Anna H. Wu

Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium

BACKGROUND Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. METHODS We analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. RESULTS Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100 mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500 mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). CONCLUSIONS Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

Background & Aims Barretts esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barretts and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. Methods We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. Results We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9). Conclusions We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Association between menopausal estrogen-only therapy and ovarian carcinoma risk

2 Alice W. Lee MPH, Roberta B. Ness MD, MPH, Lynda D. Roman MD, Kathryn L. Terry 3 ScD, Joellen M. Schildkraut PhD, Jenny Chang-Claude PhD, Jennifer A. Doherty PhD, 4 Usha Menon MD, Daniel W. Cramer MD, ScD, Simon A. Gayther PhD, Harvey Risch 5 MD, PhD, Aleksandra Gentry-Maharaj PhD, Marc T. Goodman PhD, Francesmary 6 Modugno PhD, Ursula Eilber, Kirsten B. Moysich PhD, Andrew Berchuck MD, Mary 7 Anne Rossing DVM, PhD, Allan Jensen PhD, Kristine G. Wicklund PhD, Kara L. 8 Cushing-Haugen MS, Estrid Hogdall PhD, DMSc, Anja Rudolph PhD, Pamela J. 9 Thompson MPH, Lynne R. Wilkens DrPH, Susanne K. Kjaer MD, DMSc, Michael E. 10 Carney MD, Daniel O. Stram PhD, Susan J. Ramus PhD, Anna H. Wu PhD, Malcolm C. 11 Pike PhD, Celeste Leigh Pearce PhD, MPH on behalf of the Ovarian Cancer Association 12

Cancer Epidemiology Among Asian Americans

Asian Americans are a diverse group and have a long history of migration to the United States (USA). Large differences in cancer rates between countries of origin and the USA, as well as diversity in lifestyle and environmental exposures, provide an opportunity to identify and study risk factors for specifi c cancers that can provide insights into cancer etiology and methods of prevention. The migration experience has created a type of natural experiment in which populations with a common genetic background have been exposed to different risk factors in a new environment and provides the opportunity to determine if risk factor changes can be linked to changes in their cancer rates. Multiple data sources are available to study cancer in Asian Americans, including US Census data to provide denominators for rates, cancer registries to assess cancer incidence, as well as observational studies in which personal risk factor information is obtained. Study designs which have been used include the ecologic, cross-sectional, case series, case-control, and cohort studies. Limitations and caveats in using these resources and study designs are described.

Body Weight, Menopausal Hormone Therapy, and Risk of Breast Cancer This work was supported by grant CA14089 from the National Cancer Institute and by grant BC044808 from the Department of Defense Congressionally Directed Breast Cancer Research Program.

Publisher Summary Two observations hold the key to understand the relationship of ovarian hormones to breast cancer risk as it applies to the treatment of postmenopausal women. Earlier menopause, whether natural or through bilateral oophorectomy, reduces breast cancer risk. The rate of breast cell proliferation in the luteal phase of the menstrual cycle is about double the rate in the follicular phase, and the rate in the follicular phase is considerably higher than in the postmenopausal period. This chapter uses these two observations to build a basic mathematical model of breast cancer etiology. This model gives an understanding of the quantitative effect of obesity on risk. The epidemiologic data, including that found in the Womens Health Initiative randomized trials on the quantitative effects of menopausal estrogen therapy and menopausal estrogen-progestin therapy on breast cancer risk is summarized. Its integration with the model provides a comprehensive understanding of the effect of estrogen and progestin treatment on breast cancer risk.Publisher Summary Two observations hold the key to understand the relationship of ovarian hormones to breast cancer risk as it applies to the treatment of postmenopausal women. Earlier menopause, whether natural or through bilateral oophorectomy, reduces breast cancer risk. The rate of breast cell proliferation in the luteal phase of the menstrual cycle is about double the rate in the follicular phase, and the rate in the follicular phase is considerably higher than in the postmenopausal period. This chapter uses these two observations to build a basic mathematical model of breast cancer etiology. This model gives an understanding of the quantitative effect of obesity on risk. The epidemiologic data, including that found in the Womens Health Initiative randomized trials on the quantitative effects of menopausal estrogen therapy and menopausal estrogen-progestin therapy on breast cancer risk is summarized. Its integration with the model provides a comprehensive understanding of the effect of estrogen and progestin treatment on breast cancer risk.