Decomposing the association of psychosocial wellbeing with all-cause mortality: the mediating role of physical health and lifestyle factors.

PURPOSE: This study quantified the effect of 48 psychosocial constructs on all-cause mortality using data from 7,698 individuals in the U.S. Health and Retirement Study. METHODS: Latent class analysis was used to divide participants into mutually exclusive psychosocial wellbeing groups (good, average, or poor) which was subsequently considered as the exposure. Mediation analysis was then conducted to determine the direct effect of the psychosocial wellbeing groups and the indirect (mediating) effects of physical health (functional status and comorbid conditions) and lifestyle factors (physical activity, smoking, and alcohol consumption) on overall survival. We also created a composite health index measure representing the summative effect of the mediators. RESULTS: We observed a strong and statistically significant total effect (TE) between survival time and psychosocial wellbeing group (survival time ratio (SR) = 1.73, 95% confidence interval (CI):1.50,2.01 when comparing good to poor). Mediation analysis revealed that the direct effect via psychosocial wellbeing group accounted for more than half of the TE (SR = 1.46, 95% CI:1.27,1.67). The composite health index measure mediated 36.2% of the TE with the natural indirect effect SR of 1.18 (95% CI:1.13,1.22). CONCLUSION: Our findings demonstrate the interconnectedness between psychosocial wellbeing and physical health and lifestyle factors on survival.

Estrogen Plus Progestin Hormone Therapy and Ovarian Cancer: A Complicated Relationship Explored.

BACKGROUND: Menopausal estrogen-alone therapy is a risk factor for endometrial and ovarian cancers. When a progestin is included with the estrogen daily (continuous estrogen-progestin combined therapy), there is no increased risk of endometrial cancer. However, the effect of continuous estrogen-progestin combined therapy on risk of ovarian cancer is less clear. METHODS: We pooled primary data from five population-based case-control studies in the Ovarian Cancer Association Consortium, including 1509 postmenopausal ovarian cancer cases and 2295 postmenopausal controls. Information on previous menopausal hormonal therapy use, as well as ovarian cancer risk factors, was collected using in-person interviews. Logistic regression was used to assess the association between use of continuous estrogen-progestin combined therapy and risk of ovarian cancer by duration and recency of use and disease histotype. RESULTS: Ever postmenopausal use of continuous estrogen-progestin combined therapy was not associated with increased risk of ovarian cancer overall (OR = 0.85, 95% CI = 0.72, 1.0). A decreased risk was observed for mucinous ovarian cancer (OR = 0.40, 95% CI = 0.18, 0.91). The other main ovarian cancer histotypes did not show an association (endometrioid: OR = 0.86, 95% CI = 0.57, 1.3, clear cell: OR = 0.68, 95% CI = 0.40, 1.2; serous: OR = 0.98, 95% CI = 0.80, 1.2). CONCLUSIONS: Given that estrogen-alone therapy has been shown to be associated with increased risk of ovarian cancer, these findings are consistent with the hypothesis that adding a progestin each day ameliorates the carcinogenic effects of estrogen on the cells of origin for all histotypes of ovarian cancer.

Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival.

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival. CONCLUSIONS: Pre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism.

"I am not a statistic" ovarian cancer survivors' views of factors that influenced their long-term survival.

OBJECTIVE: Although a high proportion of women with advanced stage ovarian cancer die within five years, approximately 30% will survive longer than this. The factors contributing to exceptional survival are currently poorly understood. The viewpoints of ovarian cancer survivors were qualitatively explored to determine the factors they felt have influenced their exceptional ovarian cancer survival. METHODS: Four focus groups, one each in Los Angeles (California), Ann Arbor (Michigan), New York (New York) and Edmonton (Alberta, Canada), were conducted with women who had survived at least five years. Physical activity, diet, meditation, prayer, treatment, complementary medicine, and side effects were explored in semi-structured discussions. The audiotaped sessions were transcribed and coded and then analyzed using Dedoose Version 8.0.35, a qualitative analysis software. RESULTS: Of the 26 women who participated, 23 had advanced stage disease. Three overarching themes emerged: (a) survivors had improved their 'lifestyles', including but not limited to fitness and diet; (b) survivors were able to draw on strong support systems, which included family, friends, support groups, faith communities, and healthcare workers; and (c) survivors had a strong life purpose, which manifested as positivity, taking charge of their lives, and advocating for themselves. CONCLUSIONS: Long-term survivors have varying experiences with their cancer, but identified lifestyle modification, motivation and persistence, strong life purpose, and strong support systems as key elements in their better survival. These preliminary findings indicate the need for further prospective studies to determine whether meaningful differences exist between short term and long term survivors on these characteristics.

Childhood diet and growth in boys in relation to timing of puberty and adult height: the Longitudinal Studies of Child Health and Development.

PURPOSE: To begin to explore the possible roles of childhood diet and growth in prostate cancer (PCa) development, we investigated these exposures in relation to two known/suspected PCa risk factors, earlier pubertal timing and greater attained height, in the Longitudinal Studies of Child Health and Development. METHODS: We used biannual/annual height, weight, and dietary history data to investigate childhood diet, body mass index (BMI), birth length, and childhood height in relation to PCa risk factors (age at peak height velocity (APHV), height at age 13, and adult height) for 64 Caucasian American boys. RESULTS: In adjusted models, childhood fat and animal protein intake was positively associated with height at age 13 and adult height (P < 0.05). A childhood diet high in fat and animal protein and low in vegetable protein was also associated with earlier APHV (P < 0.05), whereas no associations were observed for childhood energy intake or BMI. Birth length and childhood height were positively associated with height at age 13 and adult height, and childhood height was inversely associated with APHV (P < 0.05). CONCLUSION: Our findings suggest that both childhood diet and growth potential/growth contribute to earlier pubertal timing and taller attained height in males, supporting roles of these factors in PCa development.

Adiposity during early adulthood, changes in adiposity during adulthood, attained adiposity, and mammographic density among premenopausal women.

PURPOSE: We investigated the associations of adolescent adiposity, changes in adiposity during adulthood, and attained adiposity with volumetric mammographic density measures. METHODS: We recruited 383 premenopausal women who had a routine screening mammogram at the Breast Health Center, Washington University in St. Louis, MO from December 2015 to October 2016. Trained research personnel assessed current adiposity measures. Weight at ages 18 and 30 were self-reported. We evaluated mammographic density measures: volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV) using Volpara. Multivariable linear regression models were used to evaluate the associations of adiposity measures with volumetric mammographic density measures. RESULTS: All attained adiposity measures, BMI at age 18, age 30, and weight change were significantly inversely associated with VPD, and positively associated with DV and NDV. One unit increase in body fat % was associated with a 4.9% decrease in VPD and a 6.5% increase in NDV (p-values <0.001). For each kilogram increase in weight change from age 18 to attained, VPD decreased by 16.3%, 47.1%, and 58.8% for women who gained 5.1-15, 15.1-25 and >25 kg, respectively, compared to women who gained less than 5 kg during this time period (p-values <0.001). Irrespective of BMI at age 18, VPD significantly decreased and NDV increased among women who were currently obese. CONCLUSIONS: There is a need for mechanistic studies focusing on early adulthood to provide a better understanding of how adiposity in early life relates to mammographic density, and possibly breast cancer development in premenopausal women.

The association between China's Great famine and risk of breast cancer according to hormone receptor status: a hospital-based study.

PURPOSE: The Great Chinese Famine afflicted almost all Chinese people between 1959 and 1961. No study has explicitly assessed the association between an exposure to Chinese Famine and risk of overall breast cancer and tumor subtype. We evaluated the unique historical environmental influences of famine exposure on breast cancer subtypes. METHODS: 16,469 Chinese women who were diagnosed with invasive breast cancer in the Fudan University Shanghai Cancer Center (FUSCC) from 1999 to 2014 were analyzed. Four tumor subtypes were defined by both estrogen-receptor (ER) and progesterone-receptor (PR) status. Multinomial logistic regression models were used to estimate the odds ratios (ORs) of ER-PR-, ER+PR-, and ER-PR+ relative to ER+PR+ breast cancer for exposure to famine and age at the exposure. RESULTS: Compared with cases not exposed to the Famine, exposed cases were more likely to be diagnosed with ER-PR- (OR 1.60, 95 % CI 1.43-1.81), ER-PR+ (OR 4.85, 95 % CI 3.80-6.19), and ER+PR- (OR 1.99, 95 % CI 1.67-2.37) than ER+PR+ breast cancer after controlling for established breast cancer risk factors. Women exposed to Famine after first birth had a higher risk of EP-PR- (OR 1.66, 95 % CI 1.28-2.15), ER-PR+ (OR 9.75, 95 % CI 5.85-16.25), and ER+PR- (OR 2.35, 95 % CI 1.69-3.26) compared to those with ER+PR+ breast cancer. CONCLUSIONS: Women exposed to the Famine, particularly those exposed after first birth, were more likely to be diagnosed with ER-PR-, ER-PR+, and ER+PR- breast cancer. This retrospective analysis suggests that famine, malnutrition, or the associated lack of fruit and vegetable consumption in adulthood may be related to epidemiological heterogeneity within breast cancer subtypes.

Reproductive Factors Do Not Influence Survival with Ovarian Cancer.

BACKGROUND: Previous studies on the association between reproductive factors and ovarian cancer survival are equivocal, possibly due to small sample sizes. METHODS: Using data on 11,175 people diagnosed with primary invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer (ovarian cancer) from 16 studies in the Ovarian Cancer Association Consortium (OCAC), we examined the associations between survival and age at menarche, combined oral contraceptive use, parity, breastfeeding, age at last pregnancy, and menopausal status using Cox proportional hazard models. The models were adjusted for age at diagnosis, race/ethnicity, education level, and OCAC study and stratified on stage and histotype. RESULTS: During the mean follow-up of 6.34 years (SD = 4.80), 6,418 patients passed away (57.4%). There was no evidence of associations between the reproductive factors and survival among patients with ovarian cancer overall or by histotype. CONCLUSIONS: This study found no association between reproductive factors and survival after an ovarian cancer diagnosis. IMPACT: Reproductive factors are well-established risk factors for ovarian cancer, but they are not associated with survival after a diagnosis of ovarian cancer.

Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies.

BACKGROUND: Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. METHODS: A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. RESULTS: Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. CONCLUSIONS: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women.

Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women. At the time of mammogram, the mean age was 57.9 years. Compared with women who had a BMI gain of 0.1-5 kg/m2 from age 10, women who had a BMI gain of 5.1-10 kg/m2 had a 24.4% decrease [95% confidence interval (CI), 6.0%-39.2%] in volumetric percent density; women who had a BMI gain of 10.1-15 kg/m2 had a 46.1% decrease (95% CI, 33.0%-56.7%) in volumetric percent density; and women who had a BMI gain of >15 kg/m2 had a 56.5% decrease (95% CI, 46.0%-65.0%) in volumetric percent density. Similar, but slightly attenuated associations were observed for BMI gain from ages 18 and 30 to age at mammogram and volumetric percent density. BMI gain over the life course was positively associated with nondense volume, but not dense volume. We observed strong associations between BMI change over the life course and mammographic breast density. The inverse associations between early-life adiposity change and volumetric percent density suggest that childhood adiposity may confer long-term protection against postmenopausal breast cancer via its effect of mammographic breast density.

Association Between Life Purpose and Mortality Among US Adults Older Than 50 Years.

Importance: A growing body of literature suggests that having a strong sense of purpose in life leads to improvements in both physical and mental health and enhances overall quality of life. There are interventions available to influence life purpose; thus, understanding the association of life purpose with mortality is critical. Objective: To evaluate whether an association exists between life purpose and all-cause or cause-specific mortality among older adults in the United States. Design, Setting, and Participants: The Health and Retirement Study (HRS) is a national cohort study of US adults older than 50 years. Adults between the ages of 51 to 61 were enrolled in the HRS, and their spouses or partners were enrolled regardless of age. Initially, individuals born between 1931 and 1941 were enrolled starting in 1992, but subsequent cohort enrichment was carried out. The present prospective cohort study sample was drawn from 8419 HRS participants who were older than 50 years and who had filled out a psychological questionnaire during the HRS 2006 interview period. Of these, 1142 nonresponders with incomplete life purpose data, 163 respondents with missing sample weights, 81 participants lost to follow-up, 1 participant with an incorrect survival time, and 47 participants with missing information on covariates were excluded. The final sample for analysis was 6985 individuals. Data analyses were conducted between June 5, 2018, and April 22, 2019. Exposures: Purpose in life was assessed for the 2006 interview period with a 7-item questionnaire from the modified Ryff and Keyes Scales of Psychological Well-being evaluation using a Likert scale ranging from 1 to 6, with higher scores indicating greater purpose in life; for all-cause and cause-specific mortality analyses, 5 categories of life purpose scores were used (1.00-2.99, 3.00-3.99, 4.00-4.99, 5.00-5.99, and 6.00). Main Outcomes and Measures: All-cause and cause-specific mortality were assessed between 2006 and 2010. Weighted Cox proportional hazards models were used to evaluate life purpose and mortality. Results: Of 6985 individuals included in the analysis, 4016 (57.5%) were women, the mean (SD) age of all participants was 68.6 (9.8) years, and the mean (SD) survival time for decedents was 31.21 (15.42) months (range, 1.00-71.00 months). Life purpose was significantly associated with all-cause mortality in the HRS (hazard ratio, 2.43; 95% CI, 1.57-3.75, comparing those in the lowest life purpose category with those in the highest life purpose category). Some significant cause-specific mortality associations with life purpose were also observed (heart, circulatory, and blood conditions: hazard ratio, 2.66; 95% CI, 1.62-4.38). Conclusions and Relevance: This study's results indicated that stronger purpose in life was associated with decreased mortality. Purposeful living may have health benefits. Future research should focus on evaluating the association of life purpose interventions with health outcomes, including mortality. In addition, understanding potential biological mechanisms through which life purpose may influence health outcomes would be valuable.

Adiposity at Age 10 and Mammographic Density among Premenopausal Women.

Although childhood adiposity is inversely associated with breast cancer risk, the association of childhood adiposity with mammographic density in premenopausal women has not been adequately studied. We analyzed data from 365 premenopausal women who came in for screening mammography at Washington University (St. Louis, MO) from 2015 to 2016. Body size at age 10 was self-reported using somatotype pictogram. Body mass index (BMI) at age 10 was imputed using data from Growing Up Today Study. Volpara software was used to evaluate volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). Adjusted multivariable linear regression models were used to evaluate the associations between adiposity at age 10 and mammographic density measures. Adiposity at age 10 was inversely associated with VPD and positively associated with NDV. A 1 kg/m2 increase in BMI at age 10 was associated with a 6.4% decrease in VPD, and a 6.9% increase in NDV (P < 0.001). Compared with women whose age 10 body size was 1 or 2, women with body size 3 or 4 had a 16.8% decrease in VPD and a 26.6% increase in NDV, women with body size 5 had a 32.2% decrease in VPD and a 58.5% increase in NDV, and women with body sizes ≥6 had a 47.8% decrease in VPD and a 80.9% increase in NDV (P < 0.05). The associations were attenuated, but still significant after adjusting for current BMI. Mechanistic studies to understand how childhood adiposity influences breast development, mammographic density, and breast cancer in premenopausal women are needed. Cancer Prev Res; 11(5); 287-94. ©2018 AACR.