Luigino Dal Maso

Adherence to a Cholesterol‐Lowering Diet and the Risk of Female Hormone‐Related Cancers: An Analysis From a Case–Control Study Network

ABSTRACTObjectiveWe investigated the association between a cholesterol‐lowering diet score and the risk of female hormone‐related cancers.DesignWe used data on 2108 breast, 367 endometrial, 869 ovarian cancer cases and corresponding controls from an Italian network of case–control studies.SettingHospital‐based.SampleBreast, endometrial, and ovarian cancer cases and controls.MethodsWe assessed the adherence to a cholesterol‐lowering diet using a score based on seven dietary components: high intake of non‐cellulosic polysaccharides, monounsaturated fatty acids, legumes, seeds/corn oil; low intake of saturated fatty acids, dietary cholesterol, and glycaemic index. We assigned one point for each component if the requirement was met; otherwise, we assigned zero. The overall score was calculated by summing up points over the seven components, ranging from 0 (null) to 7 (complete adherence).Main Outcome MeasuresOdds ratios (ORs) and 95% confidence intervals (CIs) were estimated through unconditional logistic regression models including terms for potential confounders.ResultsCompared to a low adherence to a cholesterol‐lowering diet (0–2 points), the ORs for a higher adherence (5–7 points) were 0.74 (95% CI: 0.60–0.92) for breast, 0.48 (95% CI: 0.30–0.77) for endometrial, and 0.77 (95% CI: 0.57–0.99) for ovarian cancer. The ORs for a 1‐point increment in the score were 0.87 (95% CI: 0.97–0.80), 0.80 (95% CI: 0.72–0.90), and 0.90 (95% CI: 0.84–0.97) for breast, endometrial, and ovarian cancers, respectively.ConclusionsA cholesterol‐lowering diet may favourably affect the risk of female hormone‐related cancers.

Understanding risk factors for endometrial cancer in young women

Abstract Background The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. Methods We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. Results In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet < .01). Body mass index was the strongest risk factor (OR≥35 vs<25 kg/m2 = 5.57, 95% CI = 4.33 to 7.16, for ages younger than 50 years; OR≥35 vs<25 kg/m2 = 4.68, 95% CI = 4.30 to 5.09, for ages 50 years and older; Phet = .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. Conclusions Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.

Risk prediction models for endometrial cancer: development and validation in an international consortium

Abstract Background Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. Methods We developed endometrial cancer risk prediction models using data on postmenopausal White women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in 3 cohorts: Nurses’ Health Study (NHS), NHS II, and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Results Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% confidence interval [CI] = 0.62 to 0.67) to 0.69 (95% CI = 0.66 to 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in area under the receiver operating characteristic curves in NHS; PLCO = 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall expected-to-observed ratio [E/O] = 1.09, 95% CI = 0.98 to 1.22) and PLCO (overall E/O = 1.04, 95% CI = 0.95 to 1.13) but poorly calibrated in NHS (overall E/O = 0.55, 95% CI = 0.51 to 0.59). Conclusions Using data from the largest, most heterogeneous study population to date (to our knowledge), prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.

Plant-Based Diets and Ovarian Cancer Risk

Objective: To assess the relationship between adherence to various plant-based diets, as measured by overall, healthy, and unhealthy plant-based diet indices (PDI, hPDI, uPDI), and ovarian cancer risk. Methods: We obtained data on 1031 cases of ovarian cancer and 2411 controls from a case-control study conducted in Italy. PDI, hPDI, and uPDI were calculated using data from a validated food frequency questionnaire. We used logistic regression to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) of ovarian cancer for PDI, hPDI, and uPDI, adjusting for several possible confounders. Results: PDI and hPDI were inversely related to ovarian cancer risk (OR = 0.70 for the fourth compared to the first quartile, 95% CI: 0.55–0.89, and OR = 0.67, 95% CI: 0.53–0.84, respectively). On the other hand, a higher uPDI was related to a higher risk of ovarian cancer (OR = 1.78, 95% CI: 1.40–2.28). The estimates for a 5-point increment in the indices were 0.88 (95% CI: 0.81–0.95) for PDI, 0.90 (95% CI: 0.83–0.96) for hPDI, and 1.15 (95% CI: 1.07–1.23) for uPDI. Consistent associations for the three indices were observed across strata of age, family history of breast/ovarian cancer, educational level, parity, oral contraceptives use, and menopausal status. Conclusions: Plant-based diets favorably influence ovarian cancer risk; plant-based diets characterized by a high intake of unhealthy plant foods are linked to an increased risk. Promoting diets rich in healthy plant foods could support the reduction of ovarian cancer risk.

Prevalence and indicators of cure of Italian women with vulvar squamous cell carcinoma: A population-based study

Five-year net survival and conditional survival from vulvar squamous cell carcinoma (VSCC) patients in Italy have shown no progress during the past three decades. This study aims to estimate the complete prevalence and multiple indicators of cure. Observed prevalence was estimated using 31 Italian cancer registries covering 47 % of Italian women. A subset of 22 cancer registries was used to estimate model-based long-term survival and indicators of cure, i.e., complete prevalence, cure fraction (CF), time to cure (TTC), proportion of 'already cured' patients, and cure prevalence. In 2018, VSCC patients alive in Italy (complete prevalence) were 6620 or 22 per 100,000 women. The cure fraction (the proportion of newly diagnosed patients who will not die of VSCC) did not change between 2000 and 2010 both for all patients (32 %) and in each age group. The time to cure (5-year conditional net survival >95 %) was 11 years for patients aged ≥44 years, but excess mortality remained for >15 years in the other age groups. This led to a negligible (5 %) proportion of 'already cured' patients (living longer than time to cure). The proportion of patients alive <2 years (21 %) was the same as that of patients surviving ≥15 years. The cure prevalence (patients who will not die of VSCC) was 64 %. A considerable proportion of patients will not be cured even among those who survived ≥5 years. There is an urgent need to reshape the current vulvar care model in Italy.

Indicators of cure for women living after uterine and ovarian cancers: a population-based study

Abstract This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate net survival, cure fraction, time to cure (when 5-year conditional net survival becomes &amp;gt; 95%), cure prevalence (women who will not die of cancer), and already cured (living longer than time to cure). In 2018, 0.4% (121 704) of Italian women were alive after diagnosis of corpus uteri cancer, 0.2% (52 551) after cervical cancer, and 0.2% (52 153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (cure prevalence). Women with gynecological cancers have a residual excess risk of death &amp;lt;5% at 5 years after diagnosis. The cure fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time to cure was ≤10 years for women with gynecological cancers aged &amp;lt;55 years; 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were already cured. These results can contribute to improving follow-up programs for women with gynecological cancers and supporting efforts against discrimination of already cured ones. This article is part of a Special Collection on Gynecological Cancers.

Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2)

Abstract Background: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. Methods: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. Results: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09–1.19). There was significant heterogeneity by study design (Phet &amp;lt; 0.01), with a stronger magnitude of association observed among case–control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. Conclusions: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. Impact: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.