Weight loss randomized intervention trials in female cancer survivors

Purpos

Estrogen and progesterone-related gene variants and colorectal cancer risk in women

<p>Abstract</p> <p>Background</p> <p>Observational studies and randomized trials have suggested that estrogens and/or progesterone may lower the risk for colorectal cancer. Inherited variation in the sex-hormone genes may be one mechanism by which sex hormones affect colorectal cancer, although data are limited.</p> <p>Method</p> <p>We conducted a comprehensive evaluation of single nucleotide polymorphisms (SNPs) in genes encoding 3 hormone receptors (<it>ESR1, ESR2, PGR</it>) and 5 hormone synthesizers (<it>CYP19A1 and CYP17A1, HSD17B1, HSD17B2, HSD17B4</it>) among 427 women with incident colorectal cancer and 871 matched controls who were Caucasians of European ancestry from 93676 postmenopausal women enrolled in the Women's Health Initiative Observational cohort. A total of 242 haplotype-tagging and functional SNPs in the 8 genes were included for analysis. Unconditional logistic regression with adjustment for age and hysterectomy status was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).</p> <p>Results</p> <p>We observed a weak association between the <it>CYP17A1 </it>rs17724534 SNP and colorectal cancer risk (OR per risk allele (A) = 1.39, 95% CI = 1.09-1.78, corrected p-value = 0.07). In addition, a suggestive interaction between rs17724534 and rs10883782 in 2 discrete LD blocks of <it>CYP17A1 </it>was observed in relation to colorectal cancer (empirical p value = 0.04). Moreover, one haplotype block of <it>CYP19A1 </it>was associated with colorectal cancer (corrected global p value = 0.02), which likely reflected the association with the tagging SNP, rs1902584, in the block.</p> <p>Conclusion</p> <p>Our findings offer some support for a suggestive association of <it>CYP17A1 </it>and <it>CYP19A1 </it>variants with colorectal cancer risk.</p

Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women’s Health Initiative clinical trial and observational study

Background: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women’s Health Initiative (WHI) estrogen plus progestin randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants and Methods: Postmenopausal women aged 50-79 at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were post-hysterectomy from the observational study and clinical trial respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review. Results: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53 to 1.20) for estrogen and 1.15 (0.74 to 1.79) for estrogen plus progestin, with respectively 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period. Conclusion: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7-8 years of treatment and follow-up

The Aromatase Gene (CYP19A1) Variants and Circulating Hepatocyte Growth Factor in Postmenopausal Women

Background: Estrogen and androgen have been linked to the regulation of circulating hepatocyte growth factor (HGF), an adipose tissue-derived cytokine. It is possible that the CYP19A1 gene which alters sex hormones production may influence HGF levels. We examined the association between the CYP19A1 gene variants and plasma HGF concentrations. Design We evaluated 45 common and putative functional variants of CYP19A1 and circulating levels of HGF among 260 postmenopausal women who later developed colorectal cancer from the Women's Health Initiative Observational Cohort. As the distribution of HGF levels was highly skewed, we transformed HGF concentrations for all women into a log-, ranked-, or normal score-scale value. Multiple linear regression with adjustment for age was used to evaluate the associations. Results: We observed an association between the rs7172156, rs1008805, rs6493494, rs749292, and rs11636639 variants and HGF levels in ranked and normal score scales (corrected p values ≤0.02), although the association of these 5 SNPs with log-scale HGF was not significant (corrected p values ≥0.16). The associations remained unchanged after additional adjustment for hormone therapy use and estradiol levels. These 5 SNPs, which were in linkage disequilibrium (pairwise D′≥97%, r2≥56%), constituted a block with 2 common haplotypes accounting for 82% frequency. The most common haplotype, TCCCA, was associated with lower ranked- or normal score-transformed HGF levels (corrected p values ≤0.001), whereas the second most common haplotype, CTTCA, was associated with higher ranked- or normal score-transformed HGF levels (corrected p values ≤0.02). Conclusion: Our findings of a potential association between the CYP19A1 variants and circulating HGF levels warrant confirmation in studies with larger sample size

Frequency of Private Spiritual Activity and Cardiovascular Risk in Post-menopausal Women: The Women\u27s Health Initiative

Purpose: Spirituality has been associated with better cardiac autonomic balance, but its association with cardiovascular risk is not well studied. We examined whether more frequent private spiritual activity was associated with reduced cardiovascular risk in postmenopausal women enrolled in the Women’s Health Initiative Observational Study. Methods: Frequency of private spiritual activity (prayer, Bible reading, and meditation) was selfreported at year 5 of follow-up. Cardiovascular outcomes were centrally adjudicated, and cardiovascular risk was estimated from proportional hazards models. Results: Final models included 43,708 women (mean age: 68.9±7.3; median follow-up: 7.0 years) free of cardiac disease through year 5 of follow-up. In age-adjusted models private spiritual activity was associated with increased cardiovascular risk (HR: 1.16; CI 1.02, 1.31, weekly vs. never; 1.25; CI 1.11, 1.40, daily vs. never). In multivariate models adjusted for demographics, lifestyle, risk factors, and psychosocial factors, such association remained significant only in the group with daily activity (HR 1.16; CI: 1.03, 1.30). Subgroup analyses indicate this association may be driven by the presence of severe chronic diseases. Conclusion: In aging women, higher frequency of private spiritual activity was associated with increased cardiovascular risk, likely reflecting a mobilization of spiritual resources in order to cope with aging and illness

Post-diagnosis body mass index and mortality among women diagnosed with endometrial cancer: Results from the Women\u27s Health Initiative.

Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women\u27s Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55-1.91). Our study does not support the hypothesis that higher BMI after endometrial cancer diagnosis is associated with poorer survival

Genetic variants in the MRPS30 region and postmenopausal breast cancer risk

Abstract{no abstract

Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects

Introduction: Paradoxically, a breast cancer risk reduction with conjugated equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone acetate (CEE + MPA) were observed in the Women’s Health Initiative (WHI) randomized controlled trials. The effects of hormone therapy on serum sex hormone levels, and on the association between baseline sex hormones and disease risk, may help explain these divergent breast cancer findings. Methods: Serum sex hormone concentrations were measured for 348 breast cancer cases in the CEE + MPA trial and for 235 cases in the CEE trial along with corresponding pair-matched controls, nested within the WHI trials of healthy postmenopausal women. Association and mediation analyses, to examine the extent to which sex hormone levels and changes can explain the breast cancer findings, were conducted using logistic regression. Results: Following CEE treatment, breast cancer risk was associated with higher concentrations of baseline serum estrogens, and with lower concentrations of sex hormone binding globulin. However, following CEE + MPA, there was no association of breast cancer risk with baseline sex hormone levels. The sex hormone changes from baseline to year 1 provided an explanation for much of the reduced breast cancer risk with CEE. Specifically, the treatment odds ratio (95% confidence interval) increased from 0.71 (0.43, 1.15) to 0.92 (0.41, 2.09) when the year 1 measures were included in the logistic regression analysis. In comparison, the CEE + MPA odds ratio was essentially unchanged when these year 1 measures were included. Conclusions: Breast cancer risk remains low following CEE use among women having favorable baseline sex hormone profiles, but CEE + MPA evidently produces a breast cancer risk for all women similar to that for women having an unfavorable baseline sex hormone profile. These patterns could reflect breast ductal epithelial cell stimulation by CEE + MPA that is substantially avoided with CEE, in conjunction with relatively more favorable effects of either regimen following a sustained period of estrogen deprivation. These findings may have implications for other hormone therapy formulations and routes of delivery. Trial registration clinicaltrials.gov identifier: NCT00000611

Racial and Ethnic Variations in Lung Cancer Incidence and Mortality: Results From the Women’s Health Initiative

This study aimed to evaluate racial/ethnic differences in lung cancer incidence and mortality in the Women’s Health Initiative Study, a longitudinal prospective cohort evaluation of postmenopausal women recruited from 40 clinical centers