Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis

A sedentary lifestyle, obesity, and a Westernized diet have been implicated in the aetiology of both colorectal cancer and non-insulin dependent diabetes mellitus, leading to the hypothesis that hyperinsulinaemia may promote colorectal cancer. We prospectively examined the association between colorectal cancer risk and factors related to insulin resistance and hyperinsulinaemia, including BMI, physical activity, diabetes mellitus, and blood glucose, in a cohort of 75 219 Norwegian men and women. Information on incident cases of colorectal cancer was made available from the Norwegian Cancer Registry. Reported P values are two-sided. During 12 years of follow up, 730 cases of colorectal cancer were registered. In men, but not in women, we found a negative association with leisure-time physical activity (P for trend = 0.002), with an age-adjusted RR for the highest versus the lowest category of activity of 0.54 (95% CI = 0.37–0.79). Women, but not men, with a history of diabetes were at increased risk of colorectal cancer (age-adjusted RR = 1.55; 95% CI = 1.04–2.31), as were women with non-fasting blood glucose ≥8.0 mmol l−1(age-adjusted RR = 1.98; 95% CI = 1.31–2.98) compared with glucose <8.0 mmol l−1. Overall, we found no association between BMI and risk of colorectal cancer. Additional adjustment including each of the main variables, marital status, and educational attainment did not materially change the results. We conclude that the inverse association between leisure-time physical activity and colorectal cancer in men, and the positive association between diabetes, blood glucose, and colorectal cancer in women, at least in part, support the hypothesis that insulin may act as a tumour promoter in colorectal carcinogenesis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study

We examined the relationship of body mass index (BMI), diabetes and smoking to endometrial cancer risk in a cohort of 36 761 Norwegian women during 15.7 years of follow-up. In multivariable analyses of 222 incident cases of endometrial cancer, identified by linkage to the Norwegian Cancer Registry, there was a strong increase in risk with increasing BMI (P-trend <0.001). Compared to the reference (BMI 20–24 kg m−2), the adjusted relative risk (RR) was 0.53 (95% confidence interval (CI): 0.19–1.47) for BMI<20 kg m−2, 4.28 (95% CI: 2.58–7.09) for BMI of 35–39 kg m−2 and 6.36 (95% CI: 3.08–13.16) for BMI⩾40 kg m−2. Women with known diabetes at baseline were at three-fold higher risk (RR 3.13, 95% CI: 1.92–5.11) than those without diabetes; women who reported current smoking at baseline were at reduced risk compared to never smokers (RR 0.55, 95% CI: 0.35–0.86). The strong linear positive association of BMI with endometrial cancer risk and a strongly increased risk among women with diabetes suggest that any increase in body mass in the female population will increase endometrial cancer incidence

Socio-economic and lifestyle factors associated with the risk of prostate cancer

International and interethnic differences in prostate cancer incidence suggest an environmental aetiology, and lifestyle and socio-economic factors have been studied, but with divergent results. Information on a cohort of 22 895 Norwegian men aged 40 years and more was obtained from a health examination and two self-administered questionnaires. Information on incident cases of prostate cancer was made available from the Cancer Registry. We used the Cox proportional hazards model to calculate incidence rate ratios as estimates of the relative risk (RR) with 95% confidence interval (CI). Reported P -values are two-sided. During a mean follow-up of 9.3 years, 644 cases were diagnosed. Risk was elevated among men in occupations of high compared to low socio-economic status (RR = 1.30; 95% CI 1.05–1.61), and among men with high education compared to the least educated (RR = 1.56; 95% CI 1.11–2.19). A RR of 1.56 (95% CI 0.97–2.44) suggests a higher risk among divorced or separated men, compared with married men. We also found indications of a weak negative association with leisure-time physical activity (RR = 0.80; 95% CI 0.62–1.03 for high vs low activity), a weak positive association with increasing number of cigarettes (P = 0.046), while alcohol consumption was not related to the risk of prostate cancer. These results show that high socio-economic status is associated with increased risk of prostate cancer, and that divorced or separated men might be at higher risk than married men. Data from this study also indicate that high levels of physical activity may reduce prostate cancer risk. © 2000 Cancer Research Campaig

The negative association between pre-eclampsia and breast cancer risk may depend on the offspring's gender

If the negative association between pre-eclampsia and subsequent breast cancer risk differs by gender, this would strengthen the hypothesis that factors intrinsic to the particular pregnancy may explain the association. The study included 701 006 parous Norwegian women with follow-up for breast cancer through the Cancer Registry of Norway. Breast cancer risk was lower in women with pre-eclampsia/hypertension in their first pregnancy, compared to other women (relative risk, 0.86, 95% CI, 0.78–0.94), after adjustment for age at first birth, maternal birth year, length of gestation, marital status, and parity. The risk reduction was slightly greater if the woman delivered a son as opposed to a daughter (relative risks of 0.79 vs 0.94, P-value for interaction, 0.06), and if pre-eclampsia/hypertension was combined with pre-term delivery, these differences were more pronounced (relative risks, 0.62 vs 1.07, P-value for interaction 0.03). A subanalysis among 176 036 primiparous women showed a substantial risk reduction if the mother delivered a son (relative risk, 0.62, 95% CI, 0.47–0.82), but essentially null if she delivered a daughter (relative risk, 0.92, 95% CI, 0.72–1.18; P-value for interaction, 0.05). These results suggest that the effect of pre-eclampsia/hypertension may be attributed to factors associated with the particular pregnancy rather than an underlying biological trait of the mother. The stronger risk reduction related to having a son suggests a role for sex-dependent hormones in pregnancy

Pregnancy related protection against breast cancer depends on length of gestation

In a prospective study of 694 657 parous women in Norway, 5474 developed breast cancer after their first birth. If the first pregnancy lasted less than 32 weeks, the risk was 22% (95% confidence interval, −3% to 53%) greater than after a pregnancy of 40 weeks or more, with a significant declining trend in risk (P for trend=0.02)

Concentrations of human chorionic gonadotrophin in very early pregnancy and subsequent pre-eclampsia: a cohort study Downloaded from

study question: Are low serum concentrations of human chorionic gonadotrophin (hCG) in very early pregnancy associated with pre-eclampsia risk? summary answer: Low hCG concentrations in very early pregnancy are associated with increased risk of severe pre-eclampsia. what is known already: Low maternal serum concentrations of hCG early in pregnancy may indicate impaired proliferation or invasion of trophoblast cells, and thus low hCG concentrations may serve as a marker for impaired placental development. Impaired placental development is assumed to be a cause of pre-eclampsia, but there is little prospective evidence to support this hypothesis. study design, size, duration: We performed a prospective cohort study of pregnancies after IVF at Oslo University Hospital 1996 -2010 with linkage to the Medical Birth Registry of Norway to obtain information on pre-eclampsia development. participants/materials, setting, methods: We included 2405 consecutive singleton pregnancies and examined the association of maternal serum hCG concentrations (measured using Elecsys, Roche) on Day 12 after embryo transfer with the risk of any pre-eclampsia and of mild and severe pre-eclampsia. main results and the role of chance: HCG concentrations were inversely associated with pre-eclampsia risk in a dose-dependent manner (P trend 0.02). Compared with women with hCG ≥150 IU/l, women with hCG ,50 IU/l were at 2-fold higher overall risk of pre-eclampsia [absolute risk 6.4 versus 2.8%; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.7]. The inverse association was restricted to severe pre-eclampsia (P trend 0.01), thus, women with hCG ,50 IU/l were at 4-fold higher risk of severe pre-eclampsia than women with hCG ≥150 IU/l (absolute risk 3.6 versus 0.9%; OR 4.2, 95% CI 1.4 -12.2). For mild pre-eclampsia, there was no corresponding association (P trend 0.36). limitations, reasons for caution: Results for IVF pregnancies may not be generalizable to spontaneously conceived pregnancies. wider implications of the findings: Plausible causes of low maternal hCG concentrations very early in pregnancy include impaired placental development and delayed implantation. Thus, these results provide prospective evidence to support the hypothesis that impaired placental development may be associated with subsequent development of severe pre-eclampsia. study funding/competing interest: The study was financially supported by the Research Council of Norway. None of the authors has any conflict of interest to declare

Intrauterine environment, mammary gland mass and breast cancer risk

Two intimately linked hypotheses on breast cancer etiology are described. The main postulate of the first hypothesis is that higher levels of pregnancy estrogens and other hormones favor the generation of a higher number of susceptible stem cells with compromised genomic stability. The second hypothesis postulates that the mammary gland mass, as a correlate of the number of cells susceptible to transformation, is an important determinant of breast cancer risk. A simple integrated etiological model for breast cancer is presented and it is indicated that the model accommodates most epidemiological aspects of breast cancer occurrence and natural history