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We propose a novel statistical framework by supplementing case-control data with summary statistics on the population at risk for a subset of risk factors. Our approach is to first form two unbiased estimating equations, one based on the case-control data and the other on both the case data and the summary statistics, and then optimally combine them to derive another estimating equation to be used for the estimation. The proposed method is computationally simple and more efficient than standard approaches based on case-control data alone. We also establish asymptotic properties of the resulting estimator, and investigate its finite-sample performance through simulation. As a substantive application, we apply the proposed method to investigate risk factors for endometrial cancer, by using data from a recently completed population-based case-control study and summary statistics from the Behavioral Risk Factor Surveillance System, the Population Estimates Program of the US Census Bureau, and the Connecticut Department of Transportation., (© 2014, The International Biometric Society.)

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

Exposure to electromagnetic fields (EMFs) from use of electric blankets and other in-home electrical appliances has been hypothesized to increase breast cancer risk. To test the hypothesis, the authors analyzed data from a case-control study of female breast cancer conducted in Connecticut in 1994–1997. A total of 608 incident breast cancer patients and 609 age frequency-matched controls, 31–85 years old, were interviewed by trained study interviewers using a standardized, structured questionnaire to obtain information on lifetime use of various in-home electrical appliances. A total of 40% of the cases and 43% of the controls reported regular use of electric blankets in their lifetime, which gave an adjusted odds ratio of 0.9 (95% confidence interval (Cl): 0.7, 1.1). For those who reported using electric blankets continuously throughout the night, the adjusted odds ratio was 0.9 (95% Cl: 0.7, 1.2) when compared with never users. The risk did not vary according to age at first use, duration of use, or menopausal and estrogen receptor status. The authors also did not find an association between use of other major in-home electrical appliances and breast cancer risk. In conclusion, exposure to EMFs from in-home electrical appliance use was not found to increase breast cancer risk in this study. Am J Epidemiol 2000; 151: 1103-11. [ABSTRACT FROM PUBLISHER]

Several recent studies have suggested a potential role of menstrual and reproductive factors in the risk of non-Hodgkin’s lymphoma. To further examine the relation, the authors analyzed data from a population-based case-control study of non-Hodgkin’s lymphoma in Connecticut women between 1996 and 2000. A total of 601 histologically confirmed cases and 717 randomly selected population-based controls were included in this study. An in-person interview was conducted using a standardized and structured questionnaire to collect information on menstrual and reproductive factors and potential confounding factors. Compared with nulliparous women, women who had four or more pregnancies during their lifetime were found to have a significantly reduced risk of non-Hodgkin’s lymphoma (odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.4, 0.9). Risk appeared to decrease with increasing number of pregnancies (ptrend = 0.03). The authors also observed an increased risk of non-Hodgkin’s lymphoma overall (OR = 1.5, 95% CI: 1.0, 2.2) and of diffuse non-Hodgkin’s lymphoma (OR = 1.7, 95% CI: 1.1, 2.7) for women who started their first menstrual period at age 15 or more years compared with those who started their first menstrual period before age 12 years. These findings support a reduced risk of non-Hodgkin’s lymphoma associated with multiple pregnancies and an increased risk of non-Hodgkin’s lymphoma associated with later age at menarche. [ABSTRACT FROM AUTHOR]

A population-based case-control study (601 cases and 717 controls) was conducted in 1995–2001 among Connecticut women to evaluate the relation between diet and nutrient intakes and the risk of non-Hodgkin’s lymphoma (NHL). When the highest quartile of intake was compared with the lowest, the authors found an increased risk of NHL associated with animal protein (odds ratio = 1.7, 95% confidence interval: 1.2, 2.4) and saturated fat (odds ratio = 1.9, 95% confidence interval: 1.1, 2.3) but a reduced risk for polyunsaturated fat (odds ratio = 0.6, 95% confidence interval: 0.4, 0.9) and no relation for vegetable protein and monounsaturated fat. An increased risk was also observed for higher intakes of retinol, eggs, and dairy products. On the other hand, a reduced risk was found for higher intakes of dietary fiber and for several fruit and vegetable items. Risk of NHL associated with diet and nutrient intakes appeared to vary based on NHL subtype. An association between dietary intake and NHL risk is biologically plausible because diets high in protein and fat may lead to altered immunocompetence, resulting in an increased risk of NHL. The antioxidant or inhibiting nitrosation reaction properties of vegetables and fruits may result in a reduced risk. Further investigation of the role of dietary intakes on the risk of NHL is warranted. [ABSTRACT FROM AUTHOR]

Experimental studies show that hormonal and nonhormonal activities of polychlorinated biphenyls (PCBs) are structure dependent, suggesting that the breast cancer risk associated with PCBs may vary according to specific PCB congeners. In 1994–1997, the authors conducted a case-control study of Connecticut women to investigate whether breast cancer risk is associated with body burden of PCBs and varies by PCB congeners. A total of 304 breast cancer cases and 186 controls aged 40–79 years were recruited into the study. Fresh breast adipose tissue was analyzed for PCBs. The age- and lipid-adjusted geometric mean tissue levels of total PCBs were not significantly different (p = 0.46) for the cases (478.6 parts per billion) and controls (494.1 parts per billion). The covariate-adjusted odds ratio was 0.7 (95% confidence interval: 0.4, 1.1) for all study participants when the third tertile was compared with the lowest tertile. No individual congeners or groups of congeners were associated with a significantly increased risk of breast cancer. Further stratification by type of breast disease; menopausal, parity, and lactation status; and body size also showed no significant association with body levels of PCBs. These results suggest that environmental exposure to PCBs may not substantially affect breast cancer risk. [ABSTRACT FROM PUBLISHER]