Gianluca Severi

Use of menopausal hormone therapy and ovarian cancer risk in a French cohort study

Abstract Background Epidemiological studies have found that menopausal hormone therapy (MHT) use is associated with an increased ovarian cancer risk. However, whether different MHT types confer the same level of risk is unclear. We estimated the associations between different MHT types and the risk of ovarian cancer in a prospective cohort. Methods The study population included 75 606 postmenopausal women from the E3N cohort. Exposure to MHT was identified from self-reports in biennial questionnaires between 1992 and 2004 and from drug claim data matched to the cohort between 2004 and 2014. Hazard ratios and 95% confidence intervals (CIs) of ovarian cancer were estimated using multivariable Cox proportional hazards models with MHT as a time-varying exposure. Tests of statistical significance were 2-sided. Results Over an average 15.3 years follow-up, 416 ovarian cancers were diagnosed. Hazard ratios of ovarian cancer associated with ever use of estrogens combined with progesterone or dydrogesterone and ever use of estrogens combined with other progestagen were equal to 1.28 (95% CI = 1.04 to 1.57) and 0.81 (95% CI = 0.65 to 1.00), respectively (Phomogeneity = .003), compared with never use. The hazard ratio for unopposed estrogen use was 1.09 (95% CI = 0.82 to 1.46). We found no trend according to duration of use or time since last use except for estrogens combined with progesterone or dydrogesterone, which showed decreasing risk with increasing time since last use. Conclusion Different MHT types may impact ovarian cancer risk differentially. The possibility that MHT containing progestagens other than progesterone or dydrogesterone may confer some protection should be evaluated in other epidemiological studies.

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

AbstractObesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow‐up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05‐1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01‐1.96), postmenopausal breast (HR = 1.08; 1.00‐1.16) and thyroid (HR = 1.40; 1.04‐1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity‐related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06‐1.33), ovary (HR = 1.40; 1.04‐1.91), corpus uteri (HR = 1.42; 1.06‐1.91), kidney (HR = 1.80; 1.20‐2.68) and pancreas in men (HR = 1.81; 1.11‐2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23‐0.69) and colon (HR = 0.69; 0.52‐0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.