changes that accompany or lead to obesity also increase
the risk of developing cancer. Obese women are at greater
risk of endometrial, ovarian and possibly breast cancer,
while obese men have an increased risk of prostate
cancer. ( Garfinkel
L., Moller H.) The increased incidence of these
cancers among obese patients ist probably a direct
consequence of the hormonal changes already outlined.
Obese patients are also at increased risk of gastrointestinal cancers, such as colorectal and gallbladder cancer. (Austoker J.) Dietary factors that promote weight gain, such as a high dietary fat content, may give rise to the high incidence of gastrointestinal cancers in obese patients.Many factors influence the risk of developing cancer. In obese patients, the degree of obesity adds to other predisposing factors such as age and family history.
There is a sharp rise in the incidence of endometrial cancer as BMI climbs from 25 kg/mē (Levi F.) BMI, however, does not distinguish between central and lower body obesity. Studies have shown that central obesity further increases the risk of developing this cancer.
Abdominal biopsy studies have shown that the ratio of unsaturated to saturated fatty acids is altered in favor of unsaturated fatty acids in obese women with endometrial cancer. (Lissner L.) The fatty acid profile of the abdominal wall is highly correlated with the profile of the fats consumed. A diet high in saturated fat and low in fibre probably increases the risk of cancer. High energy intake may also increase the risk of gastrointestinal cancers.
The relationship between breast cancer and obesity, however, is less clear. Age has a significant impact on the risk of breast cancer, though post-menopausal obese women are at higher risk than post-menopausal lean women (Levi F.). Fat distribution also affects the risk of breast cancer; an increased risk of breast cancer is more highly correlated with central obesity than with BMI. (Ballard-Barbash R., Schapira D.V.).
CT scanning has been used to determine the ratio of subcutaneous fat to central fat in women with breast cancer. Compared with controls, the breast cancer patients had a significantly lower subcutaneous to central fat ratio. (Schapira D.V).
Family history also compounds the risk of breast cancer in obese patients. Women with a positive family history of breast cancer and central obesity are at the greatest risk of developing breast cancer (Ballard-Barbash R.).
The incidence of colorectal cancer shows a strong relationship with BMI. (Suadicani P.) Studies have shown that lean populations have a lower risk of gastrointestinal cancers than obese populations (Frentzel-Beyme R). It ist not known how obesity affects colorectal cancer rates. Current thinking, however, suggests that a lowfat diet and balanced nutrition could play an important role in reducing the risk of cancer in lean populations.
Ann Intern Med (United States), Dec 1985, 103(6 ( Pt 2)) p1034-6
In a prospective study, mortality ratios were computed in relation to overweight, cancer, and other diseases. The study included 750 000 men and women followed for 12 years. Each person was given a weight index. Death rates for overweight and underweight persons were compared with rates for persons of average weight. Men who were 40% or more overweight had a mortality ratio for cancer of 1.33; women, 1.55. This ratio was much lower than that for coronary heart disease (men, 1.95; and women, 2.07); diabetes (5.19 and 7.90), and digestive diseases (3.99 and 2.29). Overweight men had significantly higher mortality ratios for colorectal and prostate cancer; overweight women had much higher rates for cancer of the endometrium, gall bladder, and cervix; and also significantly higher rates for ovary and breast cancer.
Eur J Cancer (England), 1994, 30A(3) p344-50
Moller H; Mellemgaard A; Lindvig K; Olsen JH
A cohort of 43,965 obese persons was accrued on the basis of discharge registrations from Danish hospitals, and incidence of cancer in the cohort was compared to that in the Danish population as a whole using indirect standardisation for age and period. Increased incidence was observed for cancer of the uterine corpus independently of age [114 cases, relative risk (RR) = 2.0, confidence interval 1.6-2.4], and for breast cancer in women above the age of 70 (133 cases, RR = 1.2). These findings are consistent with previous studies. In younger women, breast cancer occurred less frequently and ovarian cancer occurred more frequently than expected. Increased incidence was observed for cancers of the oesophagus (26 cases, RR = 1.9) and the liver (58 cases, RR = 1.9), probably reflecting an increased prevalence of excessive alcohol consumption in the cohort. Increased incidence was furthermore observed for cancers of the pancreas (101 cases, RR = 1.7), the prostate (96 cases, RR = 1.3) and the colon (195 cases, RR = 1.2), which may indicate the existence of risk factors which are common to obesity and to these cancers, for example, dietary habits. Kidney cancer was increased in women only. Overall, the incidence of cancer was increased by 16% in the cohort. The results were essentially unchanged by restriction to the subcohort of 8207 persons in whom obesity was the primary discharge diagnosis, and were also similar in the first year of follow-up after hospital discharge. Selection bias is, therefore, not likely to have influenced the results.
BMJ (England), Jun 18 1994, 308(6944) p1610-4
Accumulating data indicate that modifications in diet may reduce the risk of cancer by as much as one third and possibly by as much as two thirds. On the basis of the existing evidence, however, it is not possible to be certain which cancers are causally related to diet and what proportion of them are due to specific components of the diet. Diet is currently thought to be a major factor in the aetiology of cancers of the large bowel and stomach, and it may also be important in the aetiology of several other cancers. With the exception of strong and consistent evidence of the protective effect of fruit and vegetables, practical dietary interventions that reduce the risk of cancer are difficult to formulate as, in general, the evidence is theoretical or contradictory and too weak to justify specific intervention. Authoritative guidelines on dietary management in primary care are conspicuously absent because of lack of research. The success of an individual based strategy will depend on adequate education, training, and support being made available to the relevant members of primary care teams.
Acta Obstet Gynecol Scand (Denmark), Aug 1993, 72(6) p481-7
Lissner L; Kroon UB; Bjorntorp P; Blosk S; Wilhelmsen L; Silverstolpe G
This study describes associations between early-stage endometrial cancer and type of dietary fat consumed, based on (i) adipose tissue fatty acid content (a biomarker for dietary fat) and (ii) self-reported frequencies of selected high-fat foods. Because obesity may be associated with high dietary fat intake as well as endometrial cancer, a secondary objective is to determine whether the observed dietary associations are statistically independent of body composition, assessed as percent body fat. To achieve these aims, we examined 20 cases of endometrial cancer in remission and 20 community controls, all aged 55-64. Abdominal adipose tissue biopsies from cases contained significantly higher concentrations of saturated fatty acids of intermediate chain length (C12-C16), lower ratios of polyunsaturated to saturated fatty acids (P:S ratio), and lower concentrations of C18 polyunsaturated as well as C18 saturated fatty acids. These differences were independent of degree of adiposity measured in a whole body 40K counter and several measurements of regional fat distribution. In addition, each subject's consumption of 20 high-fat items was reported by means of a semiquantitative food frequency questionnaire. Analysis of these data indicated that cases consumed more animal-derived fats, again independent of obesity. In particular, cases used more butter in cooking, ate more bacon, and drank more whole milk. Animal-derived fat intake displayed an inverse association both with the P:S ratio and the C18 polyunsaturated fatty acid content of adipose tissue, lending internal validity to the dietary data. These findings are consistent with the hypothesis that the type of dietary fat consumed may influence the occurrence of endometrial cancer.
Int J Cancer (United States), Feb 20 1992, 50(4) p567-71
Levi F; La Vecchia C; Negri E; Parazzini F; Franceschi S
The relationship between body mass index (BMI) at different ages and subsequent endometrial-cancer risk was investigated in a multicentre case-control study conducted between 1988 and 1991 in Vaud, Switzerland, and Northern Italy on 272 histologically confirmed incident cases of endometrial cancer and 571 controls admitted to hospital for acute, non-neoplastic conditions, unrelated to known or potential risk factors for endometrial cancer. The risk of endometrial cancer increased with increasing BMI in the 3rd decade of age (20 to 29 years), in the 5th decade (40 to 49 years) and in the 7th decade (60 to 69 years), although the risk estimates tended to be substantially higher at older ages: compared with women whose BMI (kg m-2) was less than 20, the relative risks (RR) were 1.8 for BMI greater than or equal to 25 at age 20 to 29, 2.7 for BMI greater than or equal to 30 at age 40 to 49 and 3.8 at age 60 to 69. All the trends in risk were significant, except that for BMI at age 25 after allowance for current BMI. When data were examined in separate strata of current BMI, among women of normal body mass at diagnosis no significant effect of past overweight was observed. In contrast, among subjects over-weight at diagnosis, there were significant direct relationships with BMI at ages 20 to 29 and 40 to 49. To reduce endometrial cancer risk, it is therefore important to avoid obesity in later middle and older age, and the benefit can be even greater for women who were overweight at younger age.
J Natl Cancer Inst (United States), Feb 21 1990, 82(4) p286-90
Ballard-Barbash R; Schatzkin A; Carter CL; Kannel WB; Kreger BE; D'Agostino RB; Splansky GL; Anderson KM; Helsel WE
We examined the relation between central body fat distribution and breast cancer in a prospective cohort of women who participated in the Framingham Study. At the baseline examination in 1948, a total of 2,201 women aged 30-62 years were analyzed. An index of central to peripheral body fat (the central adiposity ratio) was calculated from the sum of the trunkal skinfolds (chest, subscapular, and abdominal) divided by the sum of the extremity skinfolds (triceps and thigh). These skinfolds were measured at the fourth examination in 1954. The cohort was followed for up to 28 years and yielded 106 cases of breast cancer. When divided into quartiles based on the central adiposity ratio, only women in the fourth quartile (those with the highest central to peripheral body fat distribution) demonstrated an increased risk for breast cancer. The age- and adiposity-adjusted relative risk estimate for having an increased central adiposity ratio (fourth quartile) compared to lower central adiposity ratios was 1.8 (95% confidence interval, 1.2-2.6). Adjustment for potential confounders of height, parity, and education did not appreciably alter this estimate (1.7, 1.1-2.5). There was no association between degree of adiposity, as measured by the sum of the five skinfolds or by body mass index (weight in kg divided by height in m2), and subsequent breast cancer. The results of this study suggest that increased central to peripheral body fat distribution predicts breast cancer risk independently of the degree of adiposity and may be a more specific marker of a premalignant hormonal pattern than degree of adiposity.
Cancer (United States), Jul 15 1994, 74(2) p632-9
Schapira DV; Clark RA; Wolff PA; Jarrett AR; Kumar NB; Aziz NM
BACKGROUND. The risk for breast cancer and the sex hormone abnormalities noted in breast cancer patients have been demonstrated in women with upper body fat obesity. The objective of this study was to determine if the visceral component of upper body fat obesity was correlated with breast cancer risk.
METHODS. A case-control study of 40 consecutively enrolled women with breast cancer and 40 community-based age, weight, and waist circumference-matched control subjects was conducted. The areas of visceral fat, subcutaneous fat, and total fat were measured using computed tomography at the L-4 vertebral body. Calculations of relative risk for breast cancer were based on these fat compartments.
RESULTS. Patients with breast cancer had a significantly greater visceral fat area (P = 0.01), visceral-to-total-fat area ratio (VT ratio) (P 0.001) and significantly lower subcutaneous-to-visceral-fat area ratio (SV ratio) (P 0.001) compared with the matched controls. The relative risk for breast cancer increased with increasing VT ratio ( or = 0.24 = 1.0; 0.24 = 9.5) (P 0.0001) and decreasing SV ratio ( or = 3.64 = 1.0; 3.64 = 8.5) (P = 0.0002).
CONCLUSIONS. Visceral obesity, as assessed by computed tomography, was a significant risk factor for breast cancer in women matched for age, weight, and waist circumference. Comparing the VT ratio for both groups, breast cancer patients had 45% more visceral fat compared with matched control subjects.
Cancer (United States), Aug 1 1994, 74(3 Suppl) p1090-100
Body size is one of the few breast cancer risk factors that can be modified throughout life and therefore should be considered in research on breast cancer prevention. The contrasting effects of body size on premenopausal breast cancer compared with postmenopausal breast cancer and the lack of a strong association between body mass and postmenopausal breast cancer in some cohort studies has led to a view that obesity has little influence on breast cancer risk. These conclusions are based on analyses that consider relative weight at one point in time as an adequate measure of lifelong weight patterns and their metabolic consequences. Recent research suggests that, compared to body mass indices, adult weight gain and increased central body fat may be more specific markers of the metabolic consequences of obesity and therefore may predict health outcomes more consistently. Adult weight gain and increases in central body fat, which commonly occur during menopause, have been associated consistently with an increased risk of postmenopausal breast cancer. The timing of weight gain also appears to influence breast cancer risk; increased relative weight and weight gain after menopause have been associated with the largest increases in relative risks. Overall levels of adiposity, increased central fat deposition, and weight gain are associated with alterations in ovarian hormone and glucose metabolism and in growth factors that may promote breast cancer cell growth. Data on lifelong weight changes and the location of fat depots may more precisely identify women with high risk patterns of sex steroid and glucose metabolism. Similarly, research is needed to determine if weight gain during periods of hormonal change, such as menarche, pregnancy, and menopause, have different biologic effects, perhaps because of differences in the location of fat deposition during these periods. Research also is needed on whether there are critical times relative to breast cancer promotion when excessive weight gain should be avoided. Data are lacking on the influence of weight loss or avoidance of weight gain on breast cancer risk or prognosis.
Scand J Gastroenterol (Norway), Mar 1993, 28(3) p285-8
Suadicani P; Hein HO; Gyntelberg F
The role of obesity in the risk of colorectal cancer is uncertain. We investigated the association between height and weight and the risk of colorectal cancer in an 18-year follow-up of 5249 employed men aged 40-59 years (mean, 48 years). Cancer of the colon was diagnosed in 51 men, and cancer of the rectum in 42 (all were adenocarcinomas). Adjusted for weight and age, the tertile of men with shortest height had a relative risk (95% confidence limits) of rectum cancer of 3.1 (1.0-9.0, p = 0.04), compared with the tallest tertile. Compared with the tertile of men who weighed the most, the tertile of men who weighed the least had an increased risk of 2.5 (0.9-6.9, p = 0.08) after adjustment for age and height. Compared with men who were in the highest tertile of both height and weight, the men in the lowest tertile of both height and weight had and increased risk of 5.5 (1.2-24.9, p = 0.02). There were no significant differences in height and weight between colon cancer cases and non-cases, but colon cancer cases had a significantly lower body mass index (kg/m2), 24.4 versus 25.3 (p = 0.03). Potentially confounding factors, such as smoking, alcohol, coffee consumption, physical activity on the job and in leisure time, and social class, had no influence on the results. We conclude that low height and low weight were strong predictors of rectal cancer, and that the least obese men had the highest risk of colon cancer.
Am J Clin Nutr (United States), May 1994, 59(5 Suppl) p1143S-1152S
Frentzel-Beyme R; Chang-Claude J
The study assessed mortality and morbidity risks as related to nutritional status of moderate and strict vegetarians in Germany. The total cohort of 1904 self-identified persons was followed up for 11 y. Compared with national mortality rates for Federal Republic of Germany, the observed deaths for all causes were below expectation by a factor of 0.44 for men and 0.53 for women. The mortality for colon cancer was reduced [standardized mortality ration (SMR 44.1 for men and 77.9 for women]. No deaths were observed from rectal cancer. A vegetarian lifestyle of long duration ( or = 20 y) was associated with decreased overall and cancer mortality. Other determinants of decreased cause-specific mortality were physical activity, body weight, and strictness of adherence to the life-style. The relationship between a vegetarian and fiber-rich diet and a decreased risk for colon cancer has been reported in many studies. In this study, the influence of other factors such as health-conscious behavior and a healthy lifestyle seem to indicate partly stronger effects than nutrition itself. This may explain the generally better health of moderate vegetarians.