaire, inquiring about 96 food items, was mailed out to 56,030 members of the same group still living in the area in 1997. A total of 39,227 women completed both questionnaires. The study cohort was linked to the Swedish Cancer Register, Swedish In-patient Register, Swedish Death Register and Swedish Population Register in order to obtain complete and accurate records pertaining to cancer diagnoses, hysterectomy, death, or migration out of the study area, respectively.

• 3. Sucrose, High-Sugar Foods, and Risk of Endometrial

Cancer—a Population-Based Cohort Study

Friberg E, Wallin A, Wolk A. (2011) Overview and Methods:

“Person-years”were calculated as a unit of time measurement between events. Person-time was calculated from January 1, 1998, through December 31, 2008. Statistical analyses included 36,773 subjects, 379,760 person-years, and 304 cases of endometrial cancer. Researchers hypothesized that a link between consumption of high-sugar foods and endometrial cancer risk may exist, based on the association of endometrial cancer with insulin resistance, hyperinsulinemia, and obesity which has been previously established.

Why “sweet buns,” specifically?

The Swedish Kanelbulle is the “cousin” of the American cinnamon bun. Kanelbullar (plural form) are commonly enjoyed during fika (“fee-ka”), the daily coffee break of the Swedish. In other words, this is a food that most adults in Sweden consume on a daily basis. We have no equivalent to this in the U.S.

• 3. Sucrose, High-Sugar Foods, and Risk of Endometrial

Cancer—a Population-Based Cohort Study

Friberg E, Wallin A, Wolk A. (2011) Results:

From the original cohort of 61,226 women, 729 incident adenocarcinoma endometrial cancer cases were diagnosed. Of the 36,773 women who completed both questionnaires, 304 were diagnosed. The mean age at diagnosis was 67.6 years.The total follow up period lasted 18.4 years. Women with high intake of sucrose also had, on average, higher intakes of fat, total calories, protein, and coffee, but were less likely to have diabetes or to have ever smoked. The results of both questionnaires demonstrated that general consumption of sucrose and consumption

• f sweet buns and cookies were associated with increased risk of endometrial cancer. The association

was stronger among overweight and obese subjects. Other high-sugar foods were not significantly associated with endometrial cancer risk.

• 3. Sucrose, High-Sugar Foods, and Risk of Endometrial

Cancer—a Population-Based Cohort Study

Friberg E, Wallin A, Wolk A. (2011) Conclusions:

Total sucrose intake and consumption of sweet buns was found to be positively associated with risk of endometrial cancer, particularly in overweight or obese women. The authors speculate about the biological mechanisms responsible for this increased risk:

• A progression of hyperglycemia, insulin resistance, hyperinsulinemia, obesity, and diabetes has been

previously linked to endometrial cancer.

• Hyperinsulinemia stimulates growth of endometrial stromal cells and may also increase levels of free

estrogens, which can increase risk stimulating proliferation of endometrial cells. Hyperinsulinemia also commonly results in hypoadiponectinemia (low levels of adiponectin), which further increases risk.

• 3. Sucrose, High-Sugar Foods, and Risk of Endometrial

Cancer—a Population-Based Cohort Study

Friberg E, Wallin A, Wolk A. (2011) Strengths/Weaknesses:

Strengths include the prospective, population-based design, length of follow-up, relatively high rate of subject participation, and thoroughness of medical, migration, and death records utilized. Weaknesses include self-administered food-frequency questionnaires and the use of sucrose as the primary sweetener for beverages in Sweden, making results from this study relating to sugar- sweetened beverages largely invalid for populations consuming beverages sweetened with high- fructose corn syrup.

• 4. Dietary fructose, carbohydrates, glycemic indices and pancreatic

cancer risk: a systematic review and meta-analysis of cohort studies

Aune D, Chan DS, Vieira AR, et al. (2012) Overview and Methods:

Study design: Meta Analysis Study selection: prospective cohort, case-cohort or nested case-control Inclusion Criteria: Must investigate the association between dietary carbohydrates (excluding fiber) glycemic index (GI) or glycemic load (GL) and pancreatic cancer risk. Estimates of pancreatic cancer risk had to be available with the 95% confidence intervals in the publication Ten publications were analyzed, eight from North America and two from Europe. Eight were cohort studies and two were nested case-control.

• 4. Dietary fructose, carbohydrates, glycemic indices and pancreatic

cancer risk: a systematic review and meta-analysis of cohort studies

Aune D, Chan DS, Vieira AR, et al. (2012) Results:

No correlation between intake of total carbohydrates, sucrose, glycemic index, glycemic load and being at a higher risk for developing pancreatic cancer was found. However, higher fructose consumption in this meta analysis was shown to increase a subject’s risk of developing pancreatic cancer.

• 4. Dietary fructose, carbohydrates, glycemic indices and pancreatic

cancer risk: a systematic review and meta-analysis of cohort studies

Aune D, Chan DS, Vieira AR, et al. (2012) Conclusions:

The intake of fructose, but not total carbohydrates, sucrose, GI or GL increases the risk of pancreatic

• cancer. It is still unknown if there are specific foods or beverages associated with this risk, so further

studies need to be conducted. Strengths: Statistical power due to analyzing over 1 million subjects and 3,000 cases Limitations- Diets that are high in fructose may have other behaviors that are associated with them such as: overweight and obesity, low physical activity, smoking and higher alcohol intake. The studies that adjusted for smoking, BMI, red meat intake, and energy intake still showed that a higher fructose intake was correlated to a higher pancreatic cancer risk. The studies that adjusted for alcohol, diabetes, and physical activity showed no correlation.

• 5. Glycemic index, glycemic load, and the risk of pancreatic cancer among

postmenopausal women in the women’s health initiative observational study and clinical trial.

Simon MS, Shikany JM, Neuhouser ML, et al. (2010)

Overview and Methods:

Data were obtained from the population-based women’s health initiative (WHI) cohort, which included 161,809 postmenopausal women aged 50-79 years. Median time of follow-up was 8 years. Pancreatic cancer was identified in 332 individuals within this cohort, and of these, 287 met criteria for

• analysis. Potential subjects were excluded if they were found to have a history of pancreatic cancer or other

cancers, had unknown possible history of cancer, had unreliable FFQ results (<600 kcal or >5000 kcal per day), or had extreme BMI values (<15 or >50 kg/m2).

A validated FFQ containing 122 items was administered to measure glycemic index (GI), glycemic load, (GL), total carbohydrates, available carbohydrates (fiber subtracted), fructose, and sucrose within the three months prior to enrollment. GI values for pertinent food items were obtained from published tables and used to estimate GI and calculate GL from subjects’ FFQs.

• 5. Glycemic index, glycemic load, and the risk of pancreatic cancer among

postmenopausal women in the women’s health initiative observational study and clinical trial.

Simon MS, Shikany JM, Neuhouser ML, et al. (2010)

Overview and Methods:

Subjects were divided into quartiles for comparative analysis. Chi-square tests were used to evaluate differences in variables between cases and healthy subjects. Multivariable models adjusted for age, race, income, BMI, frequency of physical activity, history of diabetes, alcohol use, and smoking status (never, past, or current, and for past or current smokers, cigarettes per day and duration of habit). Cigarette smoking is the most important risk factor for pancreatic cancer.

The authors speculate that dietary factors which increase glucose concentration may be associated with increased risk of pancreatic cancer due to the direct relationship between blood glucose and insulin response.

• 5. Glycemic index, glycemic load, and the risk of pancreatic cancer among

postmenopausal women in the women’s health initiative observational study and clinical trial.

Simon MS, Shikany JM, Neuhouser ML, et al. (2010)

Results:

Younger women with higher BMIs were more likely to fall into the highest quartile of GL. Lower incidence of diabetes, lower alcohol consumption, and lower likelihood of smoking were additional trends seen in the fourth quartile. Following multivariable adjustment, there was no significant association between incidence of pancreatic cancer and any of the dietary factors in question. Exclusion of subjects with diabetes did not produce any notable changes in the outcomes of statistical analyses. Re-analyzation of data by BMI category did not produce any significant results.

• 5. Glycemic index, glycemic load, and the risk of pancreatic cancer among

postmenopausal women in the women’s health initiative observational study and clinical trial.

Simon MS, Shikany JM, Neuhouser ML, et al. (2010)

Conclusions:

While the authors had hypothesized that high intake of carbohydrates would be correlated with increased risk of pancreatic cancer, the findings of this study do not support an association between pancreatic cancer and GL, GI, total carbohydrates, available carbohydrates, fructose, or sucrose. Strengths: A large cohort was followed over a substantial period of time. The FFQ used was specific to the WHI cohort. Limitations: The semiquantitative FFQ was not the best tool for accurately measuring GI and GL. This study only involved women, and may not be fully applicable to men. Trends observed in association with carbohydrate intake quartiles appear to be at least in part by chance.

• 6. Sugary food and beverage consumption and epithelial ovarian

cancer risk: a population-based case-control study

King MG, Olson SH, Paddock L, et al. (2013)

Overview and Methods:

Study type: Population based-case-control study Methods: Evaluated ovarian cancer risk in relation to sugar foods and beverages and total and added sugar intakes by evaluating food frequency questionnaires from ovarian cancer patients as well as controls. There were a total of 205 cases and 390 controls Most participants were white with a college education.

• 6. Sugary food and beverage consumption and epithelial ovarian

cancer risk: a population-based case-control study

King MG, Olson SH, Paddock L, et al. (2013)

Overview and Methods:

Inclusion criteria: Women with newly diagnosed epithelial ovarian cancer, older than 21, English or Spanish speaking, residents of 6 counties in New Jersey. Control cases were the same but without cancer. Participants were excluded if they had both of their ovaries removed. All participants completed a phone interview, food frequency questionnaire and self-recorded waist and hip measurements. The number of servings of dessert foods with added sugars, non-dessert foods with added sugars, sugary drinks and sugary foods and drinks were totaled for each subject. Both total sugars and added sugars were calculated for each participant. Total sugars included sugars in fruits, veggies, milk, etc. Added sugars were considered to be added to foods during processing and preparation.

• 6. Sugary food and beverage consumption and epithelial ovarian

cancer risk: a population-based case-control study

King MG, Olson SH, Paddock L, et al. (2013)

Results/Conclusions:

Results: At first, multivariable analyses showed an increase in ovarian cancer risk for those who consumed a higher amount of total sugar foods and drinks and sugary non-dessert foods even after adjusting for age and energy intake. However, once researchers adjusted for additional risk factors this didn’t remain significant. Conclusions: There was no correlation found between ovarian cancer risk and intake of sugary foods and beverages or total and added sugar. There was no correlation found between ovarian cancer risk and intake of sugary foods and beverages or total and added sugar.

Conclusions

For optimal health, consuming sugar in excess isn’t recommended for anyone. Evidence on this topic is mixed and in many instances there has been no association or inverse association shown, which suggests results could be due to chance or confounding variables. For this reason, there is not sufficient justification to advise patients that sugar consumption promotes cancer. There are specific cases where it might be a good idea to check into the current research. For example; A patient with a BMI >25 who has stage III colon cancer should be more cautious than someone in good health about consuming more than two sugar-sweetened beverages per day. Overall, reducing intake of added sugars is a sensible dietary goal for individuals of any health status. Reducing added sugars leaves more room in the diet for nutrient dense foods that can provide adequate levels of vitamins and minerals.

References

1.Tasevska N, Jiao L, Cross AJ, et al. Sugars in diet and risk of cancer in the NIH-AARP Diet and Health Study. Int J Cancer. 2012;130(1): 159–169.

• 2. Fuchs MA, Sato K, Niedzwiecki D, et al. Sugar-sweetened beverage intake and cancer recurrence and survival in CALGB
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• 3. Friberg E, Wallin A, Wolk A. Sucrose, high-sugar foods, and risk of endometrial cancer—a population-based cohort
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• 4. Aune D, Chan DS, Vieira AR, et al. Dietary fructose, carbohydrates, glycemic indices and pancreatic cancer risk: a

systematic review and meta-analysis of cohort studies. Ann Oncol. 2012;23:2536-2546.

• 5. Simon MS, Shikany JM, Neuhouser ML, et al. Glycemic index, glycemic load, and the risk of pancreatic cancer among

postmenopausal women in the women’s health initiative observational study and clinical trial. Cancer Causes Control. 2010 December ; 21(12): 2129–2136.

• 6. King MG, Olson SH, Paddock L, et al. Sugary food and beverage consumption and epithelial ovarian cancer risk: a

population-based case-control study. BMC Cancer. 2013;13:94-106.