Hsieh Cc

Evidence of prenatal influences on breast cancer risk

Intrauterine exposure to high concentrations of endogenous pregnancy oestrogens may be important in the aetiology of breast cancer. In a nested case-control study we have assessed the relation between breast cancer risk and indicators of pregnancy oestrogen concentrations; pre-eclampsia/eclampsia is negatively related and measures of fetal size are positively related to oestrogen concentrations. Standard records for women born at Uppsala University Hospital between 1874 and 1954 were linked with records of invasive breast cancer cases, identified through their unique national registration numbers in the Swedish Cancer Registry during 1958-90. For each breast cancer case, we selected as potential controls female offspring of the first three mothers admitted to the hospital after the cases mother; only controls still living in Sweden and free from breast cancer when it was diagnosed in the case were finally included. Conditional logistic regression analysis was done for 458 breast cancer cases and 1197 matched controls. Pre-eclampsia/eclampsia was associated with a breast cancer rate ratio of 0.24 (95% confidence interval 0.09-0.70, p = 0.01). Linear trends for breast cancer incidence with increasing birth weight, birth length, and placental weight were positive but not significant. Thus, prenatal factors are important in breast carcinogenesis. Concentrations of pregnancy oestrogens may be one such factor, but other prenatal or perinatal factors cannot be excluded.

Parity, age at first childbirth, and risk of ovarian cancer

Increasing parity is associated with a reduction in the risk of ovarian cancer, but it is not clear whether this association applies to different histopathological types and to borderline tumours. Moreover, the temporal relations are poorly understood, and the possible role of age at first birth remains unequivocal. We have investigated these issues in a case-control study nested in a nationwide cohort of women born between 1925 and 1960 in Sweden. During follow-up until 1984, 3486 invasive ovarian cancers (2992 epithelial, 330 stromal, 149 germ-cell, 15 not classifiable) and 510 tumours of borderline malignant potential were diagnosed. 5 individually age-matched controls (total 19,980) were selected for each case woman. After simultaneous adjustment for parity and age at first birth, increasing parity was associated with a pronounced consistent decrease in relative risk of all invasive cancers (odds ratio for each additional birth 0.81 [95% Cl 0.77-0.85]), epithelial cancer (0.81 [0.77-0.86]), stromal cancer (0.84 [0.72-0.98]), and germ-cell cancer (0.71 [0.48-1.05]), but a less consistent decrease for borderline tumours (0.92 [0.81-1.04]). The risk of ovarian cancer decreased by about 10% for each 5-year increment in age at first childbirth (odds ratios 0.89 [0.84-0.94] epithelial cancer, 0.92 [0.77-1.10] stromal cancer, 0.92 [0.65-1.32] germ-cell cancer, 0.93 [0.80-1.09] borderline tumours). Because our findings cannot be readily explained by theories involving incessant ovulation or high serum concentrations of gonadotropins, new aetiological hypotheses are needed. Pregnancy-dependent clearance from the ovaries of cells that have undergone malignant transformation could explain the reproductive risk factors for ovarian cancer.

Obesity and renal cell cancer--a quantitative review.

Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies examining body weight in relation to kidney cancer, available in MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to studies assessing obesity as body mass index (BMI, kg m–2), or equivalent. The risk estimates and the confidence intervals were extracted from the individual studies, and a mixed effect weighted regression model was used. We identified 22 unique studies on each sex, and the quantitative analysis included 14 studies on men and women, respectively. The summary relative risk estimate was 1.07 (95% CI 1.05–1.09) per unit of increase in BMI (corresponding to 3 kg body weight increase for a subject of average height). We found no evidence of effect modification by sex. Our quantitative summary shows that increased BMI is equally strongly associated with an increased risk of renal cell cancer among men and women.

Diet during pregnancy in relation to maternal weight gain and birth size

Objective: Maternal weight gain has been consistently linked to birth weight but, beyond maternal energy intake, no macronutrient has been associated with either of them. We have examined whether maternal energy-adjusted intake of macronutrients is associated with either maternal weight gain or birth-size parameters.Design: Cohort study.Setting: University hospital in Boston, USA.Subjects: A total of 224 pregnant women coming for their first routine prenatal visit. The women were followed through delivery.Interventions: None. Pregnant womens dietary intake during the second trimester was ascertained at the 27th week of pregnancy through a food frequency questionnaire.Results: Intake of neither energy nor any of the energy-generating nutrients was significantly associated with birth size. In contrast, maternal weight gain by the end of the second trimester of pregnancy was significantly associated with energy intake (+0.9 kg/s.d. of intake; P∼0.006) as well as energy-adjusted intake of protein (+3.1 kg/s.d. of intake; P<10-4), lipids of animal origin (+2.6 kg/s.d. of intake; P<10−4) and carbohydrates (−5.2 kg/s.d. of intake; P<10−4).Conclusions: Although maternal weight gain is strongly associated with birth size, the indicated nutritional associations with weight gain are not reflected in similar associations with birth-size parameters. The pattern is reminiscent of the sequence linking diet to coronary heart disease (CHD) through cholesterol: diet has been conclusively linked to blood cholesterol levels and cholesterol levels are conclusively linked to this disease, even though the association of diet with CHD has been inconclusive and controversial.Sponsorship: This study was supported in part by Grant No. CA54220 from the National Institutes of Health

Low-carbohydrate–high-protein diet and long-term survival in a general population cohort

Objective:We have evaluated the effects on mortality of habitual low carbohydrate–high-protein diets that are thought to contribute to weight control.Design:Cohort investigation.Setting:Adult Greek population.Subjects methods:Follow-up was performed from 1993 to 2003 in the context of the Greek component of the European Prospective Investigation into Cancer and nutrition. Participants were 22 944 healthy adults, whose diet was assessed through a validated questionnaire. Participants were distributed by increasing deciles according to protein intake or carbohydrate intake, as well as by an additive score generated by increasing decile intake of protein and decreasing decile intake of carbohydrates. Proportional hazards regression was used to assess the relation between high protein, high carbohydrate and the low carbohydrate–high protein score on the one hand and mortality on the other.Results:During 113 230 persons years of follow-up, there were 455 deaths. In models with energy adjustment, higher intake of carbohydrates was associated with significant reduction of total mortality, whereas higher intake of protein was associated with nonsignificant increase of total mortality (per decile, mortality ratios 0.94 with 95% CI 0.89 –0.99, and 1.02 with 95% CI 0.98 –1.07 respectively). Even more predictive of higher mortality were high values of the additive low carbohydrate–high protein score (per 5 units, mortality ratio 1.22 with 95% CI 1.09 –to 1.36). Positive associations of this score were noted with respect to both cardiovascular and cancer mortality.Conclusion:Prolonged consumption of diets low in carbohydrates and high in protein is associated with an increase in total mortality.

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.

Birth weight as a predictor of breast cancer: a case–control study in Norway

The hypothesis that birth weight is positively associated with adult risk of breast cancer implies that factors related to intrauterine growth may be important for the development of this malignancy. Using stored birth records from the two main hospitals in Trondheim and Bergen, Norway, we collected information on birth weight, birth length and placenta weight among 373 women who developed breast cancer. From the same archives, we selected as controls 1150 women of identical age as the cases without a history of breast cancer. Information on age at first birth and parity were collected from the Central Person Registry in Norway. Based on conditional logistic regression analysis, breast cancer risk was positively associated with birth weight and with birth length (P for trend=0.02). Birth weights in the highest quartile (3730 g or more) were associated with 40% higher risk (odds ratio, 1.4, 95% confidence interval, 1.1–1.9) of breast cancer compared to birth weights in the lowest quartile (less than 3090 g). For birth length, the odds ratio for women who were 51.5 cm or more (highest quartile) was 1.3 (95% confidence interval, 1.0–1.8) compared to being less than 50 cm (lowest quartile) at birth. Adjustment for age at first birth and parity did not change these estimates. Placenta weight was not associated with breast cancer risk. This study provides strong evidence that intrauterine factors may influence future risk of breast cancer. A common feature of such factors would be their ability to stimulate foetal growth and, simultaneously, to influence intrauterine development of the mammary gland.

Dual effect of parity on breast cancer risk

This study examined whether breast cancer risk increased for a short period after childbirth, but decreased after a longer period of time. Data from an international case-control study on breast cancer conducted in the 1960s were used to study the modifying effect of age at enrolment on the relationship between parity and breast cancer risk, comparing first uniparous with nulliparous women, and then biparous versus uniparous women. The statistical analysis was performed by modelling through multiple logistic regression, adjusting for study site, age at menarche, menopausal status and obesity index. Comparing uniparous with nulliparous women, an early age at birth seems to be protective for all periods after birth, whereas a late age at birth imparts a higher risk than nulliparity in the period immediately after birth, which declines with the passage of time. The modification effect by age was not apparent when biparous women with different age at second birth were compared with uniparous women. The results support the hypothesis that pregnancy oestrogens impart a transient increase of maternal breast cancer risk when the full-term pregnancy occurs late in a womans life.

Pregnancy and risk of renal cell cancer: a population-based study in Sweden

Epidemiological findings indicate that hormonal influences may play a role in the etiology of renal cell cancer (RCC). The possible effect of childbearing remains enigmatic; while some investigators have reported a positive association between number of births and renal cell cancer risk, others have not. A case–control study, nested within a nation-wide Fertility Register covering Swedish women born 1925 and later, was undertaken to explore possible associations between parity and age at first birth and the risk of renal cell cancer. Among these women a total of 1465 cases of RCC were identified in the Swedish Cancer Register between 1958 and 1992 and information on the number of live childbirths and age at each birth was obtained by linkage to the Fertility Database. For each case, five age-matched controls were randomly selected from the same register. Compared to nulliparous women, ever-parous women were at a 40% increased risk of RCC (Odds Ratio [OR]=1.42; 95% CI 1.19-1.69). The corresponding OR for women of high parity (five or more live births) was 1.91 (95% CI 1.40–2.62). After controlling for age at first birth among parous women, each additional birth was associated with a 15% increase in risk (OR=1.15; 95% CI 1.08–1.22). The observed positive association between parity and renal cell cancer risk is unlikely to be fully explained by uncontrolled confounding, but warrants further evaluation in large studies, with allowance for body mass index.

Breast-feeding and breast cancer in the offspring

The causation of breast cancer in certain strains of mice by a virus that can be transmitted vertically, through the milk produced during lactation, has led to the hypothesis that a similar phenomenon could exist in humans. There have been laboratory-based studies in humans suggesting that a virus may be involved in the etiology of female breast cancer although other investigations did not support this hypothesis. Descriptive data and epidemiologic evidence of ecologic nature do not indicate a role of lactation in the causation of human breast cancer, but the hypothesis has not been adequately assessed in analytic epidemiologic studies. A nested case-control study undertaken in Sweden to examine the role of prenatal factors on breast cancer risk in the offspring, allowed the evaluation of the importance of breast-feeding in the causation of this disease. Standardised records concerning women born at the Uppsala University Hospital from 1874 to 1954 were linked with invasive breast cancer incident cases, identified through their unique national registration number in the Swedish Cancer Registry during 1958-1990. For each case with breast cancer, the females born to the first three mothers admitted after the cases mother were selected as potential matching controls. Only controls living in Sweden and free from breast cancer until the time of diagnosis of breast cancer in the corresponding case were eventually included in the study. The analysis was based on 458 cases of breast cancer born in singleton pregnancies and 1,197 singleton age- and birth date-matched controls. Breast-feeding was not a significant or suggestive risk factor for breast cancer in the offspring; compared to women who at discharge were wholly or partly breastfed, women who as newborn were not breastfed had a relative risk of breast cancer of 0.97 with 95% confidence interval 0.44-2.17 (P = 0.95).