Browsing by Author "Rohan, Thomas E."

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    Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence
    (Oxford University Press, 2025) Bea, Jennifer W.; Ochs-Balcom, Heather M.; Valencia, Celina I.; Chen, Zhao; Blew, Robert M.; Lind, Kimberly E.; Caan, Bette J.; Roe, Denise J.; Rohan, Thomas E.; Reeves, Katherine W.; Manson, JoAnn E.; Ballinger, Tarah; Reding, Kerryn W.; Follis, Shawna; Ziller, Shelby G.; Odegaard, Andrew O.; Medicine, School of Medicine
    Background: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear. Methods: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated. Dual-energy x-ray absorptiometry scans assessed adiposity at baseline, year 3, and year 6. Competing-risks multivariable sub-hazard ratios (SHR), with adjustments for sociodemographic, behavioral, reproductive, and anthropometric characteristics, were estimated for baseline and time-dependent associations between VAT, SAT, and incident BCa. Results: Participants averaged 63.3 ± 7.4 years of age and a BMI of 28.20 ± 5.72 kg/m2 at baseline. The models included 738 incident BCa case patients (N = 593 invasive; N = 145 in situ). Baseline VAT and SAT area were associated with statistically significantly increased BCa risk, by 36% and 19%, respectively. Increasing VAT/SAT ratio was associated with an 8% increase in incident BCa. Time-dependent models produced similar results. VAT and VAT/SAT associated BCa risk was highest for African American/Black women, although not statistically significantly different from other groups. Quartiles (Q) of VAT/SAT were also explored; the SHR for Q4 compared with Q1 was 1.49 (95% CI = 1.18 to 1.87). Conclusion: Higher abdominal VAT and SAT are associated with an increased risk of postmenopausal BCa, and VAT/SAT may provide a distinctive risk estimate. Potential racial and ethnic differences require replication in a larger sample.
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    Physical activity and risk of benign proliferative epithelial disorders of the breast, in the Women's Health Initiative
    (Oxford University Press, 2022) Peila, Rita; Chlebowski, Rowan T.; Ballinger, Tarah J.; Kamensky, Victor; Richey, Phyllis A.; Saquib, Nazmus; Shadyab, Aladdin H.; Wassertheil-Smoller, Sylvia; Rohan, Thomas E.; Medicine, School of Medicine
    Background: Recreational physical activity (PA) has been shown to be inversely associated with breast cancer risk. However, the association of recreational PA with benign proliferative epithelial disorders (BPED) of the breast, conditions associated with increased risk of breast cancer, has not been adequately studied. Methods: We used data from an ancillary study of benign breast disease conducted among the 68 132 postmenopausal women (aged 50-79 at recruitment) participating in the Women's Health Initiative randomized clinical trials. All clinical trial participants underwent annual or biennial mammogram screening. During the follow-up, for women who reported breast biopsies but were cancer free, the associated histological sections were obtained and subjected to standardized central pathology review. Self-reported recreational PA at baseline (n = 61 684) and at 3 years of the follow-up (n = 55 923) were quantified as metabolic equivalents [MET]-h/week. There were 1624 confirmed BPED cases during an average follow-up time of 7.7 years. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Higher average PA over 4 years was associated with lower risk of non-atypical BPED (P-trend = 0.02). There was a 6% lower risk of non-atypical BPED for every 5 MET-h/week increase between baseline and year 3 (HR = 0.94, 95% CI 0.89-0.99). Compared with women who remained inactive (PAbaseline and PAyear3 <9 MET-h/week), those who became active (PAbaseline<9 MET-h/week to PAyear3 ≥9 MET-h/weekee), remained active (PAbaseline and PAyear3 ≥9 MET-h/week), or decreased activity (PAbaseline ≥9 MET-h/week to PAyear3 <9 MET-h/week) had lower BPED risk. Conclusions: Recreational physical activity after menopause was associated with lower BPED risk among postmenopausal women.
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    Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative
    (Taylor & Francis, 2023) Ballinger, Tarah J.; Djuric, Zora; Sardesai, Sagar; Hovey, Kathleen M.; Andrews, Chris A.; Brasky, Theodore M.; Zhang, Jian Ting; Rohan, Thomas E.; Saquib, Nazmus; Shadyab, Aladdin H.; Simon, Michael; Wactawski-Wende, Jean; Wallace, Robert; Kato, Ikuko; Medicine, School of Medicine
    Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.