Case-control studies of cancers of the bladder, kidney, prostate, pancreas, esophagus, stomach, lung, brain, and head and neck, as well as non-Hodgkins lymphoma and multiple myeloma, are in progress. Cigarette smoking is an important risk factor for several cancers examined by OEEB investigators. The observation of an increase in smoking-related bladder cancer in New England was confirmed in the NIH-AARP cohort, with a four-fold risk in current cigarette smokers compared to non-smokers. We also observed for the first time that the populationattributable risk for ever smoking and bladder cancer in women had reached the same level asthat in men (0.52 and 0.50, respectively). In a pooled analysis, current and former cigarettesmokers had an elevated risk of pancreatic cancer compared to never smokers, and significanttrends were found with increasing numbers of cigarettes and smoking duration. Importantly,risk of pancreatic cancer reached the level of never smokers about 20 years after quitting. Renalcell cancer (RCC) risk increased with increasing duration and pack-years of cigarette smoking inthe U.S. Renal Cell Cancer Study. A null association between cigarette smoking and multiplemyeloma was reported in a pooled analysis, confirming that smoking is not a risk factor for thiscancer. Significant inverse associations were found between alcohol consumption and RCC in the NIH-AARPand PLCO cohorts. Alcohol consumption was also inversely associated withmultiple myeloma in a pooled analysis and in a case-spouse study.High BMI was linked to increased risks of several cancers including RCC, colorectalcancer in men, pancreatic cancer in adults with a substantial gain in adiposity after age 50,esophageal cancer, and multiple myeloma. Regarding physical activity, low levelsof transportation-related activity and low leisure-time activity were linked with higher risks ofRCC in whites, but not blacks, in the U.S. Similarly, in a large prospective study of Chinesewomen, high occupational activity and high leisure exercise in post-menopausal women wereassociated with reduced breast cancer risks. To better understand the genetic basis of obesity and other anthropometric traits, large-scale meta-analyses of GWAS for the extremes of BMI and height (upper and lower 5th percentiles) and clinical classes of obesity and BMI were undertaken, yielding four new loci for height,seven new loci for clinical classes of obesity, and 57 new loci for BMI. Further GWASmeta-analyses for waist and hip-related measurements in over 220,000 individuals identified 33new loci associated with waist-hip ratio and 19 new loci for waist and hip circumferencemeasures. Sex-specific meta-analyses of GWAS for anthropometric traits identified six newloci for waist-hip ratio and one for waist circumference in women, but not men.216 No new lociwere identified in a smaller meta-analysis of GWAS for BMI in young adults, but fourestablished loci were found to have significantly stronger effects in adolescence and youngadulthood. OEEB investigators have led molecular studies of circulating adipokines toelucidate the potential mechanisms linking obesity to various malignancies. A prospective studyof multiple myeloma in PLCO found consistent evidence of an increased risk among those withlow circulating levels of adiponectin; preliminary findings from a follow-up study in the NCICohort Consortium have confirmed this observation. Low adiponectin levels were alsoassociated with an increased risk of RCC in one prospective study.Consumption of processed meat was associated with an increased risk of bladder cancer.Consumption of barbecued meat and measured PAHs (benzo(a)pyrene) were associated with anincreased risk of RCC, with higher risks among African Americans and current smokers. Astudy of folate intake found a reduced risk of colorectal cancer associated with high compared tolow natural folate intake among PLCO participants with the highest global DNA methylationlevels. Pre-diagnostic hypomethylation was associated with higher gastric cancer risk, with astronger association among those with high isoflavone and folic acid intake in the ShanghaiWomens Health Study.RCC was associated with a history of hypertension and chronic kidney disease, withhigher risks among blacks than whites. A GWAS of RCC discovered the first susceptibility locifor sporadic disease and contributed to the discovery of two additional loci. AnotherGWAS of RCC among African Americans identified a variant important for the clear cellsubtype. Analyses evaluating gene-environment interactions with obesity, hypertension andother RCC risk factors are underway.Two pooled analyses of pancreatic cancer reported significant 1.8 and 1.9-fold risks associatedwith diabetes, with elevated risk apparent as much as 20 years prior to cancer diagnosis.Hay fever and animal allergies were linked to reduced risks of pancreatic cancer. Increasedesophageal cancer risk was associated with a history of gastro-esophageal reflux,211 and gastriccancer was linked to low levels of plasma pepsinogen 1 and high levels of plasma pepsinogen 2,indicating independent effects of these circulating pepsinogens.Higher risks of kidney cancer were associated with having had a hysterectomy in the NIH-AARPand PLCO cohorts and in a subsequent meta-analysis of seven cohort and six case-controlstudies. RCC risk was reduced among women 30 years of age at first birth; the associationwas significant among white, but not black, women. A reduced risk of bladder cancer wasassociated with parity, late menarche, and estrogen and progestin use in the NIH-AARPcohort.Use of nonsteroidal anti-inflammatory drugs was associated with a reduced risk of bladdercancer in a case-control study and in a pooled analysis of three cohort studies. It has alsobeen linked to a lower esophageal cancer risk, as well as a 30% lower risk of colorectalcancer, which was modified by two SNPs at chromosomes 12 and 15. Acetaminophen use wasassociated with an increased risk of RCC.
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| Bock, Cathryn H; Ruterbusch, Julie J; Holowatyj, Andreana N et al. (2018) Renal cell carcinoma risk associated with lower intake of micronutrients. Cancer Med 7:4087-4097 |
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| Colt, Joanne S; Hofmann, Jonathan N; Schwartz, Kendra et al. (2017) Antihypertensive medication use and risk of renal cell carcinoma. Cancer Causes Control 28:289-297 |
| Suarez-Sarmiento, Alfredo; Yao, Xiaopan; Hofmann, Jonathan N et al. (2017) Ethnic disparities in renal cell carcinoma: An analysis of Hispanic patients in a single-payer healthcare system. Int J Urol 24:765-770 |
| Zhang, Yuan; Hofmann, Jonathan N; Purdue, Mark P et al. (2017) Logistic Bayesian LASSO for genetic association analysis of data from complex sampling designs. J Hum Genet 62:819-829 |
| Purdue, Mark P; Stewart, Patricia A; Friesen, Melissa C et al. (2017) Occupational exposure to chlorinated solvents and kidney cancer: a case-control study. Occup Environ Med 74:268-274 |
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