Lower Cancer Rates Research Articles

Dietary Antioxidants and Cardiovascular Disease

Publisher Summary This chapter summarizes the basic science behind the hypothesis that antioxidants that might prevent cardiovascular disease (CVD). It reviews the observational epidemiology that relates to this hypothesis, and discusses the results of randomized trials examining primary and secondary prevention of CVD through dietary supplementation. The risks and benefits of various aspects of diet are likely to accrue over years or even decades, and eating habits change over time. Studies of diet and chronic disease may have to continue for many years and be updated periodically. Quantitative assessment of diet is based on self-reports, which results in misclassification. Dietary habits tend to be imbedded in cultural practices and associated with lifestyle factors, making it difficult to separate the effects of diet from other related factors on a given disease. One of the most consistent findings in dietary research is that those who consume higher amounts of fruits and vegetables have lower rates of cancer, heart disease, and stroke. Possible explanations for these apparent protective effects include higher dietary fiber intake, the replacement of fats and cholesterol, or specific micronutrients in fruits and vegetables, particularly those with antioxidant properties.

Worldwide Variations in the Lifetime Probability of Reproductive Cancer in Women

Abstract Cancer incidence in countries representative of three patterns of reproductive cancer and age-specific mortality was used to estimate the effect of oral contraceptive use on the lifetime probability of reproductive cancer under three sets of assumptions about the effects of oral contraceptives. Under the set of assumptions considered likely, oral contraceptives were estimated to reduce or increase only slightly the lifetime probability of any reproductive cancer in each setting. Under worst-case assumptions, oral contraceptives were estimated to increase the lifetime probability of reproductive cancer only modestly in settings with low cancer rates and in settings with high rates of breast, ovarian, and endometrial cancer, but it might have a large impact on lifetime probability of reproductive cancer in settings with high cervical cancer rates. Under best-case assumptions, oral contraceptives were estimated to decrease the lifetime probability of reproductive cancer in each setting; this reduction was estimated to be greatest in settings where endometrial and ovarian cancer incidence are high.

Nitrate and N-nitrosoproline excretion in two Italian regions with contrasting rates of gastric cancer: the role of nitrate and other factors in endogenous nitrosation.

Exposure to nitrate and propensity for endogenous nitrosation were examined in 80 healthy males, aged 25-40 years, residing in areas of Italy with long-standing high (Florence) and low (Cagliari) rates of gastric cancer. Nitrate exposure was assessed by measurement of urinary nitrate excretion over 12 hr, and endogenous nitrosation was assessed using the N-nitrosoproline test (NPRO-test). Our hypothesis was whether the geographic variation in cancer rate correlated with nitrate exposure or nitrosating ability. Exposure to background sources of NPRO was significantly higher in the high-risk subjects (phi = 0.04) whereas no differences were found in exposure to nitrate or in urinary NPRO levels after L-proline loading (test NPRO levels). The regional difference in test NPRO was almost completely accounted for by background NPRO exposure. Examination of individual rather than grouped data revealed that exposure to nitrate was a major factor in NPRO formation. No other factors studied (age, dietary-questionnaire-assessed intake of anti-oxidant vitamins) had a significant effect. Geographical variation in gastric cancer risk did not, therefore, correlate with either nitrate exposure or propensity for endogenous nitrosation of L-proline.

Worldwide variations in the lifetime probability of reproductive cancer in women: Implications of best-case, worst-case, and likely-case assumptions about the effect of oral contraceptive use

Cancer incidence in countries representative of three patterns of reproductive cancer and age-specific mortality was used to estimate the effect of oral contraceptive use on the lifetime probability of reproductive cancer under three sets of assumptions about the effects of oral contraceptives. Under the set of assumptions considered likely, oral contraceptives were estimated to reduce or increase only slightly the lifetime probability of any reproductive cancer in each setting. Under worst-case assumptions, oral contraceptives were estimated to increase the lifetime probability of reproductive cancer only modestly in settings with low cancer rates and in settings with high rates of breast, ovarian, and endometrial cancer, but it might have a large impact on lifetime probability of reproductive cancer in settings with high cervical cancer rates. Under best-case assumptions, oral contraceptives were estimated to decrease the lifetime probability of reproductive cancer in each setting; this reduction was estimated to be greatest in settings where endometrial and ovarian cancer incidence are high.

Fusarium moniliformeand Fumonisins in Corn in Relation to Human Esophageal Cancer in Transkei

Homegrown corn samples were collected from areas with high and low rates of human esophageal cancer in the southern African territory of Transkei for six seasons over the period of 1976-1989. The most consistent difference in the mycoflora of the corn kernels was the significantly higher incidence of Fusarium moniliforme in corn from high-vs. low-rate areas. In the 1989 samples, this significant (P<0.01) difference in high- and low-rate cancer areas was 41.2 and 8.9%, respectively, in good (visibly nonmoldy) corn and 61.7 and 21.4%, respectively (...)

Detection of HPV DNA in neoplastic and non‐neoplastic cervical specimens from pakistan and japan by non‐isotopic in situ hybridization

In order to determine the prevalence and type-specific distribution of human papillomavirus (HPV) in women from Pakistan, a country with a low cervical cancer rate (hospital-based data), and to compare these results with their counter-parts in Japan, we studied 56 non-neoplastic cervical tissues and 162 cervical carcinoma cases from both countries. HPV infection was defined by in situ hybridization in paraffin-embedded tissues using biotinylated HPV 6/11, 16 and 18 probes. The overall positivity rates in non-neoplastic and neoplastic cervical tissues from Pakistan were 33% and 88%, while in those from Japan the rates were 46% and 80%, respectively. High-risk HPVs (16 & 18) were found in 17% of the non-neoplastic specimens and in 69% of cervical carcinoma cases from Pakistan, while Japanese figures in this respect were 19% and 68%, respectively. No correlation was found between the type-specific distribution or prevalence of HPV and the geographic location of the cases examined in the 2 countries. However, in comparison to Japanese women, the incidence of HPV-16-positive cervical carcinoma in Pakistani women decreased significantly (p less than 0.05) in the oldest age group as compared to the youngest age group.

Comparisons of Diet and Biochemical Characteristics of stool and Urine Between Chinese Populations With Low and High Colorectal Cancer Rates

In an investigation of the roles of diet and stool biochemistry in human colorectal carcinogenesis, 24-hour food, urine, and stool samples were collected from randomly selected participants from two populations with a fourfold difference in colorectal cancer risk: Chinese in Sha Giao, People's Republic of China (low risk), and Chinese-Americans of similar ages in San Francisco County, Calif, in the United States (high risk). The findings supported the hypotheses that colorectal cancer risk is increased by the consumption of high-fat, high-protein, and low-carbohydrate diets and is associated with high levels of cholesterol in stool as well as increased daily outputs of 3-methyl-histidine and malonaldehyde in urine. However, risk does not increase with low stool bulk and low total stool fibers.

Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan

Serum oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG) levels were studied in postmenopausal Japanese women in Japan (n = 91) and postmenopausal American white women (n = 38). The Japanese women were deliberately chosen to be from a rural agricultural area in order to get samples which represent as closely as possible the traditional Japanese 'lifestyle' that gave rise to the low rates of breast cancer in Japan. E1 levels were 47%, and E2 levels 36%, greater in the American women; these differences were only reduced to 43% and 27% after adjustment for the lower weight of the Japanese. These results were all statistically highly significant. There was little difference in SHBG levels between the Japanese and the American women. These results for E1 and E2 could be an important part of the explanation why Japanese and American breast cancer rates continue to diverge further after the menopause.

Cervix and breast cancer incidence in immigrant Caribbean women.

Cervix and breast cancer incidence in 1978-82 was computed for immigrant and United States-born Black women in Brooklyn, New York. Compared to the national SEER (Surveillance, Epidemiology and End Results) rates, US-born and Haitian women had high rates of invasive cervical cancer, while English-speaking Caribbean immigrants had an average rate. However, while US-born women had an average rate of carcinoma in situ of the cervix, both immigrant groups had low rates. Both immigrant groups had low rates of breast cancer, whereas US-born Black women had an average rate.

Expected indoor 222Rn levels in counties with very high and very low lung cancer rates.

Counties in the U.S. with high lung cancer rates should have higher average 222Rn levels than counties with low lung cancer rates, assuming the average 222Rn level in a county is not correlated with other factors that cause lung cancer. The magnitude of this effect was calculated, using the absolute risk model, the relative risk model, and an intermediate model, for females who died in 1950-1969. The results were similar for all three models. We concluded that, ignoring migration, the average Rn level in the highest lung cancer counties should be about three times higher than in the lowest lung cancer counties according to the theory. Preliminary data are presented indicating that the situation is quite the opposite: The average Rn level in the highest lung cancer counties was only about one-half that in the lowest lung cancer counties.

MARRIAGE ASSOCIATED WITH BETTER CANCER PROGNOSIS.

Previous reports have shown that married people live longer and have lower cancer rates. Goodwin and colleagues report data suggesting that being married is associated …

The relationship between breast cancer and augmentation mammaplasty: an epidemiologic study.

Surgical implantation of breast prostheses for cosmetic purposes has become increasingly popular, and by 1981, it was estimated that three-quarters of a million women had had such an operation. The long-term potential risks, particularly of breast cancer, of such procedures have not been properly investigated. To evaluate the potential breast cancer risk, we have conducted a retrospective cohort study of 3111 women followed through various public and medical records for a total of 18,476 person-years, with a median of 6.2 years per person. The cases of breast cancer were detected by means of a computerized match with the Los Angeles County Cancer Surveillance Program, a population-based cancer registry. Overall, 15.7 breast cancer cases were expected and 9 were observed, a nonsignificant deficit [standardized incidence ratio (SIR) = 57 percent, 95 percent confidence limits: 26 percent, 109 percent]. The cancers were generally diagnosed at an early stage. Among the 573 women aged 40 or older at implantation, 7.1 cases were expected and 8 were observed (SIR = 113 percent). In women whose implants were performed before the age of 40, only 1 case was observed whereas 8.6 cases were expected (SIR = 12 percent, 95 percent confidence limits: 0.3 percent, 65 percent), a significant difference. These data do not support an increased risk of breast cancer following augmentation mammaplasty. The low breast cancer rate in women having augmentation mammaplasty at a young age that many such women may have a reduced amount of breast tissue, but data on this are unavailable.

Guidelines and an illustration of the use of ecological data for seeking clues of excess risk

Ecological studies have acquired a bad reputation as weak scientific studies suffering from the ecological fallacy and many intractable limitations of data and method. In order to reduce these problems, it is suggested that analyses be focused on specific populations-at-risk, diseases, risk factors and places. In addition, seven guidelines are suggested which will limit the possibility of false positive results and provide the best clues for expensive, follow-up research. These guidelines are testing to make sure that the results are consistent across different times, places and methods. The guidelines were applied to finding the best clues for occupational-related cancers among white males aged 35–64 in the State of Illinois during 1950–1975. The most interesting clue found was that most coal mining areas in Illinois during the late 1960s and 1970s manifested the highest cancer mortality rates of trachea, bronchus, and lung and among the highest rates of increase of this type of cancer. This finding was unexpected because many studies have shown low lung cancer rates among coal miners.

Cancer in Utah Mormon men by lay priesthood level.

Mormons have been shown to have low cancer rates at several common sites, particularly those associated with tobacco and alcohol use. This likely reflects adherence to their Church doctrines advocating abstention from the use of these substances. All Mormons, however, do not adhere to the health practices of their Church, and this study classifies Utah Mormon men by their lay priesthood offices, which reflect degree of adherence to Church doctrines. Follow-up cancer rates for 1966-1970 indicate that the most devout group (Seventies and High Priests) have lung cancer rates 80% lower than those of the least devout group. The same was seen for all smoking- and alcohol-associated cancer sites combined. Cancer of the stomach and the leukemias and lymphomas also had lower rates in the most devout group. Cancers of the colon-rectum, prostate, and pancreas showed little difference in rates when classified by lay priesthood office. These data provide a demonstration of the effects of a healthy lifestyle on cancer occurrence in men.

Cancer in Utah Mormon women by church activity level.

In light of low cancer rates by the Mormon Church, this study classifies female Mormon cancer patients in Utah according to measures of adherence to Church doctrines. The distribution by Church activity level is compared for each site to a group of other cancer sites felt to represent the overall activity level distribution of Utah Mormon women. Mormon women classified as having the strongest adherence to Church doctrines had lung cancer rates during 1966-1970 much lower than did women with the weakest adherence. The relationship was not as strong, however, as that seen in Mormon men when classified by lay priesthood office. Cancer of the uterine cervix also showed lower rates in the more active groups, but this finding was not statistically significant. Cancers of the breast and ovary did not show consistent associations with Church activity level, nor did most of the gastrointestinal cancers. These data suggest that some of the differences in cancer incidence between Mormons and non-Mormons may not be explained by adherence to specific Church doctrines.

Case definition in case-control studies of the efficacy of screening.

Evaluation of the efficacy of screening programs involves the comparison of morbidity or mortality rates between screened and unscreened populations. Such comparisons are made most convincingly by means of experiments (1, 2), exemplified by the study of screening for breast cancer carried out by the Health Insurance Plan of Greater New York (HIP) (3). However, there are serious practical difficulties with experimental studies of screening: they are expensive, may require many years to complete, and usually can be done only when new screening procedures are introduced. Once a procedure is established as a part of medical practice, as the Papanicolaou (Pap) smear is, it may be necessary to rely on nonexperimental methods to evaluate it. Nonexperimental studies are more susceptible than are experimental ones to confounding. For example, social class (as reflected in education or income) is directly related to frequency of screening with the Pap smear, but is inversely related to cervical cancer rates; relatively low rates of cervical cancer among frequently screened women could be secondary to their relatively high social class. Despite this drawback of the nonexperimental approach, there may be times when it will be able to provide information that cannot be obtained otherwise. (A discussion of the roles of experi-

The dietary intake of Laminaria, a brown seaweed, and breast cancer prevention.

Based on epidemiological and biological data, Laminaria, a brown kelp seaweed, is proposed as an important factor contributing to the relatively low breast cancer rates reported in Japan. Several possible mechanisms for the influence of Laminaria on breast cancer are proposed: Laminaria is a source of nondigestible fiber, thereby increasing fecal bulk and decreasing bowel transit time; it changes the posthepatic metabolism of sterols; it contains an antibiotic substance that may influence fecal ecology; it contains 1-3 beta glucan, which alters enzymatic activity of fecal flora; and it stimulates the host-mediated immune response. It is suggested that Laminaria may play a role in preventing either the initiation of breast cancer or its promotion by endogenous physiological factors.

Epidemiologic and Dietary Evidence for a Specific Nutritional Predisposition to Esophageal Cancer

A total of 21 different regions were found to have a very low relative frequency and/or low incidence rates of esophageal cancer (the male mean being 0.6 and the range being 0.1--1.0/100,000 per annum). In all these areas the dietary staples were either sorghum, millet, cassava, yams, or peanuts or a combination of these items. In another 17 areas that had a high risk for esophageal cancer (the male mean being 41.3 ad the range being 16.5--86.0/100,000 per annum), the dietary staple was invariably corn or wheat. It is calculated that dietary staples associated with a high risk for esophageal cancer will be marginal or deficient particularly in riboflavin, nicotinic acid, magnesium, and zinc, whereas dietary staples associated with a low risk for esophageal cancer will be rick in these substances. the evidence presented supports the concept that these high rates of esophageal cancer in diverse peoples are associated with long-standing deficiencies of a few micronutrients and explains epidemiologic features such as geographic variation, recent emergence of the disease in Africa, and the role of alcohol abuse.

Urine estrogen profiles in European countries with high or low breast cancer rates

Urine estrogens of women in two age groups, 15–18 and 30–39, were measured in four northern European countries where breast cancer rates are high, two southern European countries where they are low, and in Finland, a northern country where incidence rates are comparable to those of the southern countries and mortality rates are intermediate. The estriol ratio (the ratio of the concentration of estriol to the sum of those of estrone and estradiol) was lower in the high-risk countries than in the low-risk areas in both age-groups and in both the follicular and luteal phases of the menstrual cycle. In two of the four comparisons the difference was statistically significant. This provides modest support to the hypothesis that a population's breast cancer risk is inversely related to the estriol ratios of its young women. However, the data from Finland are not consistent with this hypothesis, the Finnish women having lower mean estriol ratios than the women in the high-risk areas. The pregnanediol levels of the young Finnish women were also unusually low, suggesting a high frequency of anovulatory menstrual cycles.

Pernicious anaemia as a risk factor in gastric cancer.

In order to assess the risk of gastric cancer (GC) developing in patients with pernicious anaemia (PA), the prevalence of PA was analysed in all patients with GC notified to the Danish Cancer Registry in 1972. Among 877 patients with GC, PA had previously been diagnosed in 19 (2.2%). In seven of these, PA had been diagnosed only shortly before GC. Accordingly, the diagnosis of PA could be regarded as unquestionable only in the remaining 12 cases (1.3%). In either case, the frequency of PA was significantly higher than in a reference group of patients with cancer of the colon who had been selected in the same way. Calculation of the incidence of GC in PA patients showed that this was about three times higher than in the general population. The annual risk of GC was calculated to be 0.3%. In PA patients, the tumour was primarily localized to the body and fundus of the stomach, whereas it mainly involved the antral and pyloric region in patients without PA. In view of the low cancer rate it is concluded that routine gastroscopy and barium meal examination are not indicated in PA patients in general. Whenever a patient with PA complains of dyspepsia, examinations with gastroscopy and barium meal should, however, be carried out on liberal indications.