Research Findings

Pooled Studies using USRT data

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project (2018)
 In a pooled analysis of 1.52 million adults from 14 U.S. cohort studies, increased risks for both hepatocellular carcinoma (HCC; 1,423 cases) and intrahepatic cholangiocarcinoma (ICC; 410 cases) were associated with cigarette smoking and heavy alcohol consumption at baseline. Smoking cessation and light-to-moderate drinking were associated with reduced risk for HCC but not ICC.
Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis (2018)
 Based on a pooled analsis of 1.54 million individuals from 13 prospective studies, risk for intrahepatic cholangiocarcima (n=414 cases) was 62% higher in the obese and 81% greater in those with a history of diabetes. Similar findings were observed in a separate meta-analysis of 14 studies identified through a systematic review of the literature.
Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women (2018)
 In a pooled analysis of individual data for 758,592 premenopausal women from 19 international cohort studies, risk for premenopausal breast cancer (13,082 cases) decreased significantly with increasing body mass index (BMI) at ages 18-24, 25-34, 35-44, and 45-54. The inverse association was stronger for BMI at younger versus older ages and for hormone receptor-positive versus hormone receptor-negative tumors, but did not differ substantially by attained age or with adjustment for other breast cancer risk factors.
Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies (2017)
 In a pooled analysis of 1.9 million individuals from 19 U.S. and European cohort studies, gallbladder cancer (n=567 cases) risk increased significantly with increasing measures of adult BMI, young adult BMI, adult weight gain, height, waist circumference, and waist-height ratio, but was not associated with waist-hip ratio. Findings did not differ appreciably by sex or other demographic/lifestyle factors.
The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium (2017)
 The Premenopausal Breast Cancer Collaborative Group was created to evaluate risk factors for premenopausal breast cancer by pooling data from 20 U.S. cohort studies participating in the National Cancer Institute Cohort Consortium. This article describes the individual cohorts and study objectives.
Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for U.S. Adults (2016)
 In a pooled analysis of 1.57 million adults from 14 U.S. cohort studies, liver cancer (n=2,162 cases) risk was associated with greater BMI, greater waist circumference, and history of diabetes, although the BMI association was limited to those who were sera-negative for hepatitis.
Anthropometric factors and thyroid cancer risk by histological subtype: pooled analysis of 22 prospective studies (2016)
 A pooled analysis of 22 prospective studies revealed increased thyroid cancer incidence and mortality risks with height, waist circumference, young adult BMI, and adulthood weight gain.
Association of leisure-time physical activity and risk of 26 types of cancer in 1.44 million adults (2016)
 A pooled analysis of 1.44 million individuals from 12 U.S. and European cohort studies identified decreased risks of 13 different cancers in individuals with high compared to low levels of leisure-time physical activity. Risks were generally similar for overweight/obese and normal-weight individuals.
Body-mass index and all-cause mortality: individual participant-data meta-analysis of 239 prospective studies in four continents (2016)
 In a pooled analysis of 10.6 million people from 239 prospective studies in Asia, Australia/New Zealand, Europe, and North America, all-cause mortality increased with increasing BMI, and risks were consistent across all four continents.
Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus (2016)
 In a pooled analysis of breast cancer cases (63,337) and comparison subjects from 96 international studies participating in the Breast Cancer Association Consortium and the Consortium of Investigators of Modifiers, fine-scale mapping of a locus on chromosome 12 (12p11) identified four independent association signals for breast cancer risk among women of European origin. Multiple candidate causal variants were identified at each signal and several putative functional variants were also identified.
Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship (2015)
 In a pooled analysis of 6 prospective cohorts, individuals who reported 1-5 times the recommended minimum leisure time physical activity of 7.5 metabolic-equivalent hours per week experienced 31-39% lower mortality from all causes, and similar reductions in mortality from cardiovascular disease and cancer, compared to those with no leisure time physical activity.
Anthropometry and head and neck cancer: a pooled analysis of cohort data (2015)
 A pooled analysis of 20 cohort studies reported that mortality from head and neck cancer was increased with greater waist circumference and waist-to-hip ratio after adjustment for BMI; risk was also related to BMI, but only in non-smokers.
Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies (2015)
 In a pooled analysis of 20 cohort studies, pancreatic mortality risk was elevated with higher waist circumference and waist-to-hip ratio after adjustment for BMI, and was higher in individuals who were overweight or obese compared to normal weight in early adulthood.
Prediction of breast cancer risk based on profiling with common genetic variants (2015)
 Genomic profiling based on 77 currently established single nucleotide polymorphisms was found to improve breast cancer risk prediction in women with and without a family history of breast cancer.
Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project (2015)
 In a pooled analysis of 11 prospective cohorts, liver cancer risk was elevated in women who had bilateral-oophorectomy, but was not associated with oral contraceptive use, parity, age at first birth, age at natural menopause, or duration of fertility.
Thyroid cancer and nonsteroidal anti-inflammatory drug use: A pooled analysis of patients over 40 years of age (2015)
 A pooled analysis of 3 prospective cohorts revealed that thyroid cancer risk was not associated with aspirin or non-aspirin NSAID use; risk was increased in women and with obesity, and reduced with smoking and alcohol consumption.
Coffee consumption and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma by sex: The Liver Cancer Pooling Project (2015)
 A pooled study of 11 cohorts reported a decreased risk for hepatocellular carcinoma with increased coffee consumption, especially in women, but no association for intrahepatic cholangiocarcinoma with coffee consumption.
NSAID use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project (2015)
 In a pooled analysis of 10 cohort studies, hepatocellular carcinoma risk was reduced with current aspirin use, but not associated with Ibuprofen use.
Analysis of heritability and shared heritability based on genome-wide association studies for thirteen cancer types (2015)
 Findings from an analysis of more than 80,000 individuals revealed a large heritable component to most cancers, but most of the cancer heritability could not be attributed to known susceptibility loci, marker SNPs were not consistently present across cancers, and genetic correlations between most pairs of cancer sites were not strong.
Association between class III obesity (BMI of 40-59 kg/m2) and mortality: A pooled analysis of 20 prospective studies (2014)
 In a pooled analysis of 313,575 participants from 20 prospective cohort studies, including 22,872 radiologic technologists, individuals with Class III obesity (BMI=40.0-59.9) had substantially higher risks for mortality from all causes, heart, cancer, cerebrovascular, diabetes and other diseases than their normal weight (BMI=18.5-24.9) counterparts.
Body size and multiple myeloma mortality: A pooled analysis of 20 prospective studies (2014)
 In a pooled analysis of over 1.5 million participants from 20 prospective cohort studies, including 82,346 radiologic technologists, risk for mortality from multiple myeloma was increased with increasing BMI at baseline, BMI at study entry, and central adiposity (waist circumference), but was not associated with waist-to-hip ratio.
Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer (2013)
 In a pooled case-control study of 344 PTC cases and 452 controls, associations were examined between papillary thyroid cancer (PTC) risk and 3,985 tag single nucleotide polymorphisms (SNPs) in 240 candidate gene regions involved in immune function pathways. Two SNPs in the SERPINA5 gene were significantly associated with PTC risk, independent of a history of autoimmune thyroiditis, and the strong association with SERPINA5 largely explained the significantly increased risk of PTC with the combined group of SNPs in the complement and coagulation cascade pathway.
Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors (2013)
 Using data from 24 studies participating in the Breast Cancer Association Consortium, including 34,793 breast cancer cases and 41,099 controls of European ancestry, the authors examined whether risks associated with 23 single nucleotide polymorphisms (SNPs) were modified by 10 established breast cancer risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity). Risks associated with two SNPs varied by parity status and risk related to one SNP varied by alcohol consumption.
An aggregated analysis of hormonal factors and endometrial cancer risk by parity (2013)
 In a pooled analysis of 173,519 postmenopausal women from four prospective studies, risks for endometrial cancer with established hormone-related risk factors (age at menarche, age at menopause, body mass index, oral contraceptives, menopausal hormone therapy) were examined by parity status. Endometrial cancer risks associated with these factors did not vary significantly between parous (1,378 cases) and nulliparous (360 cases) women.
Common genetic variants in metabolism and detoxification pathways and the risk of papillary thyroid cancer (2012)
 Associations between papillary thyroid cancer (PTC) risk and 1647 tagging single nucleotide polymorphisms (SNPs) in 132 candidate genes/regions involved in metabolism and detoxification pathways were examined in a pooled case-control study of 344 PTC cases and 452 controls. Several observed associations between PTC risk with SNPs and genes/regions were observed but none remained significant after adjustment for multiple comparisons; however, significant interactions were observed between the UGT2B7 and NAT1 genes and alcohol intake and between the CYP26B1 gene and tobacco intake, suggesting that alcohol or tobacco intake may modify gene-related risks of PTC.
Ovarian cancer and smoking: individual participant meta-analysis including 28,114 women with ovarian cancer from 51 epidemiological studies (2012)
 A meta-analysis based on 28,114 women with ovarian cancer from 51 epidemiological studies revealed that smoking-related risk differed by ovarian cancer cell type. Risk for mucinous ovarian cancer was significantly higher in current vs. never smokers, particularly among those with borderline malignant tumors, while risks for endometrial and clear-cell ovarian cancers were significantly reduced in current vs. never smokers. Smoking was not associated with risk for serous ovarian cancer.
Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies (2012)
 In a meta-analysis that included 25,157 women with ovarian cancer from 47 epidemiological studies, ovarian cancer risk increased significantly with increasing height, weight, and body mass index (BMI). The observed increase in ovarian cancer with increasing BMI did not differ appreciably by age, year of birth, ethnicity, education, age at menarche, parity status, family history of ovarian or breast cancer, cigarette smoking, or alcohol consumption, but did vary with menopausal hormone use, with BMI related to risk in never users only.
Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118,964 women with breast cancer from 117 epidemiological studies (2012)
 Based on a meta-analysis that included 118,964 women with breast cancer from 117 epidemiological studies, breast cancer risk increased significantly with earlier age at menarche and later age at menopause, and was higher in premenopausal than post-menopausal women. Risks were also examined by sociodemographic, personal, and tumor characteristics.
Cigarette smoking, alcohol intake, and thyroid cancer risk: A pooled analysis of five prospective cohorts in the United States (2012)
 Thyroid cancer risks associated with cigarette smoking and alcohol intake were examined in a pooled study of five prospective cohorts that included 1,003 men and women with thyroid cancer. Cigarette smoking characteristics (current vs. never, intensity, duration, and pack-years), as well as alcohol consumption (>7 drinks per week vs. 0), were associated with reduced thyroid cancer risks.
Common obesity-related genetic variants and papillary thyroid cancer risk (2012)
 Associations between papillary thyroid cancer (PTC) risk and 575 tag single nucleotide polymorphisms (SNPs) in 23 obesity-related gene regions were examined in a pooled case-control study of 341 PTC cases and 444 controls. Nine of 10 SNPs associated with PTC were located in the fat mass and obesity associated gene region and the other was located in the insulin receptor region. None of these associations remained statistically significant after adjustment for multiple comparisons, leading the authors to conclude that obesity-related gene polymorphisms do not play an important role in risk of PTC.
Physical activity, diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies (2012)
 Thyroid cancer risk was not associated with a history of diabetes in a pooled study of five prospective cohorts that included 818 men and women with thyroid cancer. Risk increased with increasing physical activity in overweight or obese individuals, but was not related to physical activity in those with normal weight.
Common genetic variants in the 8q24 region and risk of papillary thyroid cancer (2012)
 A case-control study of 344 papillary thyroid cancer cases and 452 age- and sex-matched controls evaluated 157 tag single nucleotide polymorphisms (SNPs) in the 8q24 gene-poor region. No associations were found for three SNPs that have been consistently linked with thyroid cancer. Thirteen other SNPs were associated with thyroid cancer risk but none of the associations remained statistically significant after adjustment for possible false discovery.
Common genetic variants in sex hormone pathway genes and papillary thyroid cancer risk (2012)
 In a pooled case-control study of 344 papillary thyroid cancer cases and 452 controls, we found no evidence that thyroid cancer risk was associated with 1134 tag single nucleotide polymorphisms (SNPs) in 58 candidate genes involved in hormone metabolism pathways.
Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies (2011)
 Risk of thyroid cancer increased with increasing BMI in both men and women in a pooled analysis of 388 female and 768 male thyroid cancer cases from five cohort studies. BMI-related risks were not modified by other thyroid cancer risk factors, including education, race, marital status, cigarette smoking, and alcohol consumption.
A role for XRCC2 gene polymorphisms in breast cancer risk and survival (2011)
 In a study involving discovery (Sheffield Breast Cancer Study), replication (Utah Breast Cancer Study), and survival analysis (USRT and 5 other cohorts), 12 XRCC2 tagging SNPs were evaluated. The most significant associations observed were increased breast cancer risk with the XRCC2 (rs3218408) SNP and poor breast cancer survival with the XRCC2 coding R188H SNP (rs3218536).
Common genetic variants related to genomic integrity and risk of papillary thyroid cancer (2011)
 In a pooled case-control study of 344 PTC cases and 452 matched controls, we examined the role of 5,077 tag single nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function, cell cycle control and signaling pathways. Nine SNPs had P-values <0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P <0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3, and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC.
Hormone-related risk factors and postmenopausal breast cancer among nulliparous vs parous women: an aggregated study (2011)
 Nulliparity is an established breast cancer risk factor, especially when compared with parity at young ages. The authors aggregated data from four prospective studies including 32,641 nulliparous (1,612 breast cancers) and 204,270 parous women (8,180 breast cancers) to examine the hypothesis that nulliparity may increase susceptibility to established postmenopausal breast cancer risk factors. One of the studies included in the aggregated report was the USRT cohort study. The results suggested that breast cancer risk from common hormonal factors does not differ by parity.
Body mass index and mortality among 1.46 million white adults (2010)
 Using pooled data from 21 cohort studies in the National Cancer Institute Cohort Consortium, including the U. S. Radiologic Technologist Study, researchers found that overweight, obesity, and possibly underweight were associated with elevated mortality from all causes in white adults. All-cause mortality was lowest in individuals with BMI in the range of 20.0-24.9.
Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts (2010)
 In an aggregated analysis of 943,759 individuals from seven cohort studies, 2,454 pancreatic cancers were diagnosed during an average follow-up of 6.9 years. Statistically significant increased risks were observed in overweight (BMI= 25 to <30) and obese (BMI= 30 to <35) men and women compared to those with normal BMI levels, and risks increased significantly for women and nearly significantly for men with increasing BMI. Age, gender, cigarette smoking, physical activity, and history of diabetes did not alter the relationship between BMI and pancreatic cancer risk.
Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the Breast Cancer Association Consortium: a combined case-control study (2010)
 In a study of 26,349 invasive breast cancer cases and 32,308 comparison subjects from 21 case-control studies included in the Breast Cancer Association Consortium, researchers evaluated 12 recently identified breast cancer genetic susceptibility variants (10Q26-RS2981582 [FGFR2], 8q24-rs13281615, 11p15-rs3817198 [LSP1], 5q11-rs889312 [MAP3K1], 16q12-rs3803662 [TOX3], 2q35-rs13387042, 5p12-rs10941679 [MRPS30], 17q23-rs6504950 [COX11], 3p24-rs4973768 [SLC4A7], CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314) in combination with other cancer risk factors, including age at menarche, parity, number of live births, age at first birth, and body mass index. The breast cancer risks associated with these genetic polymorphisms did not differ significantly according to BMI or reproductive history.
Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2 (2009)
 More than 800 promising associations from genome-wide association studies (GWAS) of breast cancer were tested in two stages among 37,012 cases and 40,069 controls from 33 studies. Strong evidence for additional susceptibility loci on chromosomes 3p (rs4973768: per-allele OR=1.11, 95% CI=1.08-1.13) and 17q (rs6504950: per-allele OR=0.95, 95% CI=0.92-0.97) were observed. Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.
Association of ESR1 gene tagging SNPs with breast cancer risk (2009)
 A comprehensive SNP-tagging study of the ESR1 gene in more that 55,000 breast cancer cases and controls from the Breast Cancer Association Consortium revealed no large associations of common ESR1 gene variants with breast cancer risk. A marginally significant increase primarily in estrogen-receptor positive breast cancer risk was observed for SNP rs3020314 tagging a region of ESR1 intron 4.
Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium (2009)
 Based on a combined analysis of more than 30,000 breast cancer cases and 30,000 controls from 30 studies in the Breast Cancer Association Consortium, persuasive evidence against an overall association between invasive breast cancer risk and five polymorphisms that were associated inconclusively in previous studies was observed. The polymorphisms studied were ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315.
A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1) (2009)
 The Cancer Genetic Markers of Susceptibility (CGEMS) consortium, in which the U.S. Radiologic Technologists Study participates, undertook a three-stage genome-wide association study of breast cancer in 9,770 cases and 10,799 controls. Strong associations were confirmed for six previously reported genomic regions on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26, and 16q12.1 and new risk alleles were identified at 1p11.2 and 14q24.1.
Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls (2008)
 An evaluation of data for 23,257 women with ovarian cancer and 87,303 women without ovarian cancer from 45 studies in 21 countries revealed that oral contraceptive use provides long-term protection against ovarian cancer. The authors estimate that oral contraceptives have already prevented about 200,000 ovarian cancers and 100,000 ovarian cancer deaths, and that at least 30,000 ovarian cancers per year will be prevented during the next few decades.
Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics (2008)
 The clinical presentation of breast cancer was evaluated among 23,039 invasive breast cancer cases and 26,272 controls from 20 studies, and survival after diagnosis was evaluated among 13,527 cases from 13 studies, according to common variants in five susceptibility loci (FCFR2, TNRC9, MAP3K1, 8q24, and LSP1) recently identified by the Breast Cancer Association Consortium. Variants in the FCFR2 (fibroblast growth receptor 2) gene and the 8q24 region were more strongly related to estrogen-receptor positive vs. ER-negative and to low-grade vs. high-grade tumors. Survival was not associated with these loci after adjustment for known indicators of prognosis. These findings indicate that pathological subtype of breast cancer is influenced by common genetic variants and supports the theory that ER-positive and ER-negative tumors differ biologically.
A common coding variant in CASP8 is associated with breast cancer risk (2007)
 The Breast Cancer Association Consortium (BCAC), which includes the U.S. Radiologic Technologist Study, was established to conduct combined case-control studies to confirm genetic associations with breast cancer. Nine single-nucleotide polymorphisms that were previously associated with breast cancer were studied. BCAC found evidence of an association with a common coding variant in the CASP8 gene.
Genome-wide association study identifies multiple novel breast cancer susceptibility loci (2007)
 The Breast Cancer Association Consortium (BCAC), which includes the U.S. Radiologic Technologist Study, was established to conduct combined case-control studies to confirm genetic associations with breast cancer. To identify additional breast cancer susceptibility alleles, BCAC conducted a two-stage genome-wide association study, followed by a third stage in which 30 single-nucleotide polymorphisms were tested for confirmation in cases and controls from 22 studies.
Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Consortium (2006)
 Large sample sizes are needed to detect and confirm, at appropriate levels of statistical significance, genetic variants that are associated with modest increases in cancer risk. We participate in the Breast Cancer Association Consortium, which includes more than 20 international collaborative groups, with a combined sample size in excess of 30,000 breast cancer cases and 30,000 controls. The current study evaluated 16 single-nucleotide polymorphisms that were previously evaluated by at least 3 of the participating centers. Five of the SNPs were found to be associated with breast cancer risk, while 11 were not.