Oral bisphosphonate use and colorectal cancer incidence in the Women's Health Initiative.

Bisphosphonates are widely prescribed to increase bone density in postmenopausal women with osteopenia or osteoporosis. Aminobisphosphonates have numerous anticancer properties and reduce bone metastases in cancer patients. Several studies, including the Women's Health Initiative (WHI), have found that use of oral bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies in women such as colorectal cancer (CRC). A few case-control and retrospective cohort studies have reported decreased risk of CRC among bisphosphonate users. In contrast, a prospective cohort study found no association. We evaluated the association between oral bisphosphonate use and CRC incidence in 156,826 postmenopausal women, ages 50 to 79 years, who participated in WHI clinical trials and observational study. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. A total of 1931 women were diagnosed with incident invasive CRC during a median follow-up of 12 years. Alendronate was the most commonly used bisphosphonate, accounting for >90% of the total person-years of use. The association between oral bisphosphonate use and CRC risk did not reach statistical significance (hazard ratio [HR] from multivariable-adjusted models = 0.88; 95% confidence interval [CI] 0.72-1.07; p = 0.19). Furthermore, we did not observe greater risk reductions for women with longer duration of use. Uncontrolled confounding may explain why previous studies have observed an association

Oral bisphosphonate use and colorectal cancer incidence in the Women's Health Initiative.

Bisphosphonates are widely prescribed to increase bone density in postmenopausal women with osteopenia or osteoporosis. Aminobisphosphonates have numerous anticancer properties and reduce bone metastases in cancer patients. Several studies, including the Women's Health Initiative (WHI), have found that use of oral bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies in women such as colorectal cancer (CRC). A few case-control and retrospective cohort studies have reported decreased risk of CRC among bisphosphonate users. In contrast, a prospective cohort study found no association. We evaluated the association between oral bisphosphonate use and CRC incidence in 156,826 postmenopausal women, ages 50 to 79 years, who participated in WHI clinical trials and observational study. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. A total of 1931 women were diagnosed with incident invasive CRC during a median follow-up of 12 years. Alendronate was the most commonly used bisphosphonate, accounting for >90% of the total person-years of use. The association between oral bisphosphonate use and CRC risk did not reach statistical significance (hazard ratio [HR] from multivariable-adjusted models = 0.88; 95% confidence interval [CI] 0.72-1.07; p = 0.19). Furthermore, we did not observe greater risk reductions for women with longer duration of use. Uncontrolled confounding may explain why previous studies have observed an association

Vitamin D intake and lung cancer risk in the Women's Health Initiative.

BackgroundPrior research suggests that vitamin D protects against lung cancer only among certain subgroups.ObjectivesWe investigated whether vitamin D intake was associated with lung cancer and explored whether vitamin A intake modified the association.DesignProspective cohort data from 128,779 postmenopausal women, including 1771 incident lung cancers in the Women's Health Initiative (Clinical Trials and Observational Study) 1993-2010, were analyzed. Twelve percent of women received active intervention (1 g Ca + 400 IU vitamin D3/d) in the Calcium/Vitamin D Trial. Baseline total intake included both dietary intake (from food-frequency questionnaires) and supplement intake (from bottle labels). HRs were estimated by Cox proportional hazard models.ResultsNo significant association was observed overall. Among never smokers, a total vitamin D intake ≥400 IU/d was significantly associated with lower risks of lung cancer (HR: 0.37; 95% CI: 0.18, 0.77 for ≥800 compared with <100 IU/d; P-trend = 0.01). No significant effect modification of total vitamin A intake on the association between total vitamin D intake and lung cancer was found. However, the Calcium/Vitamin D Trial active intervention was significantly associated with a lower lung cancer risk only among women with a vitamin A intake <1000 μg/d retinol activity equivalents (HR: 0.69; 95% CI: 0.50, 0.96; P-interaction = 0.09).ConclusionsVitamin D intake was associated with a lower lung cancer risk in never-smoking, postmenopausal women. Lower vitamin A intake may be important for a beneficial association of 1 g Ca + 400 IU vitamin D3 supplementation with lung cancer. This trial was registered at clinicaltrials.gov as NCT00000611

Serum 25-hydroxyvitamin D concentrations and lung cancer risk in never-smoking postmenopausal women

PurposeVitamin D has been implicated in lowering lung cancer risk, but serological data on the association among never-smoking women are limited. We report results examining the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with lung cancer risk among female never smokers. We also examined whether the association was modified by vitamin D supplementation and serum vitamin A concentrations.MethodsIn the Women's Health Initiative, including the calcium/vitamin D (CaD) Trial, we selected 298 incident cases [191 non-small cell lung cancer (NSCLC) including 170 adenocarcinoma] and 298 matched controls of never smokers. Baseline serum 25(OH)D was assayed by a chemiluminescent method. Logistic regression was used to estimate odds ratios (ORs) for quartiles and predefined clinical cutoffs of serum 25(OH)D concentrations.ResultsComparing quartiles 4 versus 1 of serum 25(OH)D concentrations, ORs were 1.06 [95% confidence interval (CI) 0.61-1.84] for all lung cancer, 0.94 (95% CI 0.52-1.69) for NSCLC, and 0.91 (95% CI 0.49-1.68) for adenocarcinoma. Comparing serum 25(OH)D ≥ 75 (high) versus <30 nmol/L (deficient), ORs were 0.76 (95% CI 0.31-1.84) for all lung cancer, 0.71 (95% CI 0.27-1.86) for NSCLC, and 0.81 (95% CI 0.31-2.14) for adenocarcinoma. There is suggestive evidence that CaD supplementation (1 g calcium + 400 IU D3/day) and a high level of circulating vitamin A may modify the associations of 25(OH)D with lung cancer overall and subtypes (p interaction <0.10).ConclusionsIn this group of never-smoking postmenopausal women, the results did not support the hypothesis of an association between serum 25(OH)D and lung cancer risk

Differences in Active and Passive Smoking Exposures and Lung Cancer Incidence Between Veterans and Non-Veterans in the Women's Health Initiative.

IntroductionWomen Veterans may have higher rates of both active and passive tobacco exposure than their civilian counterparts, thereby increasing their risk for lung cancer.Purpose of the studyTo compare differences in active and passive smoking exposure and lung cancer incidence among women Veterans and non-Veterans using prospective data from the Women's Health Initiative (WHI).Design and methodsWe used data from the WHI, which collected longitudinal demographic, clinical, and laboratory data on 161,808 postmenopausal women. We employed linear and multinomial regression and generalized linear models to compare active and passive smoking exposure between Veterans and non-Veterans and Cox proportional hazards models to estimate differences in lung cancer incidence rates.ResultsAfter adjustment, Veterans had 2.54 additional pack years of smoking compared with non-Veterans (95% confidence interval [CI] 1.68, 3.40). Veterans also had a 1% increase in risk of any passive smoking exposure (95% CI 1.00, 1.02) and a 9% increase in risk of any workplace exposure (95% CI 1.07, 1.11) compared with non-Veterans. After adjustment for age and smoking exposures, Veterans did not have a higher risk of lung cancer compared with non-Veterans (relative risk = 1.06 95% CI 0.86, 1.30).ImplicationsWomen Veterans had higher rates of tobacco use and exposure to passive smoking, which were associated with a higher risk for lung cancer compared with non-Veterans. Clinicians who care for Veterans need to be aware that older women Veterans have more exposures to risk factors for lung cancer

The Association of the C-Reactive Protein Inflammatory Biomarker with Breast Cancer Incidence and Mortality in the Women's Health Initiative.

Purpose: To examine associations of prediagnosis high-sensitivity C-reactive protein (hsCRP) with breast cancer incidence and postdiagnosis survival and to assess whether associations are modified by body mass index (BMI).Methods: A prospective analysis of the Women's Health Initiative was conducted among 17,841 cancer-free postmenopausal women with baseline hsCRP measurements. Cox proportional hazards models were used to examine associations between hsCRP concentrations and (i) breast cancer risk (n cases = 1,114) and (ii) all-cause mortality after breast cancer diagnosis. HRs are per 1 SD in log hsCRP.Results: hsCRP was not associated with breast cancer risk overall [HR = 1.05; 95% confidence interval (CI), 0.98-1.12]; however, an interaction between BMI and hsCRP was observed (Pinteraction = 0.02). A 1 SD increase in log hsCRP was associated with 17% increased breast cancer risk (HR = 1.17; 95% CI, 1.03-1.33) among lean women (BMI < 25), whereas no association was observed among overweight/obese (BMI ≥ 25) women. Prediagnosis hsCRP was not associated with overall mortality (HR, 1.04; 95% CI, 0.88-1.21) after breast cancer diagnosis; however, an increased mortality risk was apparent among leaner women with higher hsCRP levels (HR, 1.39, 95% CI, 1.03-1.88).Conclusions: Prediagnosis hsCRP levels are not associated with postmenopausal breast cancer incidence or survival overall; however, increased risks are suggested among leaner women. The observed effect modification is in the opposite direction of a previous case-control study finding and warrants further investigation.Impact: Associations of higher CRP levels with incident breast cancer and survival after breast cancer may depend on BMI. Cancer Epidemiol Biomarkers Prev; 26(7); 1100-6. ©2017 AACR

Intentional Weight Loss and Obesity-Related Cancer Risk

Background: Epidemiologic studies regarding weight loss and subsequent cancer risk are sparse. The study aim was to evaluate the association between weight change by intentionality and obesity-related cancer incidence in the Women's Health Initiative Observational Study. Eleven cancers were considered obesity related: breast, ovary, endometrium, colon and rectum, esophagus, kidney, liver, multiple myeloma, pancreas, stomach, and thyroid. Methods: Postmenopausal women (n = 58 667) aged 50-79 years had body weight and waist circumference (WC) measured at baseline and year 3. Weight or WC change was categorized as stable (change = 5%), and gain (>= 5%). Self-report at year 3 characterized weight loss as intentional or unintentional. During the subsequent 12 years (mean) of follow-up, 6033 incident obesity-related cancers were identified. Relationships were evaluated using multivariable Cox proportional hazards regression models. Results: Compared to women with stable weight, women with intentional weight loss had lower obesity-related cancer risk (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.80 to 0.98). A similar result was observed for intentional WC reduction (HR = 0.88, 95% CI = 0.80 to 0.96). Among all cancers, intentional weight loss was most strongly associated with endometrial cancer (HR = 0.61, 95% CI = 0.42 to 0.88). Intentional WC loss was also associated with lower colorectal cancer risk (HR = 0.79, 95% CI = 0.63 to 0.99). Unintentional weight loss or weight gain was not associated with overall obesity-related cancer risk. Conclusion: Intentional weight or WC loss in postmenopausal women was associated with lower risk of obesity-related cancer. These findings suggest that postmenopausal women who intentionally lose weight can reduce their obesity-related cancer risk.U.S. Department of Health and Human Services, National Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women

Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ≥30.0 kg/m2 ) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis