Browsing by Author "Desai, Manisha"

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    Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma
    (SpringerNature, 2016-08-19) Chahal, Harvind S.; Wu, Wenting; Ransohoff, Katherine J.; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A.; Li, Wen-Qing; Kraft, Peter; Hinds, David A.; Tang, Jean Y.; Han, Jiali; Sarin, Kavita Y.; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC.
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    Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer
    (AACR, 2018-06) Afghahi, Anosheh; Purington, Natasha; Han, Summer S.; Desai, Manisha; Pierson, Emma; Mathur, Maya B.; Seto, Tina; Thompson, Caroline A.; Rigdon, Joseph; Telli, Melinda L.; Badve, Sunil S.; Curtis, Christina N.; West, Robert B.; Horst, Kathleen; Gomez, Scarlett L.; Ford, James M.; Sledge, George W.; Kurian, Allison W.; Pathology and Laboratory Medicine, School of Medicine
    Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer–specific mortality (BCM) and overall mortality (OM) in TNBC. Experimental Design: Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts. Results: A total of 1,463 stage I–III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95% confidence interval (CI), 0.16–0.35] and BCM (HR = 0.19; CI, 0.11–0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (n = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy. Conclusions: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment.
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    Vitamin D levels and menopause-related symptoms.
    (Wolters Kluwer Health, 2014-11) LeBlanc, Erin S.; Desai, Manisha; Perrin, Nancy; Wactawski-Wende, Jean; Manson, JoAnn E.; Cauley, Jane A.; Michael, Yvonne L.; Tang, Jean; Womack, Catherine; Song, Yiqing; Johnson, Karen C.; O’Sullivan, Mary J.; Woods, Nancy; Stefanick, Marcia L.; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    Objective: To determine whether vitamin D levels are associated with menopause-related symptoms in older women. Methods: A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women’s Health Initiative Calcium and Vitamin D (CaD) trial of postmenopausal women aged 51-80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the CaD trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women [mean age 66.2 years (SD 6.8)] were included in these analyses. Results: There were borderline significant associations between 25(OH)D levels and total number of menopausal symptoms (p values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. There were no associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue (p’s > 0.10 for fully adjusted models). Conclusions: There was no evidence of a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.