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Cancer Prevention

physician assistant

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Introduction:

General cancer prevention may be attempted by using the information here to select general dietary and lifestyle interventions which may be associated with a lower incidence of many types of cancer. It is well documented that tobacco or alcohol use is associated with various cancers and these topics will therefore not be discussed in detail. This information includes data that shows lifestyle habits and interventions associated with reduction of general cancer incidence. For information containing valuable data on specific types of cancer, please see those individual sections.

 

Family history cancer risk due to genetics vs. shared behaviors:

Family history of cancer usually refers to a link between first degree relatives including siblings, parents or grandparents but more distant links of cancer between non-first degree family members is also possible. According to Bostean, et al, a patient with a family history of cancer may have a cancer risk either due to a genetic factor or a family shared behavior. Family shared behaviors might include dietary habits, substance abuse, tobacco use, family-associated environmental exposure or occupational exposure to chemicals. There are especially strong genetic links seen between family members with colorectal cancer and breast cancer. (1)

 

Environmental and chemical carcinogens:

Wogan et al discussed in an article that there are several concerning environmental and chemical carcinogens. Avoid smoking- DNA damage by carcinogens in tobacco may lead to lung cancer, bladder cancer and other cancers. Heterocyclic amines formed in meats heated over 180 degrees Celsius (about 400 degrees Fahrenheit for extended periods) are linked to breast, stomach and colon cancer in epidemiological studies. Liver cancer risk is elevated in patients with hepatitis infection exposed to aflatoxin produced by mold in foods originating from Asia and Africa. (2)

 

Exercise and Cancer:

Physical activity and lung cancer:

Alfano et al. completed a study, drawn from the beta-Carotene and Retinol Efficacy Trial, a lung cancer chemoprevention trial, examining physical activity and lung cancer incidence and mortality among 7,045 (59% male) current and former smokers with a mean age of 63 years. Compared to non-active participants, an increase in physical activity resulted in a 14% decreased risk for all-site cancer among men; a 16% decrease risk for lung cancer and a 15% decrease for cancer mortality was seen among younger participants only. Among women, they reported no association between physical activity and lung cancer incidence. Women who were physically active had a 31% decreased risk of lung cancer mortality compared with women who were not physically active. (3)

 

Aerobic exercise, a low fat, high fiber diet, and cancer:

Aerobic exercise and a low fat, high fiber diet made the blood much less hospitable to prostate cancer cells in vitro. A study authored by Barnard, et al. consisted of using the blood from 3 different groups of 51 to 64 year old males to treat cultured prostate cancer cells in the lab. They compared the blood placed in petri dishes with prostate cancer cells from 3 different groups. The groups included an exercise group that did a consistent exercise program for at least 10 years, a diet plus exercise group who did a consistent diet and exercise program for at least 10 years, and a placebo group. The diet and exercise group were part of a “Pritikin” program and ate low fat, high fiber and complex carbohydrates along with exercise 4-6 days per week. The exercise group exercised for 1 hour per day 5 days per week at a University program in Nevada but did not have any diet program. The placebo subjects were sedentary with poor dietary intake and felt to be at risk of prostate cancer. The blood from the diet plus exercise group caused a significantly greater rate of apoptosis of cancer cells and less growth rate in cancer cells in vitro than the exercise alone or placebo groups. (4)

 

Low fat, high fiber diet, exercise, and breast cancer:

Serum markers of breast cancer in vivo decreased, and apoptosis in breast cancer cells increased in vitro after diet and exercise. A study involving 38 overweight or obese postmenopausal women adhered to a low-fat (10-15% kcal from fat), high-fiber (30-40 g per 1,000 kcal per day) diet, and participated in a daily exercise class for 2 weeks.  The diet and exercise was found to reduce several serum markers for breast cancer including estrogen, obesity, insulin and insulin-like growth factor-I (IGF-I), even while subjects remained overweight or obese. The in-vitro analysis used serum drawn from the study group before and after the 2 week intervention and placed it with cancer cells. It was found that the growth in different types of breast cancer cell lines was reduced by 6.6-18.5%. Cell death of several different cell types of breast cancer also increased by 20-30% after the intervention. (5)

 

Beta-carotene and cancer:

Beta-carotene in foods vs. supplements and cancer risk: Cancer risk is lower in those who consume beta-carotene containing foods but not beta-carotene supplements according to the National Research Council, Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. (6)

High blood concentrations of beta-carotene and other carotenoids, plant pigments found in carrots, sweet potatoes, spinach, kale, collard greens, papaya, bell peppers, tomatoes, have been linked to a lower risk of cancer, especially lung, mouth, throat, and cervical cancers.

A blood beta-carotene concentration less than 0.28 micromol/L has been linked with a higher risk of several cancers, while a concentration of more than 0.28 to 0.37 micromol/L have been associated with a reduced risk of several cancers in prospective blood concentration studies. However, three other large randomized studies reported no cancer benefit from beta-carotene supplements given at 20, 30, or 50 mg/d for 4 to 12 years.

Beta-carotene supplements are not advised among healthy individuals, unless they suffer from or are at risk of vitamin A deficiency. Beta-carotene supplementation results in a greater increase of beta-carotene blood concentration than beta-carotene rich foods. A 20 mg/d supplement of beta-carotene is associated with blood concentrations high enough to increase a patient’s risk of lung cancer, while the same quantity obtained from foods was not associated with lung cancer risk. Additionally, 30 mg/d of beta-carotene supplement was associated with blood concentrations 5 times greater than that of 29 mg/d of beta-carotene from carrots.

The consumption of 5 or more daily servings of fruits and vegetables is recommended by “National Cancer Institute’s Five-A-Day for a Better Health program” and “Canada’s Food Guide for Healthy Eating.” Eating a variety of 5 fruits and vegetables per day provides the individual with about 5.2 to 6 mg/day of food based beta-carotene. This allows plasma carotenoid levels to rise above a range represented in studies which were associated with a lower risk of cancer and all-cause mortality compared to those with a lower food based carotenoid levels.

 

The Beta-Carotene and Retinol Efficacy Trial (CARET):

The Beta-Carotene and Retinol Efficacy Trial (CARET), showed that among 18,314 men and women who smoked heavily or were exposed to asbestos, daily intake of 30 mg (100,000 IU) of beta-carotene and 25,000 IU vitamin A failed to decrease the risk of cancer. The study was stopped early because it showed that beta-carotene/vitamin A takers who were heavy smokers, ex-smokers or asbestos workers were showing a 28% increased risk of lung cancer in smokers (versus placebo) and a 17% more likely chance of dying, mostly of lung cancer or heart disease.  Results of a 6-year follow-up of study participants showed that compared to the placebo or no intervention group, participants who had taken the intervention had a 12% and 8% increase in relative risk of lung cancer and all-cause mortality among the intervention group, respectively. They found that women were more affected by the supplements with a larger relative risk of lung cancer mortality (1.33 versus 1.14; P = .36), and all-cause mortality (1.37 versus 0.98; P = .001) than males. (8)

 

Beta carotene levels and mortality risk:

Intake of vegetables containing beta carotene was associated with a lower risk for all causes of death including cancer but no benefit was seen with taking beta-carotene supplements. Greenberg ER et al tested beta carotene levels in subjects prior to being randomized to take beta carotene supplements. Subjects with an intial beta carotene level of 0.34 to 0.52 umol/L had a 51% less risk of dying from cancer when compared to subjects with the lowest intial beta carotene levels of under 0.21 umol/L. Those subjects with an intitial beta carotene level of over 0.52 umol/L had a lower risk of death from all causes. There was no reduced risk of disease or mortality benefit in subjects who took beta carotene supplements in pill form. (7)

 

Required amount of beta carotene intake to reduce mortality:

According to Martini et al in the University of Minnesota Cancer Prevention Research Unit Feeding Studies, an intake of 5 mg per day of beta carotene from food sources was required to establish beta carotene levels to a plasma level of 0.37 umol/L. When food based beta carotene was consumed in amounts over 42 mg per day, levels increased to 0.83 umol/L. (9)

 

Concentration of beta-carotene in foods:

Common highest beta-carotene containing foods (mcg):

Carrot juice, canned, 1 cup                                                               21955 mcg
Pumpkin, canned, without salt, 1 cup                                            17003 mcg
Sweet potato, cooked, baked in skin, without salt, 1 potato           16803 mcg
Sweet potato, cooked, boiled, without skin, 1 potato                     14733 mcg
Spinach, frozen, cooked, boiled, drained, without salt, 1 cup        13750 mcg
Carrots, cooked, boiled, drained, without salt, 1 cup                    12998 mcg
Spinach, canned, regular pack, drained solids, 1 cup                  12585 mcg
Sweet potato, canned, vacuum pack, 1 cup                                 12215 mcg
Carrots, frozen, cooked, boiled, drained, without salt, 1 cup        11971 mcg
Collards, frozen, chopped, boiled, drained, w/o salt, 1 cup          11591 mcg
Kale, frozen, cooked, boiled, drained, without salt, 1 cup                11470 mcg
Spinach, cooked, boiled, drained, without salt, 1 cup                    11318 mcg
Sweet potato, canned, syrup pack, drained solids, 1 cup                10782 mcg
Kale, cooked, boiled, drained, without salt,1 cup                          10625 mcg
Turnip greens, frozen, boiled, drained, without salt, 1 cup              10593 mcg
Mustard greens, cooked, boiled, drained, without salt, 1 cup        10360 mcg
Vegetables, mixed, canned, drained solids, 1 cup                         9242 mcg
Carrots, raw, 1 cup                                                                          9114 mcg
Collards, cooked, boiled, drained, without salt, 1 cup                   8575 mcg
Carrots, canned, regular pack, drained solids, 1 cup                     7783 mcg
Pie, pumpkin, prepared from recipe, 1 piece                                   7366 mcg
Beet greens, cooked, boiled, drained, without salt, 1 cup              6610 mcg
Turnip greens, cooked, boiled, drained, without salt, 1 cup            6588 mcg
Carrots, raw, 1 carrot                                                                       5965 mcg
Squash, winter, all varieties, cooked, baked, without salt, 1 cup    5726 mcg
Pumpkin, cooked, boiled, drained, without salt, 1 cup                   5135 mcg
Cabbage, chinese (pak-choi), boiled, drained, w/o, salt,1 cup        4333 mcg
Dandelion greens, cooked, boiled, drained, without salt, 1 cup        4137 mcg
Sweet potato, cooked, candied, home-prepared, 1 piece               4051 mcg
Vegetables, mixed, frozen, boiled, drained, w/o salt, 1 cup `         3789 mcg
Lettuce, butterhead (boston and bibb types), raw, 1 head             3239 mcg
Melons, cantaloupe, raw, 1 cup                                                         3232 mcg
Lettuce, cos or romaine, raw, 1 cup                                                   2927 mcg
Soup, chunky vegetable, canned, ready-to-serve, 1 cup                 2875 mcg
Lettuce, green leaf, raw, 1 cup                                                           2488 mcg
Apricots, canned, juice pack, skin, solids and liquids, 1 cup            2464 mcg
Peppers, sweet, red, raw, 1 cup                                                         2420 mcg
Tomato products, canned, paste, without salt added, 1 cup          2361 mcg

Adapted from: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at:https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w321.pdf and http://www.nal.usda.gov/fnic/foodcomp/Data/HG72/hg72_2002.pdf

 

Oral antioxidant supplementation and mortality:

A meta-analysis that included 78 randomized clinical trials was conducted to determine the relationship of oral antioxidant supplementation (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) and mortality. Mean duration of supplementation was 3 years. When all of the trials were combined, and the analysis that is typically used when similarity is present was conducted (fixed-effect model), antioxidant use did slightly increase mortality. When the trials with low risks of bias were considered, the patients consuming the antioxidants had a 4% higher risk of death compared to those taking placebo or no intervention (relative risk [RR]=1.04). The increased risk of mortality was significantly associated with use of beta-carotene (death rate: 13.8% on supplement vs 11.1% on placebo; RR=1.05) and vitamin E (12.0% vs 10.3%; RR=1.03) and possibly vitamin A, though the relationship was not significant with a 14.0% death rate among those taking vitamin A compared to a 13.6% death rate among placebo subjects. The current evidence does not support the use of these antioxidant supplements in the general population or in patients with various diseases. (11)

 

U.S. Preventive Services Task Force (USPSTF) and beta-carotene supplements:

For the prevention of cancer or cardiovascular disease, the U.S. Preventive Services Task Force (USPSTF) recommends against the use of beta-carotene supplements, alone or in combination. According to the USPSTF, the is insufficient evidence to recommend for or against the use of vitamins A, C, or E supplements or multivitamins with folic acid or antioxidant combinations for the prevention of cancer or cardiovascular disease. (12)

 

Beta-carotene in foods vs. supplements:

The studies mentioned thus far on beta-carotene suggest a lower risk of mortality stems from beta carotene intake from food sources but not beta-carotene supplements. The benefit may also come from other substances in the vegetable food source and not necessarily the beta carotene itself.

 

Calcium and cancer:

Calcium, vitamin D, and cancer risk: Calcium together with vitamin D supplements have been linked with a decrease in the relative risk of various cancers in women excluding skin cancers. A population-based randomized 4-year study conducted in Nebraska enrolled 1179 women aged 55 years and older, with no known cancer. Participants were randomly assigned to 3 groups: 1) Placebo (calcium placebo plus vitamin D placebo, n=266); 2) calcium-only (1400 mg calcium citrate or 1500 mg calcium carbonate plus vitamin D placebo, n=416); and Calcium + D (1000 IU [25 mcg] vitamin D plus calcium [as above], n=403). Serum samples were analyzed for levels of 25(OH)D, vitamin D, at baseline and then yearly. Study results found 50 women developed non-skin cancer during the study: 13 in the first year, and 37 during the second to fourth years. The relative risk (RR) for the calcium + D group was 0.232 (confidence interval [CI], 0.09–0.60; P<.005), and the RR for the calcium-only group was 0.587 (95% CI, 0.29–1.21; P=.147) compared with the placebo group. Increasing the dose of vitamin D from the current standard of 400–600 IU per day to 1000 IU per day may lower future risk of cancer in women older than age 55 who do not get adequate vitamin D from sun exposure or diet. The conclusion of the author was that an improvement of nutritional status with calcium and vitamin D significantly lowers cancer risk. (13)

 

Calcium and risk of colon cancer:

In a meta-analysis by Carroll C. et al, 3 trials showed a reduction of recurrence of colon adenomas for subjects who took 1200 – 2000 mg per day of a calcium supplement, but no decrease in risk for those with advanced adenomas. Also as part of the meta-analysis, 2 trials were found to have no benefit of calcium in those without increased risk of colorectal cancer. (14)

Shaukat A et al reviewed 3 randomized controlled trials (1,485 patients) and found that calcium supplementation was associated with a significant 20% reduction in the risk of recurrence of colorectal adenomas compared with placebo. (15)

Palacios C et al found that subjects with a median of 1180 mg per day of calcium whether from dietary calcium intake or calcium from supplements as opposed to a median of 1036 mg per day had less colorectal neoplasia. (16)

 

Excess calcium intake and cancer:

Excess calcium intake and the risk of prostate cancer: Rodriguez C et al evaluated a cohort of over 65,000 men in the United States over a period of 6-7 years revealed that intake of calcium over 2000 mg per day in the form of dietary and supplement intake was associated with a moderate increase in risk of prostate cancer. The risk of prostate cancer was not increased with diary intake. There was also no increase in risk of prostate cancer with moderate or low levels of dietary calcium intake. (17)

More on calcium and prostate cancer risk: Chung et al reviewed calcium and prostate cancer risk as part of a systematic review of health outcomes. He found that a number of studies reported that high calcium intakes were associated with an increased risk of prostate cancer. (18)

 

Consumption of dairy, calcium, vitamin D, and prostate cancer risk:

Consumption of dairy products, calcium, and vitamin D showed no increase in the risk of prostate cancer in this review and meta-anlaysis of 45 observational studies. Cohort studies demonstrated no link between dairy or milk consumption and increased risk of prostate cancer nor did case control studies of calcium intake. Additionally, dietary intake of vitamin D was not correlated with increased prostate cancer risk. The study did find that as calcium intake from food increased, the risk of prostate cancer decreased across all races. (19)

 

Calcium from vegetables and prostate cancer risk:

Butler LM complicated the understanding of the calcium and prostate cancer link when the study outcome found that moderate intakes of calcium from vegetables resulted in a moderately higher prostate cancer risk for subjects with a body mass index below 22.9. (20)

 

Calcium and risk of prostate cancer:

For the subject of prostate cancer, the analysis of the data becomes more complicated as more studies are included. Therefore, as an older male with the goal to reduce prostate cancer risk, an approach of maintaining an adequate calcium intake from food is supported by the majority of the research. Calcium supplements should be avoided by middle aged to older men.

 

Calcium and breast cancer:

Chung, et al reviewed a number of studies on health outcomes by subjects which consumed calcium and vitamin D. It was found that adequate calcium intakes in premenopausal women was associated with a decreased risk of breast cancer. (21)

 

Vitamin D and cancer:

Vitamin D and cancer mortality:

Investigators followed a total of 1,194 men over a median duration of 12.7 years in a longitudinal study looking at the link between blood levels of vitamin D and mortality. They looked at vitamin D levels and cancer-related as well as all-cause mortality. There was a clear U-shaped curve when looking at the relationship between vitamin D levels and all-cause mortality along with cancer-related mortality, meaning the risk of mortality was significantly increased at both low and high blood levels of vitamin D. In this study, the range with the lowest mortality was about a vitamin D concentration of 24 to 34 ng/ml (60 to 85 nMol/L), which approximately translates to a vitamin D dose of 2000 IU/d. In general, the biggest drop in overall death rates were seen when subjects went from being vitamin D deficient to reaching adequate levels. However, too much vitamin D translated into a gradual increase of mortality rate with cancer deaths rising significantly for the highest levels of vitamin D intake. Overall mortality was increased by 50–60% among subjects in the lowest 10% and highest 5% of the vitamin D distribution. The ideal vitamin D dose according to findings in this study is 2000 IU per day for adults. (22)

 

Vitamin D and cancer risk:

Vitamin D is important for reducing the risk of many cancers. A report by the Institute of Medicine (IOM) and the Endocrine Society’s Clinical Practice Guidelines tripled the amount of vitamin D required for most children and adults. The Endocrine Society’s Clinical Guidelines for vitamin D concluded that vitamin D deficiency be defined as a 25(OH)D < 20 ng/ml, insufficiency as a 25(OH)D of 21–29 ng/ml and sufficiency as a 25(OH)D of 30–100 ng/ml. For preventing and treating vitamin D deficiency the Guidelines recommended vitamin D intake should be: children < 1 y 400-1,000 IU/d, children 1-18 y 600-1,000 IU/d and adults 1,500-2,000 IU/d to maintain 25(OH)D concentrations of 40–60 ng/ml.  Upper limits of vitamin D intake were also set as follows: 2000 IU/day for children up to age 1 year; 4000 IU/day for children aged 1 – 18 years, and up to 10,000 IU/day for adults aged 19 years and older. The IOM report concluded that dietary and supplemental vitamin D intake is adequate to satisfy both children and adult, but their study suffered from serious flaws. A study (Moore et al) suggests that neither children nor adults in the US are obtaining the new RDA for vitamin D. Among women vitamin D intake from food was 156–208 IU/d and with supplements 244–324 IU/d. For men, corresponding values were 208–320 IU/d and 308–392 IU/d. There is no evidence that there is a downside to increasing vitamin D intake in children and adults, with the exception of those with chronic granuloma forming disorder or lymphoma in which high vitamin D levels may occur resulting in high calcium levels. (23)

 

Vitamin D and cancer risk in older women:

A population-based randomized 4-year study conducted in Nebraska enrolled 1179 women aged 55 years and older, with no known cancer. Participants were randomly assigned to 3 groups: 1) Placebo (calcium placebo plus vitamin D placebo, n=266); 2) calcium-only (1400 mg calcium citrate or 1500 mg calcium carbonate plus vitamin D placebo, n=416); and Calcium + D (1000 IU [25 mcg] vitamin D plus calcium [as above], n=403). Serum samples were analyzed for levels of 25(OH)D, vitamin D, at baseline and then yearly. Study results found 50 women developed non-skin cancer during the study: 13 in the first year, and 37 during the second to fourth years. The relative risk (RR) for the calcium + D group was 0.232 (confidence interval [CI], 0.09–0.60; P<.005), and the RR for the calcium-only group was 0.587 (95% CI, 0.29–1.21; P=.147) compared with the placebo group. Increasing the dose of vitamin D from the current standard of 400–600 IU per day to 1000 IU per day lowers future risk of cancer in women older than age 55 who do not get adequate vitamin D from sun exposure or diet. (24)

 

Vitamin C and cancer:

Vitamin C and cancer related  mortality: Loria and colleagues found an association between low blood ascorbate (vitamin C) levels and an increased risk of dying overall and from cancer, among men. Compared to men with high ascorbate blood concentraions (73.8 micromol/L or greater), men with low ascorbate blood concentrations (less than 28.4 micromol/L) have a 57% increased total mortality risk and a 62% increased mortality risk from cancer. No change in risk of mortality was found among men with ascorbate blood concentrations between 28.4 to 73.8 micromol/L. Loria found that the vitamin C intake corresponding to the higher risk of mortality in men was less than or equal to 60 mg per day. No link between mortality and ascorbate levels were found among women. (25)

 

Vitamin C intake and cancer mortality:

Carr and Frei recommended a higher vitamin C intake of 90-100 mg per day to avoid chronic diseases after reviewing cohort studies. They found that low intake of vitamin C was related to an increase in cancer mortality. They also had a different conclusion than Loria et al in that intake of vitamin C was inversely related to cancer mortality in elderly women but not mortality in men. (50)

An analysis, was conducted on 19,496 men and women, ages 45 to 79, in the U.K. The participants’ blood was tested for ascorbic acid (a form of vitamin C) and they were placed in five groups (quintiles) according to their serum ascorbic acid levels. Men and women were tracked separately. The researchers observed deaths from cancer and all causes in each of the blood ascorbic acid quintiles. In every case (except for women at risk of cancer), death rates were significantly lower among those with higher blood ascorbic acid levels. People with the highest ascorbic acid levels had half the risk of dying from all causes combined. Additionally, a 20 micromol/L increase in blood ascorbic acid concentration, the same as a 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality. (26)

Vitamin C has been shown to be beneficial for people with certain diseases or conditions. High intakes of vitamin C have been associated with decreased risk of heart disease, cancer, eye diseases, and neurological conditions. High dose vitamin C, with an upper tolerable level set at 2 grams per day set by the USDA has been shown to be safe. This limit was set by the USDA due to gastrointestinal side effects. Among healthy individuals, the recommended daily intake of vitamin C is 75 mg for women and 90 mg for men. (27)

 

Combinations of vitamins, minerals, and cancer:

Ten-year follow-up results from the General Population Trial, a study conducted in in Linxian, China from 1985 to 1991 that gave daily vitamin and mineral supplements (50 microg selenium, 30 mg vitamin E, and 15 mg beta-carotene) to 29,584 adults at high risk of esophageal and stomach cancers were presented. In the original study, researchers had found that treatment led to a decrease in mortality from all causes, cancer overall, and gastric cancer. Adding to these important findings, post-intervention follow-up indicated that the beneficial effects of the beta-carotene–vitamin E–selenium combination in the General Population Trial remained evident up to 10 years after the intervention. Cumulative mortality decreased from 33.62% to 32.19% and cumulative gastric cancer mortality decreased from 4.28% to 3.84%. These benefits were consistently greater in participants who were younger (<55 y) at the beginning of the intervention. (28)

 

Selenium and cancer:

A multicenter, double-blind, randomized, placebo-controlled trial of 1,312 patients with a history of basal cell cancers (BCC) or squamous cell cancers (SCC) and a mean follow-up of 6.4 years showed that 200 mcg of selenium failed to decrease the development of skin cancer and may increase the risk of BCC (by 10%) and SCC (by 14%) compared to placebo. However, the results also indicated that with supplementation, total cancer incidence was decreased by 37% (77 in the selenium group compared to 119 in the control group), total cancer mortality was decreased 50% (29 in the selenium group compared to 59 in the placebo group), and prostate cancer incidence was decreased by approximately 50% compared to placebo. There was also a lower incidence seen in lung and colorectal cancers but this finding was not statistically significant. (29)

 

Nutrition, foods and diet related to cancer:

Red meat consumption and cancer:

Red meat consumption has been found to be associated with various forms of cancer in a multisite case-control study of 11 cancer sites in Uruguay. High consumption of red meat was associated with an increased cancer risk of the oral cavity and pharynx (odds ratio [OR]= 3.65), esophagus (OR= 3.36), larynx (OR=2.91), stomach (OR= 2.19), colorectum (OR= 3.83), lung (OR= 2.17), breast (OR= 1.97), prostate (OR= 1.87), bladder (OR= 2.11) and kidney (OR= 2.72). Lamb was also associated with increased cancer risk. Eating a lot of processed meat was also linked to an increased risk of cancers of the esophagus (OR= 1.63), larynx (OR= 1.84), stomach (OR= 1.62), colorectum (OR= 2.15), lung (OR= 1.70) and breast (OR= 1.53). (30)

It has long been suspected that red meat contributed to cancer risk in patients.  According to a study conducted between 1983 and 1996 on patients with a red meat intake of at least 7 times per week, the incidence of cancers of the stomach, colon, rectum, pancreas, bladder, breast, endometrium, and ovaries was higher.  Therefore, it suggested that the reduction of red meat in the diet might lower the risk factors for these types of cancers.  Of note, cancer of the oral cavity, pharynx, esophagus, liver, gallbladder, larynx, kidney, thyroid, prostate, Hodgkin’s disease, non-Hodgkin’s lymphomas and multiple myeloma were not found to be associated with meat intake.  Of note, the study found that there was no reduction in risk of any of the cancers mentioned above with meat intake. (31)

 

Vegetarian diet and cancer:

A meta-analysis by Huang T et al consisting of 7 studies with a total of 124,706 participants from the UK, Germany, USA, Netherlands and Japan investigated cancer incidence among vegetarians and non-vegetarians. All-cause mortality in vegetarians was found to be lower when compared to non-vegetarians. Researchers also found a statistically reduced rate for vegetarians in terms of cancer incidence of 18%. This study suggests vegetarians have a mortality advantage compared to non-vegetarians. (32)

A 12-year study investigated the relationship between diet and risk of certain cancers. Researchers followed 61,566 British men and women, which included 32,403 meat eaters, 8,562 non-meat eaters who ate fish but not meat (the “fish eaters”) and 20,601 vegetarians (ate neither fish nor meat). Over the follow-up period there were 3,350 incident cancers, including 2,204 among the meat eaters, 317 among the fish eaters and 829 among the vegetarians. In this study, cancer among meat eaters was 3.8%, among fish-eaters, 0.5%, and among vegetarians, 1.3%. The study found that compared to meat-eaters, vegetarians had a 53%, 45% and 74% reduced risk in bladder, leukemia/lymphoma, and stomach cancers, respectively. Looking at all cancers combined, vegetarians were 12 per cent less likely to develop cancer than meat eaters, while fish eaters were 18 per cent less likely to develop cancer. (33)

 

Fruits, vegetables, and cancer risk:

Carotenoid intake and cancer:

According to a large prospective study of 83,234 women (aged 33-60 years old), consumption of foods rich in specific carotenoids (plant pigments found in carrots, sweet potatoes, spinach, kale, collard greens, papaya, bell peppers, tomatoes) and vitamins A, C, and E may reduce the risk of breast cancer among premenopausal women. Increased intake of lutein and zeaxanthin (both carotenoids), and vitamin A supplements, as well as beta-carotene from food were found to lower the risk of breast cancer in premenopausal women, but the link was found to be weak. However among women with a family history of breast cancer, this association was strong. Researchers reported that higher intake of beta-carotene was associated with a moderately reduced risk of breast cancer among women consuming 15 g/d of alcohol or more. Furthermore, premenopausal women eating at least 5 servings of fruits and vegetables per day had a significant reduction of breast cancer risk compared to women who had less than 2 servings per day. Premenopausal women with a family history of breast cancer who consumed more than 5 servings of fruits and vegetables per day received the greatest benefit from carotenoids with a moderately reduced risk of breast cancer. (34)

 

Fruit, vegetables, and cancer risk:

A study which looked at the relationship between intake of vegetables and fruit and its effect on the risk of cancer. A literature review of 206 human studies and 22 animal studies was conducted. Results of the literature review show that a high consumption of fruits and vegetables is associated with a decreased risk of human cancer at a number of common sites including stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit found to be most protective against cancer are raw vegetables, followed by allium vegetables (onion, garlic), carrots, green vegetables, cruciferous vegetables (broccoli, cauliflower, Brussels sprouts, kale, cabbage), and tomatoes. The recommendation is to increase fruit and vegetable consumption in general (e.g., “five a day”). (35)

A meta-analysis was done of multiple case-control and cohort studies looking at intake of fruits or vegetables and compared this to cancer risk. Researchers analyzed studies between 1973 and 2001. A large number of studies assessed the results for different cancer sites individually. There was a significant reduction in risk for esophageal, lung, stomach and colorectal cancers found with both fruit and vegetable consumption. There was a reduced risk of bladder cancer seen with fruit consumption but not vegetables. The estimates of relative risk from the cohort studies suggested a protective effect of fruits and vegetables for many types of cancers. (37)

 

Cruciferous vegetables and cancer:

An extensive review of epidemiological studies published prior to 1996 reported that the majority (67%) of 87 case-control studies found an inverse association between some type of brassica vegetable intake (including cabbage, kale, broccoli, Brussels sprouts, and cauliflower) and cancer risk at various sites. For cabbage, broccoli, cauliflower, and Brussels sprouts, these percentages were 70, 56, 67, and 29%, respectively. The results of 7 cohort studies also showed an inverse relationship between brassica consumption and risk of cancer. The higher the consumption of brassica vegetables the lower the risk of cancer. The inverse association appeared to be most consistent for cancers of the lung and digestive tract and least consistent for prostatic, endometrial, and ovarian cancer. In summary, a high consumption of brassica vegetables is associated with a decreased risk of cancer. (36)

 

Fruits, vegetables and renal cancer:

Eating fruits and vegetables was linked with a reduced risk of kidney cancer (RCC, renal cell carcinoma) in men (n=116), but not women (n=132). Men who consumed at least 6 servings of fruits and vegetables per day had a 55% reduced risk of RCC compared to men who had less than 3 servings per day. Vitamin A and C was found to be inversely associated with RCC in men. Vitamin E had no clear link to RCC in either men or women. (38)

 

Lignan intake and cancer:

A study by McCann SE et al evaluated the association between dietary lignin intake and survival. Lignans are antioxidants and phytoestrogens (chemicals that can act like hormone estrogen) found in a variety of plants, which includes flax seeds, pumpkin seeds, rye, soybeans, broccoli and some berries. Flax seed have the highest amount of lignans available from common nutritional sources. The data used in this study came from 1,122 women diagnosed with breast cancer between 1996 and 2001. Diet in the 12-24 months before diagnosis was assessed. For the women enrolled in this study, the main food sources of lignans were dark bread, peaches, coffee, broccoli and winter squash. Researchers estimated the average lignan intake among the women to be 244 mcg/day. They also found a 51% reduction in all-cause mortality in those consuming higher lignan levels (the lowest risk of dying was seen in women consuming >318 mcg per day). These same women were far less likely to die of breast cancer. They had a 71% decreased risk of dying of breast cancer. The intake of dried beans was also associated with a 39% reduced risk of all-cause mortality. (39)

 

Aspirin use for the prevention of cancer:

Frequency of aspirin use and cancer risk: In a study by Bardia A et al, regular aspirin use was associated with a lower cancer incidence and cancer mortality, but non-aspirin non-steroidal anti-inflammatory drug (NSAID) use was not. The beneficial effects of aspirin were stronger in former and never smokers than current smokers. Among 22,507 cancer-free postmenopausal women age 55-69 who provided information on aspirin and NSAID use, those who said they regularly used aspirin had a 16% reduced risk of developing cancer more than a decade later. There was also a 13% reduced risk of dying from cancer over this same time period, compared to women who did not use aspirin. Aspirin use decreased the risk of mortality from coronary artery disease by 25% and reduced the risk of all-cause mortality by 18%. Ever use of aspirin was associated with a lower risk of cancer than those women who never used aspirin. Aspirin use greater than 6 times per week was compared to aspirin use 2-5 times per week, over 1 time per week, ever use , and never use. The higher the frequency of aspirin use, the lower the incidence of cancer. Also the higher the frequency of aspirin use, the lower the cancer mortality. The women with the lowest all-cause mortality took aspirin 2-5 times per week. There was no statistically significant impact on cancer incidence or mortality among women who used non-aspirin NSAIDs, compared to those who did not. (40)

 

The U.S. Preventive Services Task Force (USPSTF) statement on use of aspirin for prevention of colorectal cancer:

To prevent colorectal cancer in individuals at average risk for colorectal cancer the U.S. Preventive Services Task Force (USPSTF) recommends against the routing use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). According to the USPSTF, aspirin is required in higher doses than cardiovascular and ischemic stroke prevention. The higher doses of aspirin and NSAIDs required to prevent polyps and colorectal cancer poses a risk of severe bleeding episodes. Therefore, the USPSTF has determined that the risk of hemorrhagic stroke with aspirin outweighs the benefit of colorectal cancer prevention. The risk of gastrointestinal bleeding and hemorrhage with NSAIDs outweigh the benefits of colorectal cancer prevention. (41)

The USPSTF recommends against aspirin for prevention of colorectal cancer because it requires higher doses in order to accomplish this, however, if aspirin is recommended for cardiovascular disease or stroke prevention, there may be benefit obtained by aspirin in the prevention of cancer. According to a study by Bardia A et al mentioned above, cancer incidence and cancer mortality was reduced even in patients that used aspirin infrequently compared to those that never used it. (42)

 

Whey protein and cancer:

A low glutathione (GSH) concentration has been shown in research to be associated with an increase in risk of cancer. Whey proteins have been shown to increase GSH concentration which may prevent the development of several types of tumors. Bounous G et al suggested that whey protein antitumor activity results from an increase in GSH concentration. (43)

A specially prepared whey protein supplement, Immunocal, has been shown to reduce glutathione (GSH) concentration (which at high levels has been linked to tumour cells) and inhibition of growth in human breast cancer cells. In this 6 month study, 5 patients with metastatic carcinoma of the breast, 1 of the pancreas and 1 of the liver were administered 30 grams of Immunocal daily. In 6 patients GSH levels were high at the start of the study. In 2 patients tumor regression, normalization of hemoglobin, peripheral lymphocyte counts and a sustained drop of lymphocyte GSH levels towards normal were reported. Another 2 patients showed signs of tumour stabilization and increased hemoglobin levels. In 3 patients there was disease progression with a trend toward higher GSH levels. These findings suggest that whey protein may reduce the concentration of GSH in tumour cells. (44)

 

Obesity, body mass index, and cancer:

A prospective study of a large participant pool of 404,576 men and 495,477 women examined the association between body mass index and the risk of death from cancer at specific sites. After 16 years of follow-up, there were 32,303 deaths from cancer in men and 24,842 deaths from cancer in women.  For most individual cancer sites, there was an association between body mass index and mortality. There was a positive linear trend in death rates with increasing body mass index for all cancers. Men in the highest body mass index group (>40) were 52% more likely to die of all cancers than men in the lowest body mass index group (18.8 – 24.9). For women the risk was even greater, at 62%. The conclusion of the study was that the proportion of all deaths from cancer attributable to overweight and obesity in U.S adults over 49 years old may be a high as 14% for men and 20% for women. The author stressed that more than 90,000 deaths per year from cancer might be avoided if everyone in the adult population could maintain a body mass index under 25 throughout life. (45)

 

Agaritine and cancer risk:

Agaritine consumption in fresh mushrooms may carry a small cancer risk. More research is needed, however mushrooms may be cooked prior to eating which removes agaritine and eliminates the possible risk.

Agaritine is a naturally compound found in mushrooms. According to research of toxicity of agaritine in transgenic mice, an estimated human consumption of 4 g/day of Swiss mushroom would be expected to contribute a lifetime cumulative cancer risk of about 2 cases per 100,000 lives. For 15 weeks, female mice were given one of 3 diets: fresh mushrooms 3 days/week followed by normal lab chow for 4 days/week (averaged daily agaritine dose 30mg/kg) or 80 mg/kg daily freeze-dried mushrooms mixed at 25% agaritine or 120 mg/kg daily of mushroom extract containing 30% agaritine . (46)

Agaritine is a naturally compound found in mushrooms. Agaritine has been described in some studies as potentially harmful agent which may lead to cancer, however, studies using mushrooms and mushroom extracts have not provided significant evidence of the harmful effects of agaritine or mushroom consumption. (47)

 

Indian gooseberry and tumor cells:

Scientists tested the anti-cancer effects of phyllanthus emblica (PE), Indian gooseberry known for its medicinal properties. In a series of experiments on mice and on human cancer cell lines, they found that an extract of PE may help slow tumor growth and promote apoptosis (a type of programmed cell death essential for stopping the proliferation of cancer cells). PE extract at 50-100 mcg/mL significantly inhibited cell growth of six human cancer cell lines: lung, liver, cervical, breast, ovarian and colorectal. Additionally, researchers saw a 50% reduction of tumor numbers and volumes in mice treated with PE extract. PE extract at 25 and 50 micrograms/mL was also shown to inhibit invasiveness of breast cancer cells. These results suggest PE has anti-cancer properties against certain cancer cells. (48)

 

 

Assessment and Plan: Cancer Prevention Possibilities

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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