B. E. Henderson

Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma

Aflatoxins have long been suspected to be human hepatic carcinogens but no direct study was feasible until assays to measure individual aflatoxin exposure became available. We have used assays for urinary aflatoxin B1, its metabolites AFP1 and AFM1, and DNA-adducts (AFB1-N7-Gua) to assess the relation between aflatoxin exposure and liver cancer, as part of an ongoing prospective study of 18,244 middle-aged men in Shanghai, Peoples Republic of China. After 35,299 person-years of follow-up, 22 cases of liver cancer had been identified. For each case, 5 or 10 controls were randomly selected from cohort members without liver cancer on the date the disorder was diagnosed in the case and matched to within 1 year for age, within 1 month for sample collection, and for neighbourhood of residence. Subjects with liver cancer were more likely than were controls to have detectable concentrations of any of the aflatoxin metabolites (relative risk 2.4, 95% confidence interval 1.0-5.9). The highest relative risk was for aflatoxin P1 (6.2, 1.8-21.5). In an analysis adjusting for the effects of hepatitis B surface antigen seropositivity, level of education, cigarette smoking, and alcohol consumption, the relative risk for the presence of aflatoxin metabolites was 3.8 (1.2-12.2). There was a strong interaction between serological markers of chronic hepatitis B infection and aflatoxin exposure in liver-cancer risk. Reduction of aflatoxin exposure may be a useful intermediate goal in prevention of liver cancer, since the benefits of wide-scale hepatitis B vaccination will not be apparent for many years.

5-alpha-reductase activity and risk of prostate cancer among japanese and US white and black males

The incidence of prostate cancer varies widely between countries and ethnic groups. Black-Americans have the highest incidence rates world wide, whereas native Japanese have among the lowest. The reasons for this risk differential are unknown, although we have previously shown that higher circulating testosterone concentrations in young adult black men compared with young adult white men may explain the underlying differences in subsequent prostate cancer incidence between these two populations. We have now compared serum testosterone concentrations in young adult Japanese men with those of young adult whites and blacks, but found no significant differences. However, these white and black men had significantly higher values of 3 alpha, 17 beta androstanediol glucuronide (31% and 25% higher, respectively) and androsterone glucuronide (50% and 41% higher, respectively) than Japanese subjects. These two androgens are indices of 5 alpha-reductase activity. Our results raise the possibility that reduced 5 alpha-reductase activity has a role in producing the low prostate cancer incidence rates among Japanese. This finding may have important implications for prostate cancer prevention.

Alcohol, physical activity and other risk factors for colorectal cancer: a prospective study

The aetiology of colorectal cancer was studied in a cohort of 11,888 residents of a retirement community. After four and one-half years of follow-up, 58 male and 68 female incident colorectal cancers were identified. Daily alcohol drinkers experienced nearly a two-fold increase in risk (2 sided P = 0.002). Colorectal cancer was also positively associated with Quetelets index and inversely associated with avocational physical activity. The results were consistent for both sexes but were statistically significant only for males. With the exception of dietary vitamin C, none of the nutrients under study (i.e., vitamins A and E, dietary fibre, calcium, and beta carotene) showed a significant association with colorectal cancer. An inverse relationship between colorectal cancer and dietary vitamin C was observed in females, but there was no association with either vitamin C from supplements or with total vitamin C intake. Males and females who had 3 or more children showed a significantly reduced risk of colorectal cancer (RR = 0.45, 95% CI = 0.2, 0.9), but those with no children did not show the highest risk.

Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study.

A cohort of 11,580 residents of a retirement community initially free from cancer were followed from 1981 to 1989. A total of 1,335 incident cancer cases were diagnosed during the period. Relative risks of cancer were calculated for baseline consumption of vegetables, fruits, beta-carotene, dietary vitamin C, and vitamin supplements. After adjustment for age and smoking, no evidence of a protective effect was found for any of the dietary variables in men. However, an inverse association was observed between vitamin C supplement use and bladder cancer risk. In women, reduced cancer risks of all sites combined and of the colon were noted for combined intake of all vegetables and fruits, fruit intake alone, and dietary vitamin C. Supplemental use of vitamins A and C showed a protective effect on colon cancer risk in women. There was some suggestion that beta-carotene intake and supplemental use of vitamin A, C, and E were associated with reduced risk of lung cancer in women, but none of these results were statistically significant. These inverse associations observed in women seem to warrant further investigation, although there was inconsistency in results between the sexes.

MENOPAUSAL OESTROGEN THERAPY AND PROTECTION FROM DEATH FROM ISCHAEMIC HEART DISEASE

The medical records of a Los Angeles retirement community were examined to find out the association between oestrogen replacement therapy and death from ischaemic heart disease. Women dying from ischaemic heart disease over a five-year period were compared with living and deceased control groups; both controls were matched with cases for date of birth, date of entry into the community, race, and socioeconomic status. The deceased control was also matched for date of death. Compared with living controls cases using conjugated oestrogens had a risk ratio for death from ischaemic heart disease of 0.43 (95% confidence interval 0.24-0.75). Comparison with deceased controls gave a similar relative risk. This association was not due to identifiable confounding factors. Other risk factors for ischaemic heart disease, including hypertension, diabetes, stroke, angina pectoris, and heavy cigarette smoking, were confirmed by this study.

Diet and breast cancer in Shanghai and Tianjin, China.

Various aspects of adult diet have been linked to breast cancer development. These include intake of fat (risk factor), and intake of fibre, soy protein and vitamins A, C and E (protective factors). Results of previous studies have been inconsistent. We examined the possible associations between breast cancer and various indices of nutrient and food intake in two Chinese populations who are at relatively low risk for breast cancer (one-fifth the rate in US white women). Two case-control studies of breast cancer were conducted in the cities of Shanghai and Tianjin, China. In Shanghai, 534 women aged 20-69 years with histologically confirmed breast cancer were recruited, whereas in Tianjin 300 women aged 20-55 years with histologically confirmed breast cancer were interviewed. All controls were community controls who were individually matched to the cases by sex and age (case-control ratio = 1:1). All interviews were conducted in person. Findings from the two studies were similar, although the diets in Shanghai and Tianjin were different in many respects. Cases and controls were similar in their consumption of soy protein, measured either in absolute levels or as percentages of total protein. Overall, all components of dietary fat (saturated fat, monounsaturated fat, polyunsaturated fat) showed a modest, non-significant association with breast cancer after adjustment for energy intake and other non-dietary risk factors for breast cancer. Intake of crude fibre, carotene and vitamin C, on the other hand, exhibited strong, statistically significant inverse associations with breast cancer risk. The last three indices were highly correlated, rendering it impossible to disentangle their individual effects; they were closely associated with intake of green vegetables in the two study populations. Vitamin E intake was unrelated to breast cancer risk in Shanghai and Tianjin. In the multivariate logistic regression model which included all non-dietary risk factors for breast cancer and energy intake, Shanghai women in the lowest tertile of crude fibre intake and highest tertile of fat intake had a 2.9-fold increased risk for breast cancer relative to those in the highest tertile of crude fibre intake and lowest tertile of fat intake. The comparable relative risk in Tianjin women was 2.4. Our data indicate a strong protective effect against breast cancer development with intake of foods rich in fibre, vitamin C and carotene. Our results are also compatible with dietary fat having a modest, positive effect on breast cancer risk within the range of exposure experienced by women in China.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal chemoprevention of cancer in women

The use of oral contraceptives in the United States during the past three decades has led to a dramatic decline in the incidence of cancers of the ovary and endometrium. The magnitude of these declines was predictable both from epidemiologic data and from the biologic effects of oral contraceptives on these tissues. Although the incidence of breast cancer has not been substantially affected by current oral contraceptives, it may be possible to develop alternative forms of contraception that provide protection against all three cancers. The major goal of hormonal chemoprevention of cancer is to reduce cell proliferation in the relevant epithelial tissue. New chemopreventive agents such as tamoxifen exemplify the application of this principle.

Oral contraceptive use and early abortion as risk factors for breast cancer in young women.

A case-control study was conducted in Los Angeles County, California, of 163 very young breast-cancer cases (all aged 32 or less at diagnosis) to investigate the role, if any, of oral contraceptives (OC) in the development of the disease. OC use before first full-term pregnancy (FFTP) was associated with an elevated risk, which increased with duration of OC use (relative risk approximately 2.2 at 6 years of use, P < 0.01). This increased risk could not be explained by other risk factors. OC use after FFTP was not associated with any change in risk. A first-trimester abortion before FFTP, whether spontaneous or induced, was associated with a 2.4-fold increase in breast-cancer risk (P < 0.005).

The effects of moderate physical activity on menstrual cycle patterns in adolescence: Implications for breast cancer prevention

Girls who engage in strenuous physical activity are often amenorrheic and have recently been reported to be at a reduced risk of breast cancer. To determine whether moderate amounts of exercise affect menstrual cycle patterns and ovulatory frequency in young postmenarcheal girls, the menstrual cycles and physical activity patterns of 168 high school girls were monitored for a 6 month period. Anovulatory cycles were associated with later age at menarche, fewer elapsed years since menarche and greater levels of energy expended per week in physical activity. After adjusting for age at menarche and years since menarche, there was a significant dose-related trend in the risk of anovular menstrual cycles associated with increasing levels of physical activity (1-sided P = 0.03). Major determinants of average cycle length were weekly average energy expenditure (less than or equal to 750 kcal wk-1 associated with cycles that were on average 2.4 days longer), age at menarche (an increase of 0.7 days per year of age) and race (Asians having cycles about 1.9 days longer than Caucasians). Because a major determinant of breast cancer risk may be the cumulative number of ovulatory cycles, these data suggest that regular participation in moderate physical activity, by reducing the frequency of ovulatory cycles in adolescence, may provide an opportunity for the primary prevention of breast cancer.

Vasectomy, cigarette smoking, and age at first sexual intercourse as risk factors for prostate cancer in middle-aged men.

A population-based case-control study was conducted in men aged 60 or less to assess the risk of prostate cancer associated with vasectomy and other factors. Data were obtained from 216 case-control pairs by telephone interviews; this number represented 55% of all eligible cases. The matched pairs relative risk (RR) for vasectomy in ever married men was 1.4 with a 95% confidence interval (CI) of 0.9-2.3. There was a positive association between the number of years since vasectomy and prostate cancer risk (1-sided P = 0.01). Early age at first sexual intercourse was associated with increased prostate cancer risk (age less than 17 vs. 21+, RR = 2.3, 95% CI = 1.3, 4.0) but there were no consistent associations with number of sexual partners or frequency of sexual intercourse. Cigarette smoking was also associated with increased risk of prostate cancer (RR = 1.9, 95% CI = 1.2, 3.0) and there was a positive dose-response relationship with years of smoking (1-sided P = 0.001). We discuss the possible implication of the low response rate on each of these findings. To determine whether the association with vasectomy might have a hormonal basis, we compared levels of testosterone (T) and testosterone binding globulin-binding capacity (TeBG-bc) in 33 of the vasectomized control men with levels in 33 non-vasectomized controls of the same age, weight and height. T levels were higher in vasectomized than in non-vasectomized controls (1-sided P = 0.06). The ratio of T to TeBG-bc (an index of bioavailable T) was 13.5% higher in vasectomized men (1-sided P = 0.03).