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Tuesday, October 04, 2011

From a Colorado colleague: Soda increases Pancreatic Cancer Risk

Pancreatic cancer and soda consumption:
Jacob Schor ND FABNO
February 13, 2010

An odd coincidence in timing:
Perhaps it is because soda and candy have been a big story in Colorado legislative news over the last few months, that an article in an obscure epidemiology journal caught my attention this past week.  Back in November 2009 Colorado’s currently democratic leadership announced plans to add a 2.9% tax to carbonated beverages and candy as part of a comprehensive plan to balance the state budget.  The bill to turn Governor Ritter’s soda tax proposal into law was passed by the Colorado Senate just a few days ago. The lead up debate to this vote brought forth vocal opponents that made it apparent that many people believe unfettered access to soft drinks is a fundamental right guaranteed in the Constitution.

Coincident with these Colorado legislative debates, but unmentioned, is a fascinating paper by Noel Mueller et al. that appeared in the February issue of Cancer Epidemiology, Biomarkers & Prevention.  According to their analysis, drinking two or more sodas a week almost doubles a person’s risk of getting pancreatic cancer.

Their data was collected from a prospective cohort made up of 60,524 people who are taking part in the Singapore Chinese Health 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.
Following these people for 14 years yielded 648,387 person-years of data and 140 cases of pancreatic cancer (PC). Individuals who consumed two 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.

A hazard ratio of 2.0 would mean soda drinkers were twice as likely to get pancreatic cancer.  This ratio of 1.87 is just a little less than 2.0.

Background is essential to understand the results of this study.   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.

The first thing we have to understand with PC is that it’s one of the bad cancers; five-year survival even with modern treatment is less than 5%.  Treatment does little good; a better approach is to focus on prevention.  Cigarette smoking is the one accepted risk factor consistently associated with increased risk of pancreatic cancer.  Type 2 diabetes also increases risk.  This 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 prior to 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. Chronic inflammation pushes colon cancer cells, etc.  This theory about pancreatic cancer suggests that high sugar intake pushes the pancreas.   Granted, this is a vast oversimplification of both a complex process and a complicated hypothesis, but it works for my simple mind.

Diabetes has been associated with pancreatic cancer for decades. A study on Seventh Day Adventists published in 1988 reported that, “A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer….”    Overwork cells or abuse them and they aren’t happy.
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).)

A Dutch paper published two years later 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, …”   

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).”

[Of course sugars aren’t the only dietary culprit in the pancreatic cancer story.  High fat diets have also been identified as a factor. A November 1993 study reported that high fat foods tripled risk.    ]
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 1/3 the average.   

Sweetened carbonated drinks, what we call soft drinks, or soda, are a major source of simple sugars in western diets and as such, soda consumption provides a measure of overall sugar consumption. [16]   Soda consumption is associated with hyperglycemia and hyperinsulinemia, obesity and type 2 diabetes.   

Let us return to the current study by Mueller and colleagues.  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. 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 that 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?  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 five years four 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. (Schernhammer, Larsson, Nothlings, Bao)  Results from the current Mueller paper are consistent with three out of four 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.

Eva Schernhammer and researchers from Harvard used data from two large cohorts, the Nurses' Health Study and the Health Professionals Follow-up Study, comprising 88,794 women and 49,364 men for their 2005 paper. 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 one or less sodas a 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.

In November 2006, the American Journal of Clinical nutrition published a paper by Susanna 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 a day had a 93% increased risk of pancreatic cancer. (OR1.93 (1.18, 3.14; P for trend = 0.02)   

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, at least in part, other studies. 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.”

The Bao study published in 2008 is the one report that did not find an association between sugar and PC.  This is despite the fact that it was the largest of the studies.  Rather than soda they 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 difference in risk was seen between these two groups.  We should clarify; no statistically significant difference was seen.  The low sugar consumers had a relative risk of 0.85 compared to the high sugar eaters but this did not reach statistical significance. Thus these results did not support the sugar hypothesis.   

Just a year later in August 2009, another study reported different results, a positive but still confusing, association.  June 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 in this study,  “…Sweets were not 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,  “… low-calorie soft drinks were associated with increased risk among men…”  

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 two 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.”  Leading them to conclude that, “The increased risk for table sugar suggests that insulin resistance may play a role in pancreatic carcinogenesis.”
Thus the results of the Mueller study do not stand-alone but are 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 to explain this relationship.

There are two types of pancreatic cancer, endocrine or 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.  “Of pancreatic tumors, 95% develop from the exocrine portion of the pancreas, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.”    These exocrine derived are the focus of this discussion.

“It is tacitly assumed that the endocrine and exocrine parts of the pancreas are independent of each other, almost as though they were anatomically related by some sort of celestial coincidence.”  But this is not the case.  Instead, “…the two components are functionally related, and that the endocrine gland exerts a profound effect upon the digestive activities of the organ.”  Blood and with it, 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.      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.   

[It should be noted that not all studies support this idea; an August 2009 paper found no link between IGF-1 or IGF-binding proteins and PC.  ]

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….”   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 four 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. In comparison, the adjusted HR was 1.08 (95% CI 0.96-1.21) for metformin plus sulfonylurea, 1.36 (95% CI 1.19-1.54) for sulfonylurea monotherapy, and 1.42 (95% CI 1.27-1.60) for insulin-based regimens. Adding metformin to insulin reduced progression to cancer (HR 0.54, 95% CI 0.43-0.66). …. Compared with metformin, insulin therapy increased the risk of colorectal (HR 1.69, 95% CI 1.23-2.33) or pancreatic cancer (HR 4.63, 95% CI 2.64-8.10),…..  Sulfonylureas were associated with a similar pattern of risk as insulin.”  It appears anything that increases insulin levels whether it is oral hypoglycemic drugs or actual insulin increased risk of some cancers, especially pancreatic cancer risk.

Back to Colorado’s ‘Soda Tax’ for a moment.  One of the arguments against taxing soda was that the price increase would dissuade consumers from purchasing it and therefore harm Colorado businesses and beverage dealers leading to job losses. Ignorant as I am about the economics of junk food marketing, I find it difficult to believe that a 2.9% price increase would influence anyone’s purchase decision to such an extent.
Given the concerns raised by these studies regarding the health impact soda has, the tax sounds far too low as it will do little to shift consumption patterns.   Perhaps my views are swayed by the task of sitting with people every day who ask me why they have cancer.  A better argument against the soda and candy tax might be that they will effectively lower consumption and eventually cut pancreatic cancer incidence by half leading to unemployment among oncologists. We should be so lucky!

http://www.gfdoctor.com/?tag=pancreaticcancer

A version of this newsletter is posted on our website with abstracts of all or almost all of the studies mentioned.

http://denvernaturopathic.com/sodaandPC.htm

Dr. Jean M. Layton
1329 King Street
Bellingham WA 98229

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