Loren Lipworth

Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis : an assessment of the biological and epidemiological evidence

There is an increasing public and scientific concern that certain chlorinated compounds, recognized as environmental pollutants, may cause estrogen-related neoplastic disease in humans. The main hypothesis has been that certain organochlorines, through their estrogenic actions, might cause breast cancer. From experimental studies, both in vitro and in vivo, there is evidence that certain organochlorine compounds may cause estrogenic effects, whereas others may cause antiestrogenic effects. In limited studies, some of these compounds in high doses have also been shown to increase and reduce the frequency of estrogen-related tumors in animals. The epidemiological findings regarding the association between organochlorines and breast cancer are inconclusive. However, the largest and best designed study has been interpreted as negative with respect to DDT and polychlorinated biphenyls (PCB) in relation to breast cancer. Associations between organochlorine exposure and endometrial cancer or endometriosis have even more limited empirical basis. The hypothesis that human exposure to environmental levels or organochlorines would favor an estrogenic overactivity leading to an increase in estrogen-dependent formation of mammary or endometrial tumors is not supported by the existing in vitro, animal and epidemiological evidence. It can, however, not be conclusively rejected on the basis of available data.

Olive oil, other dietary fats, and the risk of breast cancer (Italy).

Data from a multicenter case-control study on breast cancer conducted in Italy have been used to analyze the relationship of olive oil and other dietary fats to breast cancer risk. Cases were 2,564 women hospitalized with histologically confirmed, incident breast cancer. Controls were 2,588 women admitted to the same network of hospitals for acute, non-neoplastic, non-hormone related, on-digestive tract disorders. Cases and controls were interviewed between 1991 and 1994 using a validated food-frequency questionnaire. The data were modelled through multiple logistic regression controlling for demographic and reproductive breast-cancer risk factors, energy intake and, mutually, for types of dietary fat. For olive oil, compared with the lowest quintile, the odds ratios (OR) were 1.05, 0.99, 0.93, and 0.87 for increasing quintiles of intake; in a model postulating linear logit increase, the OR per unit (30g) was 0.89 (95 percent confidence interval [CI]=0.81–0.99, P=0.03). Among other oils or fats considered, the OR for the highest level of intake was 0.72 (CI=0.6–0.9) for a group of specific seed oils (including safflower, maize, peanut, and soya) compared with nonusers. The ORs for the highest cf lowest level of intake were 0.80 for mixed or unspecified seed oils, 0.95 for butter, and 0.96 for margarine. The study, based on a large dataset from various Italian regions, shows an inverse relationship of breast cancer risk with intake of olive oil and other vegetable oils, but not with butter or margarine.

Organochlorine compounds and estrogen-related cancers in women

The organochlorines, a diverse group of some 15,000 compounds, have been implicated increasingly as being harmful to humans. Some congeners of DDT and PCB elicit very weak to weak estrogenic responses in animals, while the dioxin TCDD and related compounds have antiestrogenic properties. This review summarizes the evidence regarding whether certain organochlorine compounds, usually as persistent food-chain contaminants, increase the risk of breast and endometrial cancers through their estrogenic potential. In humans, neither ecologic data nor occupational studies provide clear support for an association between organochlorine exposure and the occurrence of these cancers. In our summary analysis of occupational exposure, the rate ratio of breast cancer for exposed cf unexposed women was 0.84 (95 percent confidence interval [CI]=0.50–1.33) for PCBs and 1.08 (CI=0.68–1.58) for TCDD. Similarly, effect estimates close to unity were found in summary analysis of breast cancer case-control studies regarding levels of DDE and PCB in adipose tissue or serum. In two recent nested case-control studies using stored specimens, the odds ratio per standard deviation increase in serum p,p-DDE was 1.27 (CI=0.95–1.69). Although estrogenic effects of certain organochlorine compounds should be easier to detect on the endometrium, we know of no analytic epidemiologic studies of endometrial cancer published to date. We conclude that available data do not indicate that organochlorines will affect the risk of these two cancers in any but the most unusual situation.

Diet and risk of esophageal cancer by histologic type in a low-risk population

In a hospital‐based case‐control study of esophageal cancer undertaken in Athens (1989–1991), 43 patients with incident esophageal squamous‐cell carcinoma and 56 patients with incident esophageal adenocarcinoma were compared to 200 injury patients. Personal interviews were conducted in the hospital setting, and dietary intake was assessed using a validated semi‐quantitative food‐frequency questionnaire. Nutrient intakes for individuals were calculated by multiplying the nutrient content of a typical portion size for each specified food item by the frequency with which the food was consumed per month and summing these estimates for all food items. Data were modeled through logistic regression, controlling for socio‐demographic factors, tobacco smoking, consumption of alcoholic beverages and total energy intake. Consumption of vegetables and fruits as well as intake of vitamin A, vitamin C and crude fiber were inversely associated with esophageal cancer in general, but the respective associations were stronger for adenocarcinoma. There was evidence that added oils and fats and intake of polyunsaturated fat were positively associated with adenocarcinoma but inversely associated with squamous‐cell carcinoma.

A Case-Control Study of Endometrial Cancer in Relation to Reproductive, Somatometric, and Life-Style Variables

A hospital-based case-control study of cancer of the endometrium was conducted in Athens, Greece, from 1992 to 1994. The cases were 145 women residents of Greater Athens with histologically confirmed incident cancer of the endometrium, operated in the two cancer hospitals of the Greater Athens area or the major University Department of Obstetrics and Gynecology. Controls were 298 women residents of Greater Athens hospitalized for bone fractures or other orthopedic conditions in the accident hospital of Greater Athens. The data were analyzed by modeling through multiple logistic regression. The risk of endometrial cancer decreased with the number of livebirths (p for trend < 0.01), with early age at menopause (p = 0.03), and with later age at menarche (p = 0.11), whereas miscarriages and induced abortions were clearly unrelated. There were nonsignificant relations of disease risk with smoking (inverse), alcohol (inverse), and menopausal estrogens (positive), whereas oral contraceptive use was too uncommon to allow meaningful study. The lower risk of the disease associated with current occupations requiring manual activity (p = 0.03) and the lower, although not significantly so (p = 0.36), energy intake of cases in comparison to controls suggest that physical inactivity could be an important risk factor for endometrial cancer. Women with endometrial cancer were significantly taller than control women (p = 0.02). The latter results indicate that excess energy intake in early life, leading to higher attained stature, and excessive energy intake in later life, on account of physical inactivity and leading to higher body weight, converge in increasing the risk for endometrial cancer.

Dietary factors and the risk of endometrial cancer: a case--control study in Greece.

In a hospital-based case-control study of endometrial cancer undertaken in Athens (1992-94), 145 women residents of Greater Athens with confirmed cancer of the endometrium were compared with 298 control patients with orthopaedic diseases. Personal interviews were conducted in the hospital setting, and diet was assessed using a validated semiquantitative food frequency questionnaire. Nutrient intakes for individuals were calculated by multiplying the nutrient intake of a typical portion size for each specified food item by the frequency at which the food was consumed per month and summing these estimates for all food items. Data were modelled through logistic regression, controlling for demographic, reproductive and somatometric risk factors for endometrial cancer as well as for total energy intake. No macronutrient was significantly associated with endometrial cancer risk, but increasing intake of monounsaturated fat, mostly olive oil, by about one standard deviation was associated with a 26% risk reduction (odds ratio = 0.74; 95% confidence interval 0.54-1.3). Among micronutrients, only calcium intake was significantly inversely associated with endometrial cancer risk, whereas there was evidence against retinol and zinc imparting protection against the disease. With respect to food groups, there was weak and non-significant evidence that vegetables are protective, whereas consumption of pulses was positively associated with disease possibly because they contribute substantially in Greece to energy intake in excess of physical activity-dependent requirements.

Serum steroid hormone levels, sex hormone-binding globulin, and body mass index in the etiology of postmenopausal breast cancer

Serum concentrations of estrone, androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured postoperatively in 122 postmenopausal women with incident breast cancer and 122 age-matched population controls. After mutual adjustment, through conditional logistic regression, between the hormonal variables and body mass index (BMI), the odds ratios for increasing control-defined quartiles of estrone and androstenedione, respectively, were 1.00, 1.44, 1.76, 1.94 and 1.00, 0.83, 0.97, 2.43; there was no association of testosterone with breast cancer risk. Moreover, the odds ratios for increasing quartiles of SHBG and BMI were 1.00, 0.72, 0.28, 0.25 and 1.00, 0.39, 0.28, 0.19, respectively. This study reveals sharp contrasts in breast cancer risk between women with high estrone and low BMI and SHBG, us women with low estrone and high BMI and SHBG.

LIFE-STYLE FACTORS AND MEDICAL CONDITIONS IN RELATION TO ESOPHAGEAL CANCER BY HISTOLOGIC TYPE IN A LOW-RISK POPULATION

A case‐control study of esophageal cancer was conducted in Athens, Greece, during the 3‐year period 1989–1991. Cases were 43 patients with incident esophageal squamous‐cell carcinoma and 56 patients with incident esophageal adenocarcinoma hospitalized in any one of the 9 major hospitals in Athens, whereas controls were 200 injury patients admitted to the only Athens accident hospital. The data were analyzed by modeling through multiple logistic regression. Tobacco smoking and alcohol drinking were associated with both histologic types, but the odds ratios were generally lower than those observed in several other investigations. It may be that the high consumption of vegetables and fruits by the Greek population cushions the deleterious effect of tobacco, while the intake of ethanol in the form of wine during meals reduces the impact of this substance on the esophageal mucosa. A preference for very hot temperature for beverages and food was associated with significant elevation of the odds ratio to about 1.8 for esophageal cancer in general. There was non‐significant evidence in our data to support earlier reports that aspirin intake may reduce the risk of cancer of the esophagus. Overall, we found no striking difference in the risk profile of the 2 histologic types of esophageal cancer.

Maternal pregnancy hormone levels in an area with a high incidence (Boston, USA) and in an area with a low incidence (Shanghai, China) of breast cancer

SummaryCharacteristics probably associated with the fetal hormonal milieu have recently been shown to increase (birth size indicators, prematurity, neonatal jaundice) or decrease (pregnancy toxaemia) breast cancer risk in the female offspring. However, it is unknown whether differences in pregnancy hormone levels may contribute to the marked geographical variation in breast cancer incidence. We have compared, in a highly standardized manner, pregnancy hormone levels in a population with high incidence and one with low incidence of breast cancer. Three hundred and four pregnant Caucasian women in Boston and 334 pregnant Chinese women in Shanghai were enrolled from March 1994 to October 1995. Levels of oestradiol, oestriol, prolactin, progesterone, human growth hormone, albumin and sex hormone-binding globulin were measured in maternal blood at weeks 16 and 27 of gestation and compared between the two study sites using non-parametric Wilcoxon’s rank-sum test. Demographical, anthropometrical and pregnancy characteristics were ascertained through interview, and relevant variables concerning delivery and the newborn were abstracted from medical records and paediatric charts. During the first visit, median serum levels of all studied hormones were statistically significant, and in most instances substantially, higher among Chinese women, who have a low incidence of breast cancer, compared with American women, who have a high incidence of breast cancer. An analogous pattern was evident during the second visit, although the relative differences tended to be smaller. Further research is needed to identify lifestyle or other exogenous determinants of pregnancy hormone levels, as well as possible mechanisms by which they may influence carcinogenic processes in the breast and possibly other organs.

Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin in the USA and China

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics.