Reference
Mueller NT, Odegaard A, Anderson K, et al. Soft drink and juice consumption and risk of pancreatic cancer: the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev. 2010;19(2):447-455.
Design
Prospective cohort study; information on consumption of soft drinks, juice, and other dietary items, as well as lifestyle and environmental exposures, was collected through in-person interviews at recruitment.
Participants
60,524 people taking part in the Singapore Chinese Health Study
Key Findings
Drinking two or more sodas a week almost doubles a person’s risk of developing pancreatic cancer. Following these people for 14 years yielded 648,387 person-years of data and 140 cases of pancreatic cancer (PC). Individuals who consumed 2 or more soft drinks a week experienced a statistically significant increase in risk of pancreatic cancer (hazard ratio, 1.87; 95% confidence interval, 1.10–3.15) compared with individuals who did not consume soft drinks. There was no association seen between drinking fruit juice and risk of PC.
Practice implications
This is just the latest in a series of studies on the subject that have yielded sometimes conflicting and confusing results. Yet the bottom line consensus appears to be that soda or other concentrated forms of sugar, such as candy bars, do increase risk of pancreatic cancer.
Pancreatic cancer does not respond well to treatment: 5-year survival even with modern treatment is less than 5%. Therefore, prevention is the best approach. Cigarette smoking is the one accepted risk factor consistently associated with increased risk of pancreatic cancer. Type 2 diabetes also increases risk, which led to a theory that producing high levels of insulin might somehow lead to malignant transformation of pancreatic cells.
In most cancers, the cells that become cancerous have been somehow overworked, irritated, or in some way abused before becoming cancer cells. They have been pushed by something to grow faster, work harder, secrete more or in some manner live harder lives. Estrogen pushes both breast and uterine cells to become cancerous. Testosterone pushes prostate cells to become prostate cancer. Infections push lymph cells to become lymphoma. This theory about pancreatic cancer suggests that high sugar intake pushes the pancreas.
Diabetes has been associated with pancreatic cancer for decades. A study on Seventh Day Adventists published in 1988 reported that “prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer.”1
A Kaiser Permanente study published that same year found that while cigarette smoking increased risk of pancreatic cancer by a factor of 2.5, people who had been treated for diabetes had 4.5 times the risk. (Smoking: relative risk, 2.5; 95% confidence interval, 1.3–4.7. Diabetes: relative risk, 4.5; 95% confidence interval, 1.2–16.7)2
A Dutch paper published in 1990 that analyzed data on 164 patients with pancreatic cancer found “a significant, positive association between pancreatic cancer and past habitual intake of simple sugars.” (OR 1.95; 95% confidence interval, 1.24–3.07). This led the study authors to suggest that “the development of exocrine pancreatic carcinoma is positively related to past habitual intake of total energy, total carbohydrates, and simple sugars.”3
A 1991 Australian paper that analyzed the habits of 104 people who developed PC also found a link to sugar consumption. “For the top quartile of refined sugar intake, the estimated relative risk was 2.21 (95% confidence interval, 1.07–4.55).”4
A December 1995 study that looked at 179 cases of PC in French speaking Canadians found a similar effect of sugar consumption. Again, high sugar consumption nearly tripled risk. Of interest in this paper was the pronounced effect of cooking with firewood, a habit that increased relative risk by a factor of almost 5, while cooking in a pressure cooker lowered risk to one-third the average.5
Sweetened carbonated drinks, what we call soft drinks, or soda, are a major source of simple sugars in western diets. As such, soda consumption provides a measure of overall sugar consumption.6 Soda consumption is associated with hyperglycemia and hyperinsulinemia, obesity, and type 2 diabetes.7,8
Rates of developing pancreatic cancer have plateaued and are stable in the United States, but they are rising among Chinese men and women in Singapore.9 From 1968 to 1998, they have almost doubled (going from 3.7 to 5.4 per 100,000 for men and 1.5 to 3.4 per 100,000 for women). One explanation for this increase is the shift toward a more western diet and increased consumption of sugar and sugar-sweetened sodas. It may be that during this transition period between traditional diets and western diets, the effect of soda consumption is more pronounced. Soda may be adopted into the diet while traditional foods and recipes still comprise the basic diet.
On the other hand, as soda consumption increases so do other behaviors linked to higher risk of pancreatic cancer. For example in the Mueller study, people who drank more soda also consumed more red meat, total fat, sugar, candy, and alcohol.
They smoked more, exercised less, and were more likely to become diabetic. Is soda the cause of the increased risk, or is it just a marker of overall poor lifestyle?
They smoked more, exercised less, and were more likely to become diabetic. Is soda the cause of the increased risk, or is it just a marker of overall poor lifestyle? The intricate dissection of this data using statistical tools is a delicate task. Simply gathering data on so rare a cancer is itself a challenge.
In the last 5 years, 4 other prospective cohort studies have been published that looked at this same equation of soda or sugar consumption and whether it is tied to pancreatic cancer risk. Results from the current Mueller paper are consistent with 3 out of 4 of these earlier studies. One other study included fruit juice and found a positive association between juice intake and PC risk; this current study did not find an association.
For their 2005 paper, Schernhammer and researchers from Harvard used data from 2 large cohorts—the Nurses’ Health Study and the Health Professionals Follow-up Study—comprising 88,794 women and 49,364 men. These cohorts over the course of 20 years follow-up yielded data on 379 cases of pancreatic cancer. Schernhammer’s analysis found that the women who consumed more than 3 sodas a week had a 57% greater risk of pancreatic cancer than women who drank 1 or fewer sodas per month. (RR, 1.57; 95% CI, 1.02–2.41; P for trend = 0.05). No association was found in the 174 men who developed pancreatic cancer.10
In November 2006, the American Journal of Clinical Nutrition published a paper by Larsson, et al, analyzing Swedish dietary data from a cohort of 77,797 people who were followed for 7 years, 131 of whom developed pancreatic cancer. Those who drank 2 or more soft drinks per day had a 93% increased risk of pancreatic cancer. (OR 1.93 (1.18, 3.14; P for trend = 0.02)11,12
A November 2007 study conducted by Nothlings and fellow researchers from the University of Hawaii analyzed data for 162,150 participants in the Hawaii-Los Angeles Multiethnic Cohort Study to investigate associations between glycemic load, dietary carbohydrates, sucrose, fructose, total sugars, and added sugars and the risk of pancreatic cancer. During 8 years of follow-up, 434 pancreatic cancer cases occurred within the group. Again the results, though suggestive, contradict other studies, at least in part. The risk of PC increased with higher intakes of total sugars, fructose, and sucrose. The association with fructose was significant when the highest and lowest quartiles were compared (relative risk: 1.35; 95% CI: 1.02, 1.80; P for trend = 0.046). An almost identical association was found with high fruit and juice intake (1.37; 1.02, 1.84; P for trend = 0.04), but no association was seen with soda intake. The researchers concluded that “high fructose and sucrose intakes may play a role in pancreatic cancer etiology. Conditions such as overweight or obesity in which a degree of insulin resistance may be present may also be important.”13,14
The Bao study published in 2008 is the one report that did not find an association between sugar and PC, despite the fact that it was the largest of the studies. Rather than soda, the researchers calculated the total consumption of added sugar and sugar-sweetened foods and beverages, examining data from 487,922 men and women, calculating total added dietary sugar intake. During 7.2 years of follow-up, 1,258 pancreatic cancer cases were found within the group. The lowest sugar consumers averaged about 3 tsp/day, while the high consumers averaged almost 23 tsp/day. No statistically significant difference in risk was seen between these 2 groups. Thus these results did not support the sugar hypothesis.15,16
In August 2009, another study reported a positive but still confusing association. Chan and colleagues from the University of California in San Francisco reported in the journal Cancer Causes and Control on a comparison of the dietary habits of 532 people who developed PC with people who didn’t. “Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk” that ranged from an overall risk of 1.9 for total sweets to 3.3 for candy bars, but the study did not find sweets to be consistently associated with risk among women. In contrast to other soda studies, they also reported that “sweetened beverages were not associated with increased pancreatic cancer risk.” But to confuse things further the authors found “low-calorie soft drinks were associated with increased risk among men.”17
In November 2009 an Italian study was published that once again supported a link between sugar consumption and pancreatic cancer. Polesel, et al, worked with data from 326 patients with pancreatic cancer comparing them to 652 control patients. Comparing the diets of the 2 groups they found that “frequent meat consumption was associated to a twofold increased risk of pancreatic cancer (95% CI, 1.18–3.36). Added table sugar (OR = 2.23; 95% CI, 1.34–3.71) and potatoes (OR = 1.79; 95% CI, 1.12–2.86) were related to pancreatic cancer.” This led the authors to conclude that “the increased risk for table sugar suggests that insulin resistance may play a role in pancreatic carcinogenesis.”18
Thus the Mueller study does not stand alone but is one of a series of studies that have parsed out this relationship between sugar and pancreatic cancer. If we are to accept these findings, though, we need an explanation for this relationship.
There are 2 types of pancreatic cancer, endocrine and exocrine; endocrine tumors develop in the hormone-producing tissues for secretion into the blood, while exocrine cancers develop from the tissues that make digestive enzymes for secretion into the intestine. 95 percent of pancreatic tumors develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.19 These exocrine-derived tumors are the focus of this discussion.
The endocrine and exocrine parts of the pancreas are not independent of each other; instead, they are functionally related, and the endocrine gland profoundly affects the pancreas’s digestive activities. Blood and insulin are carried from insulin-producing cells to exocrine cells in what has been named the insulin-pancreatic acinar axis. Insulin regulates the exocrine function of the pancreas. Exocrine cells are exposed to insulin concentrations that are 20-fold higher than in general circulation. Insulin has an effect on these cells, increasing cell division and stimulating production of amylase.20,21 These high insulin levels may increase free insulin-like growth factor (IGF) by lowering levels of IGF-binding proteins. Low levels of IGF-binding proteins are suggested in some research to be risk factor for pancreatic cancer.22 However, not all studies support this idea; an August 2009 paper found no link between IGF-1 or IGF-binding proteins and PC.23
The Mueller paper found no association between fasting plasma insulin levels and pancreatic cancer risk. “This suggests that postprandial insulin may be a better measure for the association with cancer risk than fasting insulin levels and is consistent with the independent role of soft drink consumption in the development of pancreatic cancer.”24 In other words, it may be the surge of insulin produced after eating concentrated sugars that is the problem.
Abandoning these soda studies for a moment, this idea that elevated insulin levels increase cancer risk is supported by a paper published in September 2009 in Diabetologia. Currie and colleagues at Cardiff University looked for confirmation of this insulin theory by looking at the effects of different blood sugar–lowering treatments on type 2 diabetics.
They analyzed a retrospective cohort of 62,809 people who developed diabetes after age 40 and who were treated with either oral agents or insulin. These patients were divided into 4 groups according to whether they received monotherapy with metformin or sulfonylurea, combined therapy (metformin plus sulfonylurea), or insulin. The outcome measures were progression to any solid tumor, or cancer of the breast, colon, pancreas, or prostate. Metformin monotherapy carried the lowest risk of cancer. Adding metformin to insulin reduced progression to cancer. Compared with metformin, insulin therapy increased the risk of colorectal or pancreatic cancer. Sulfonylureas were associated with a similar pattern of risk as insulin. It appears anything that increases insulin levels increased risk of some cancers, especially pancreatic cancer.25
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