: Improved models for risk stratification can be useful for guiding public health strategies of breast cancer prevention. We combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors. Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. A model that included all risk factors provided a range of average absolute risk from 4.4%to 23.5%. Rising incidence rates of oropharyngeal cancers in numerous countries since the 1970s has been attributed to increased oral HPV exposure. However, the contribution of coincidental declines in the surgical removal of the palatine tonsils (i.e. tonsillectomy) is unknown. In Sweden, we quantified the association of tonsillectomy with other head and neck tumors. Tonsillectomies were associated with reduced risk of tonsil cancers, but unrelated to other oropharyngeal or other head and neck cancers. Prostate-specific antigen (PSA) testing has dramatically changed the composition of prostate cancer, making it difficult to assess incidence trends. By defining fatal prostate cancer as the underlying cause of death from disease within 10 years of diagnosis, we were able to conduct an in-depth analysis of clinically relevant prostate cancer incidence trends. In sum, fatal prostate cancer rates have substantially declined after widespread PSA screening and treatment advances. Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We used two unique population-based resources with molecular data to compare incidence rates for the intrinsic breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the US SEER database. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US. The benefits of breast cancer adjuvant systemic treatments are generally assumed to be proportional (or constant) over time, but limited data suggest that some treatment effects may vary with time. We systematically assessed the proportional hazards assumption across all 19 breast cancer adjuvant systemic therapy trials in the National Surgical Adjuvant Breast and Bowel Project (NSABP) database. Time-varying treatment effects were observed in nearly half of the trials (nine of 19). Accurate prognosis assessment after non-small cell lung cancer (NSCLC) diagnosis is the first essential step towards making effective clinical decisions. A simple and reliable prediction model with variables that are easy to obtain in routine clinical setting is highly warranted. This study aimed to develop a model to assess prognosis and predict mortality in patients with NSCLC in the U.S. Military Health System. Stepwise Cox regression identified age, sex, tobacco use, tumor stage, histology, surgery, chemotherapy, peripheral vascular disease, cerebrovascular disease and diabetes mellitus as significant predictors of survival among NSCLC patients. After external validation, the model can be translated into clinical use. Breast cancer began to decline in many Western countries during the late 1980s. We estimated the proportion of improvements in stage- and age-specific breast cancer survival in the United States explained by tumor size or estrogen receptor (ER) status. Hazards from breast cancerspecific death declined from 1973 to 2010, not only in the first 5 years after diagnosis, but also thereafter. Stratification by tumor size explained less than 17% of the improvements comparing 2005 to 2010 versus 1973 to 1979, except for women age 70 years with local (49%) or regional (38%) disease. Tumor size usually accounted for more of the improvement in the first 5 years after diagnosis than later. Additional adjustment for ER status (positive, negative, or unknown) from 1990 to 2010 did not explain much more of the improvement, except for women age 70years within 5 years after diagnosis. Most stage-specific survival improvement in women younger than age 70 years old was unexplained by tumor size and ER status, suggesting a key role for treatment. In the first 5 years after diagnosis, tumor size contributed importantly for women 70 years old with local and regional stage, and stratification by tumor size and ER status explained even more of the survival improvement among women age 70 years. No study has predicted the future incidence rate and annual burden (number) of new cases in the United States of invasive and in situ female breast cancers stratified by the estrogen receptor (ER) status. We constructed forecasts for women age 30 to 84 years in 2011 through 2030 using cancer incidence data from the Surveillance, Epidemiology, and End Results Program, novel age-period-cohort forecasting models, and population projections from the US Census Bureau. The total number of new tumors (invasive plus in situ) is expected to rise from 283 000 in 2011 to 441 000 in 2030. The proportion of all new case patients age 70 to 84 years is expected to increase from 24.3% to 34.8%, while the proportion ages 50 to 69 years is expected to decrease from 54.7% to 43.6%. The proportion of ER-positive invasive cancers is expected to remain nearly the same at 62.6%, whereas the proportion of ER-positive in situ cancers is expected to increase from 19.1% to 28.9%. The proportion of ER-negative cancers (invasive and in situ) is expected to decrease from 16.8% to 8.6%. Analyses of secular trends in incidence of inflammatory breast cancer, other non-inflammatory locally advanced breast cancers, and other breast cancers are underway for the period 1988-2012 (SEER). A study of risk of inflammatory breast cancer, other locally advanced non-inflammatory breast cancer, and other breast cancer in relationship to diabetes and components of the metabolic syndrome was undertaken using SEER-Medicare data. Obesity and diabetes were independently associated with increased risk of inflammatory breast cancer and other locally advanced breast cancer, but not of other breast cancer. Dyslipidemia was associated with reduced risk of inflammatory breast cancer and other locally advanced breast cancer, but not other forms of breast cancer. We implemented a novel method (medical condition-wide association study, MedWAS) to comprehensively evaluate medical risk factors for non-Hodgkin lymphoma (NHL), documented in administrative health claims. Fifty-five conditions were variously associated with NHL. Examples include well-established associations of HIV, solid organ transplantation, and hepatitis C virus with increased DLBCL risk, and autoimmune conditions with DLBCL and MZL. Risks for all NHL subtypes were increased after diagnoses of non-melanoma skin cancer, actinic keratosis, or hemolytic anemia. Nine additional skin conditions increased only TCL risk; Diabetes mellitus was associated with increased DLBCL risk. Associations varied significantly across NHL subtypes for 49 conditions 89%.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010183-14
Application #
9339165
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Davis Lynn, Brittny C; Rosenberg, Philip S; Anderson, William F et al. (2018) Black-White Breast Cancer Incidence Trends: Effects of Ethnicity. J Natl Cancer Inst :
Kelly, Scott P; Anderson, William F; Rosenberg, Philip S et al. (2018) Past, Current, and Future Incidence Rates and Burden of Metastatic Prostate Cancer in the United States. Eur Urol Focus 4:121-127
Mullooly, Maeve; Murphy, Jeanne; Gierach, Gretchen L et al. (2017) Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004-2013): Amassing data from independent Western populations provide etiologic clues. Eur J Cancer 86:326-333
Karami, Sara; Colt, Joanne S; Stewart, Patricia A et al. (2016) A case-control study of occupational sunlight exposure and renal cancer risk. Int J Cancer 138:1626-33
Sung, Hyuna; Rosenberg, Philip S; Chen, Wan-Qing et al. (2016) The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations. Int J Cancer 139:527-34
Rosenberg, Philip S; Barker, Kimberly A; Anderson, William F (2015) Future distribution of multiple myeloma in the United States by sex, age, and race/ethnicity. Blood 125:410-2
Richardson, Blakely S; Anderson, William F; Barnholtz-Sloan, Jill S et al. (2014) The age-specific effect modification of male sex for ulcerated cutaneous melanoma. JAMA Dermatol 150:522-5
Banegas, Matthew P; Tao, Li; Altekruse, Sean et al. (2014) Heterogeneity of breast cancer subtypes and survival among Hispanic women with invasive breast cancer in California. Breast Cancer Res Treat 144:625-34
Anderson, William F; Rosenberg, Philip S; Prat, Aleix et al. (2014) How many etiological subtypes of breast cancer: two, three, four, or more? J Natl Cancer Inst 106:
Daugherty, Sarah E; Lacey Jr, James V; Pfeiffer, Ruth M et al. (2013) Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH-AARP Diet and Health Study. Int J Cancer 133:462-72

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