Search

In 2018, the authors reported estimates of the number and proportion of cancers attributable to potentially modifiable risk factors in 2014 in the United States. These data are useful for advocating for and informing cancer prevention and control. Herein, based on up‐to‐date relative risk and cancer occurrence data, the authors estimated the proportion and number of invasive cancer cases (excluding nonmelanoma skin cancers) and deaths, overall and for 30 cancer types among adults who were aged 30 years and older in 2019 in the United States, that were attributable to potentially modifiable risk factors. These included cigarette smoking; second‐hand smoke; excess body weight; alcohol consumption; consumption of red and processed meat; low consumption of fruits and vegetables, dietary fiber, and dietary calcium; physical inactivity; ultraviolet radiation; and seven carcinogenic infections. Numbers of cancer cases and deaths were obtained from data sources with complete national coverage, risk factor prevalence estimates from nationally representative surveys, and associated relative risks of cancer from published large‐scale pooled or meta‐analyses. In 2019, an estimated 40.0% (713,340 of 1,781,649) of all incident cancers (excluding nonmelanoma skin cancers) and 44.0% (262,120 of 595,737) of all cancer deaths in adults aged 30 years and older in the United States were attributable to the evaluated risk factors. Cigarette smoking was the leading risk factor contributing to cancer cases and deaths overall (19.3% and 28.5%, respectively), followed by excess body weight (7.6% and 7.3%, respectively), and alcohol consumption (5.4% and 4.1%, respectively). For 19 of 30 evaluated cancer types, more than one half of the cancer cases and deaths were attributable to the potentially modifiable risk factors considered in this study. Lung cancer had the highest number of cancer cases (201,660) and deaths (122,740) attributable to evaluated risk factors, followed by female breast cancer (83,840 cases), skin melanoma (82,710), and colorectal cancer (78,440) for attributable cases and by colorectal (25,800 deaths), liver (14,720), and esophageal (13,600) cancer for attributable deaths. Large numbers of cancer cases and deaths in the United States are attributable to potentially modifiable risk factors, underscoring the potential to substantially reduce the cancer burden through broad and equitable implementation of preventive initiatives. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, few studies to date have examined associations between moderate to vigorous physical activity (MVPA) and sitting time with quality of life in cancer survivors compared with a cancer‐free group. The current study examined differences in global mental health (GMH) and global physical health (GPH) across levels of MVPA and sitting among cancer survivors and cancer‐free participants. Methods: Cancer Prevention Study II participants (59.9% of whom were female with an age of 77.8 ± 5.8 years) were grouped as: 1) survivors who were 1 to 5 years after diagnosis (3718 participants); 2) survivors who were 6 to 10 years after diagnosis (4248 participants); and 3) cancer‐free participants (ie, no history of cancer; 69,860 participants). In 2009, participants completed MVPA, sitting, and Patient‐Reported Outcomes Measurement Information System GMH/GPH surveys. Mean differences in GMH and GPH T scores across MVPA (none, 0 to <7.5, 7.5 to <15, 15 to <22.5, and ≥22.5 metabolic equivalent [MET]‐hours/week) and sitting (0 to <3, 3 to <6, and ≥6 hours/day) were assessed using multivariate generalized linear models. Results: The mean GMH and GPH scores were statistically significantly higher in cancer‐free participants compared with cancer survivor groups, although the differences were not clinically meaningful (mean difference of 0.52 for GMH and 0.88 for GPH). More MVPA was associated with higher GMH and GPH scores for all 3 groups (P for trend <.001), and differences between the least and most active participants were found to be clinically meaningful (mean differences of ≥4.34 for GMH and ≥6.39 for GPH). Similarly, a lower duration of sitting was associated with higher GMH and GPH scores for all groups (P for trend <.001), with clinically meaningful differences observed between the least and most sedentary participants (mean differences of ≥2.74 for GMH and ≥3.75 for GPH). Conclusions: The findings of the current study provide evidence of the importance of increased MVPA and decreased sitting for improved health in older adults with or without a prior cancer diagnosis. More physical activity appears to be associated with higher global mental and physical health for short‐term and long‐term cancer survivors, and differences between the least and most active individuals are found to be clinically meaningful. Similarly, a lower duration of sitting is associated with higher global mental and physical health for short‐term and long‐term cancer survivors, with clinically meaningful differences noted between those who are the least and most sedentary. [ABSTRACT FROM AUTHOR]

Cadmium and lead are persistent environmental toxins that are known or probable carcinogens, based on evidence for causality for nonhematologic cancers. Associations of these metals with risk of non‐Hodgkin lymphoma (NHL) and multiple myeloma (MM) are unknown but biologically plausible. To examine the associations of circulating levels of lead and cadmium exposure with risk of B‐cell NHL (B‐NHL) and multiple myeloma, we conducted a nested case‐control study among 299 incident B‐cell NHLs and 76 MM cases within the Cancer Prevention Study‐II Nutrition Cohort (CPS‐II NC). Each case was incidence‐density matched to two eligible controls on age, race, sex and blood draw date. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for lymphoid malignancies overall and stratified by subtype. We observed a significant positive association between high erythrocyte lead concentration and risk of lymphoid malignancies overall (RR = 1.16, 95% CI: 1.02‐1.33 per 17.6 μg/L (1 standard deviation [SD])) and follicular lymphoma in particular (RR = 1.80, 95% CI: 1.15‐2.80 per SD). In contrast, there was no association between erythrocyte cadmium and risk of B‐NHL (RR = 0.89, 95% CI: 0.75‐1.06 per 0.37 μg/L [1 SD]), or any B‐NHL subtypes; but a strong inverse association with MM risk (RR = 0.59, 95% CI: 0.38‐0.89, per SD). Results from our study suggest a positive association between erythrocyte lead level and risk of lymphoid malignancies and a possible inverse association between cadmium and myeloma. Additional research is needed to confirm and further explore these findings. What's new? Human exposure to cadmium and lead, which are dispersed widely in the environment, occurs primarily through food consumption and tobacco smoking. These highly toxic heavy metals are known to harm the hematopoietic system, potentially raising hematologic cancer risk. In this investigation of data from the U.S. Cancer Prevention Study II Nutrition Cohort, erythrocyte lead concentration was positively associated with lymphoid malignancy risk, most notably follicular lymphoma. Erythrocyte cadmium levels were not associated with lymphoid malignancies overall but were inversely associated with multiple myeloma among older persons. This observation warrants further exploration of the relationship between cadmium and hematologic cancers. [ABSTRACT FROM AUTHOR]

Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health‐based air‐quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution‐derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described. [ABSTRACT FROM AUTHOR]

The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans. [ABSTRACT FROM AUTHOR]

Benzene is considered a carcinogen, mostly based on evidence of causality for myeloid leukemia from high levels of exposure in occupational studies. We used United States Environmental Protection Agency National Ambient Toxics Assessment (NATA) estimates of low‐level ambient benzene to examine potential associations for the general public between benzene exposure and risk of hematologic cancers. Exposure was estimated by linking participants' residential address to the NATA benzene estimates for that census tract. Among 115,996 American Cancer Society Cancer Prevention Study‐II Nutrition cohort participants (52,554 men, 63,442 women), 2,595 were diagnosed with incident hematologic cancer between 1997 and 2013. Extended Cox regression modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Among all participants, ambient benzene was positively associated with myelodysplastic syndromes (HR = 1.16, 95% CI: 1.01–1.33 per μg/m3) and T‐cell lymphoma (HR = 1.29, 95% CI: 1.08–1.53 per μg/m3). Among men, ambient benzene was also positively associated with any hematologic malignancy (HR = 1.07, 95% CI: 1.01–1.15 per μg/m3) and follicular lymphoma (HR = 1.28, 95% CI: 1.09–1.50 per μg/m3). No significant associations were observed for women only, but associations were suggestive for MDS and T‐cell lymphoma. It is possible that the NATA ambient benzene estimates are a better proxy for benzene exposure for men than women in this cohort. The results of this study support an association between ambient benzene and risk of hematologic malignancies, particularly MDS, T‐cell lymphoma and follicular lymphoma. More research in large scale or pooled studies is needed to further explore these associations. What's new? Occupational exposure to benzene is a known cause of primary acute myeloid leukemia. Benzene is also suspected of causing lymphoid malignancies, though little is known about possible associations. Here, risk of hematologic cancers was investigated in the context of ambient benzene exposure in the general population. Based on estimates from the U.S. Environmental Protection Agency National Ambient Toxics Assessment, low‐level ambient benzene exposure is associated with elevated risk of myelodysplastic syndromes and T‐cell and follicular lymphomas, especially among men. Larger studies are needed to better understand ambient benzene exposure as a risk factor for hematologic cancer subtypes. [ABSTRACT FROM AUTHOR]

Summary: There is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study‐II (CPS‐II), and a meta‐analysis of published cohort studies. Among 152 090 CPS‐II participants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170 MDS were identified over 21 years of follow‐up. In CPS‐II, body mass index (BMI) was weakly associated with risk of CML (hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99–1·09 per 1 unit increase in BMI), AML (HR = 1·01, 95% CI: 0·98–1·03) and MDS (HR = 1·03, 95% CI: 0·99–1·07). After controlling for other anthropometric factors, no clear association was observed for height, BMI at age 18 years or weight change. In the meta‐analysis (n = 7117 myeloid leukaemias), BMI 25–29·9 kg/m2 (HRpooled = 1·36, 95% CI: 1·12–1·59) and BMI ≥30 kg/m2 (HRpooled = 1·43, 95% CI: 1·18–1·69) were associated with higher risk of myeloid leukaemia overall, compared to a BMI <25 kg/m2. Likewise, BMI ≥25 kg/m2 was positively associated with both AML and CML risk individually in the meta‐analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk. [ABSTRACT FROM AUTHOR]

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58–0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92–1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47–2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2, 1.93 [1.46–2.56] and current smoking (vs. never, 1.30 [1.07–1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted. What's new? In ovarian cancer, risk factor profiles may be associated with disease subtypes defined by aggressiveness independent of histology, according to this new analysis. In this large consortium‐based prospective study, the authors classified ovarian tumors according to aggressiveness, based on years between diagnosis and death. They hypothesized that pre‐diagnosis exposure to risk factors, such as smoking, BMI, family history, and pregnancy, would influence whether an ovarian cancer developed on a path toward more aggressive or less aggressive disease. Indeed, in clustering analysis, risk factor associations tracked by tumor aggressiveness rather than histotypes. Smoking and BMI, two modifiable risk factors, were associated with highly aggressive disease. [ABSTRACT FROM AUTHOR]

Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case–control studies nested within the Cancer Prevention Study‐II (CPS‐II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition – Italy (EPIC‐Italy) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma‐mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random‐effects models with each study result weighted by the within‐ and between‐study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut‐points, cadmium levels were not associated with breast cancer risk in the CPS‐II cohort (continuous RR = 1.01, 95% CI 0.76–1.34), but were inversely associated with risk in the EPIC‐ Italy (continuous RR = 0.80, 95% CI 0.61–1.03) and NSHDS cohorts (continuous RR = 0.73, 95% CI 0.54–0.97). The inverse association was also evident in the meta‐analysis (continuous RR = 0.84, 95% CI 0.69–1.01) with low between‐study heterogeneity. Large differences in lead level distributions precluded a meta‐analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta‐analysis. What's new? Do cadmium and lead cause breast cancer? These two notorious toxic metals tend to linger in the body, and both are classified as carcinogens. Ubiquitous environmental contaminants, they accumulate in women particularly, due to their lower iron levels. Yet no definitive link has been demonstrated between cadmium or lead and breast cancer. Here, the authors analyzed three case–control studies. Across the three studies, a wide range of exposure levels was represented, and each study included a large number of participants. The meta‐analysis revealed no association between high levels of cadmium or lead and breast cancer risk. [ABSTRACT FROM AUTHOR]

The prevalence of excess body weight and the associated cancer burden have been rising over the past several decades globally. Between 1975 and 2016, the prevalence of excess body weight in adults-defined as a body mass index (BMI) ≥ 25 kg/m2 -increased from nearly 21% in men and 24% in women to approximately 40% in both sexes. Notably, the prevalence of obesity (BMI ≥ 30 kg/m2 ) quadrupled in men, from 3% to 12%, and more than doubled in women, from 7% to 16%. This change, combined with population growth, resulted in a more than 6-fold increase in the number of obese adults, from 100 to 671 million. The largest absolute increase in obesity occurred among men and boys in high-income Western countries and among women and girls in Central Asia, the Middle East, and North Africa. The simultaneous rise in excess body weight in almost all countries is thought to be driven largely by changes in the global food system, which promotes energy-dense, nutrient-poor foods, alongside reduced opportunities for physical activity. In 2012, excess body weight accounted for approximately 3.9% of all cancers (544,300 cases) with proportion varying from less than 1% in low-income countries to 7% or 8% in some high-income Western countries and in Middle Eastern and Northern African countries. The attributable burden by sex was higher for women (368,500 cases) than for men (175,800 cases). Given the pandemic proportion of excess body weight in high-income countries and the increasing prevalence in low- and middle-income countries, the global cancer burden attributable to this condition is likely to increase in the future. There is emerging consensus on opportunities for obesity control through the multisectoral coordinated implementation of core policy actions to promote an environment conducive to a healthy diet and active living. The rapid increase in both the prevalence of excess body weight and the associated cancer burden highlights the need for a rejuvenated focus on identifying, implementing, and evaluating interventions to prevent and control excess body weight. [ABSTRACT FROM AUTHOR]

In the United States, it is estimated that more than 1.7 million people will be diagnosed with cancer, and more than 600,000 will die of the disease in 2018. The financial costs associated with cancer risk factors and cancer care are enormous. To substantially reduce both the number of individuals diagnosed with and dying from cancer and the costs associated with cancer each year in the United States, government and industry and the public health, medical, and scientific communities must work together to develop, invest in, and implement comprehensive cancer control goals and strategies at the national level and expand ongoing initiatives at the state and local levels. This report is the second in a series of articles in this journal that, together, describe trends in cancer rates and the scientific evidence on cancer prevention, early detection, treatment, and survivorship to inform the identification of priorities for a comprehensive cancer control plan. Herein, we focus on existing evidence about established, modifiable risk factors for cancer, including prevalence estimates and the cancer burden due to each risk factor in the United States, and established primary prevention recommendations and interventions to reduce exposure to each risk factor. [ABSTRACT FROM AUTHOR]

We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin‐like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A‐rs2382112 (ORhom = 3.05, 95%CI = 1.72–5.44, Phom = 1.47 × 10−4), MAST2‐rs12124649 (ORhom = 1.73, 95% CI =1.18–2.54, Phom = 5.24 × 10−3), and INSR‐rs10500204 (ORhom = 1.96, 95% CI = 1.44–2.67, Phom=1.68 × 10−5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR‐rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case‐only analyses using the homozygous minor versus homozygous major model (ORhom = 1.78, 95% CI = 1.30–2.44, Phom = 3.23 × 10−4). The SNP INSR‐rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A‐allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further. [ABSTRACT FROM AUTHOR]

Contemporary information on the fraction of cancers that potentially could be prevented is useful for priority setting in cancer prevention and control. Herein, the authors estimate the proportion and number of invasive cancer cases and deaths, overall (excluding nonmelanoma skin cancers) and for 26 cancer types, in adults aged 30 years and older in the United States in 2014, that were attributable to major, potentially modifiable exposures (cigarette smoking; secondhand smoke; excess body weight; alcohol intake; consumption of red and processed meat; low consumption of fruits/vegetables, dietary fiber, and dietary calcium; physical inactivity; ultraviolet radiation; and 6 cancer-associated infections). The numbers of cancer cases were obtained from the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute; the numbers of deaths were obtained from the CDC; risk factor prevalence estimates were obtained from nationally representative surveys; and associated relative risks of cancer were obtained from published, large-scale pooled analyses or meta-analyses. In the United States in 2014, an estimated 42.0% of all incident cancers (659,640 of 1570,975 cancers, excluding nonmelanoma skin cancers) and 45.1% of cancer deaths (265,150 of 587,521 deaths) were attributable to evaluated risk factors. Cigarette smoking accounted for the highest proportion of cancer cases (19.0%; 298,970 cases) and deaths (28.8%; 169,180 deaths), followed by excess body weight (7.8% and 6.5%, respectively) and alcohol intake (5.6% and 4.0%, respectively). Lung cancer had the highest number of cancers (184,970 cases) and deaths (132,960 deaths) attributable to evaluated risk factors, followed by colorectal cancer (76,910 cases and 28,290 deaths). These results, however, may underestimate the overall proportion of cancers attributable to modifiable factors, because the impact of all established risk factors could not be quantified, and many likely modifiable risk factors are not yet firmly established as causal. Nevertheless, these findings underscore the vast potential for reducing cancer morbidity and mortality through broad and equitable implementation of known preventive measures. CA Cancer J Clin 2018;68:31-54. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene-based and pathway-based analyses by applying the summary-based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction ( ppathway < 0.00625). The two most significant genes were NPAS2 ( pgene = 0.0062) and AANAT ( pgene = 0.00078); the latter being significant after Bonferroni correction. For colorectal cancer, we observed a suggestive association with the circadian rhythm pathway in GAME-ON ( ppathway = 0.021); this association was not confirmed in GECCO ( ppathway = 0.76) or the combined data ( ppathway = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms. [ABSTRACT FROM AUTHOR]

Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER-) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene-environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67-0.88, pint = 1.8 × 10−4). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16-1.59, pint = 1.9 × 10−5) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12-1.43, pint =1.8 × 10−4) and between 8q23-rs13267382 and age at first full-term pregnancy (ORint = 0.89, 95% CI: 0.83-0.95, pint = 5.2 × 10−4). While these results do not suggest any strong gene-environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption is associated with a higher risk of colorectal cancer, but to the authors' knowledge its influence on survival after a diagnosis of colorectal cancer is unclear. The authors investigated associations between prediagnosis and postdiagnosis alcohol intake with mortality among survivors of colorectal cancer.Methods: The authors identified 2458 men and women who were diagnosed with invasive, nonmetastatic colorectal cancer between 1992 (enrollment into the Cancer Prevention Study II Nutrition Cohort) and 2011. Alcohol consumption was self-reported at baseline and updated in 1997, 1999, 2003, and 2007. Postdiagnosis alcohol data were available for 1599 participants.Results: Of the 2458 participants diagnosed with colorectal cancer, 1156 died during follow-up through 2012. Prediagnosis and postdiagnosis alcohol consumption were not found to be associated with all-cause mortality, except for an association between prediagnosis consumption of <2 drinks per day and a slightly lower risk of all-cause mortality (relative risk [RR], 0.86; 95% confidence interval [95% CI], 0.74-1.00) compared with never drinking. Alcohol use was generally not associated with colorectal cancer-specific mortality, although there was some suggestion of increased colorectal cancer-specific mortality with postdiagnosis drinking (RR, 1.27 [95% CI, 0.87-1.86] for current drinking of <2 drinks/day and RR, 1.44 [95% CI, 0.80-2.60] for current drinking of ≥2 drinks/day).Conclusions: The results of the current study do not support an association between alcohol consumption and all-cause mortality among individuals with nonmetastatic colorectal cancer. The association between postdiagnosis drinking and colorectal cancer-specific mortality should be examined in larger studies of individuals diagnosed with nonmetastatic colorectal cancer. Cancer 2017;123:2006-2013. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Prospective cohort studies contribute importantly to understanding the role of lifestyle, genetic, and other factors in chronic disease etiology.Methods: The American Cancer Society (ACS) recruited a new prospective cohort study, Cancer Prevention Study 3 (CPS-3), between 2006 and 2013 from 35 states and Puerto Rico. Enrollment took place primarily at ACS community events and at community enrollment "drives." At enrollment sites, participants completed a brief survey that included an informed consent, identifying information necessary for follow-up, and key exposure information. They also provided a waist measure and a nonfasting blood sample. Most participants also completed a more comprehensive baseline survey at home that included extensive medical, lifestyle, and other information. Participants will be followed for incident cancers through linkage with state cancer registries and for cause-specific mortality through linkage with the National Death Index.Results: In total, 303,682 participants were enrolled. Of these, 254,650 completed the baseline survey and are considered "fully" enrolled; they will be sent repeat surveys periodically for at least the next 20 years to update exposure information. The remaining participants (n = 49,032) will not be asked to update exposure information but will be followed for outcomes. Twenty-three percent of participants were men, 17.3% reported a race or ethnicity other than "white," and the median age at enrollment was 47 years.Conclusions: CPS-3 will be a valuable resource for studies of cancer and other outcomes because of its size; its diversity with respect to age, ethnicity, and geography; and the availability of blood samples and detailed questionnaire information collected over time. Cancer 2017;123:2014-2024. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Study results on overall seroprevalence of Helicobacter pylori and colorectal cancer risk have been inconsistent. However, one study found positive associations with antibodies to specific H. pylori proteins. To follow up on those findings, we assessed associations of 15 H. pylori specific proteins with colorectal cancer incidence in the prospective Cancer Prevention Study- II Nutrition Cohort. Materials and Methods Participants in this nested case-control study included 392 cases and 774 controls who were predominantly elderly (median age at blood draw: 71 years) and Caucasian (98%). Seroreactivity against 15 H. pylori proteins was assessed by fluorescent bead-based multiplex serology and associations with colorectal cancer were estimated using conditional logistic regression. Results Helicobacter pylori serostatus was not associated with colorectal cancer incidence (odds ratio ( OR), 1.17, 95% confidence interval (95% CI), 0.91-1.50). Among individual antigens, GroEl serostatus was associated with colorectal cancer risk ( OR, 1.32, 95% CI: 1.03-1.70), whereas CagM was associated with colon cancer risk only ( OR, 1.35, 95% CI: 1.01-1.80). No dose-response relationships were observed for any of the antigens, including GroEl and CagM. Conclusions The results of our study do not support an association between H. pylori infection and colorectal cancer risk in this elderly, mostly Caucasian population. [ABSTRACT FROM AUTHOR]

Objectives Whether endogenous sex hormones play a role in cardiovascular disease ( CVD) risk in men is unclear. Few studies have examined associations of sex hormones with atherosclerosis measured by coronary artery calcium score ( CACS) and carotid intima-media thickness ( cIMT). We evaluated the association of testosterone (T) and other sex hormones with CACS and cIMT. Methods Using the large multi-ethnic cohort of 3164 men without known CVD in the Multi-Ethnic Study of Atherosclerosis ( MESA), cross-sectional associations of tertiles of endogenous sex hormones with CACS and cIMT were analysed. Results In regard to CAC, there was a significant negative trend (P-trend = 0·02) for CACS>0 over tertiles of free T ( FT) with RRs (95% CI) for the lowest to highest tertiles. There was also a marginally significant positive trend (P-trend = 0·06) for CACS>0 over tertiles of sex hormone-binding globulin ( SHBG) with RRs for the lowest to highest tertiles. There were no significant associations with CACS >0 for tertiles of TT (Total T), bioavailable T ( BT), oestradiol (E2) and dehydroepiandrosterone ( DHEA). There was significantly higher log CACS after adjustment for CVD risk factors for lower TT levels, compared to higher levels, using 9·54 and 10·4 nmol/l as cut-off points. In regard to cIMT, there was a significant positive trend ( P = 0·003) in mean cIMT over the tertiles of BT, but not for TT, FT, E2, DHEA and SHBG. There was significantly lower cIMT after adjustment for CVD risk factors for lower TT levels compared to higher levels. Conclusion In a population of male subjects with no known CVD, lower FT is associated with higher RR of CACS>0 and lower TT is associated with higher log CACS. Lower BT and TT are associated with lower cIMT. While these findings support the positive correlation between low T and coronary atherosclerosis, the opposite findings on cIMT warrant further evaluation. [ABSTRACT FROM AUTHOR]

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; ptrend = 2.84 × 10−4; HRheterozygotes = 0.71; 95% CI: 0.55-0.92; HRhomozygotes = 0.48; 95% CI: 0.31-0.76; p2DF = 1.45 × 10−3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C ( CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend = 6.6 × 10−4; HRheterozygotes = 0.96 95% CI: 0.90-1.03; HRhomozygotes = 1.21; 95% CI: 1.09-1.35; p2DF=1.25 × 10−4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. [ABSTRACT FROM AUTHOR]

Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) causes rare, malignant lymphomas. The role of EBV in other non-Hodgkin lymphomas (NHLs) remains unclear, but mildly reduced immune function could lead to reactivation of EBV and subsequent NHL. We examined the association between prospectively-collected plasma EBV antibodies and NHL risk in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort and conducted a meta-analysis of our and published results. The CPS-II study included 225 NHL cases and 2:1 matched controls. No associations were observed between EBV serostatus or antibody levels and risk of NHL overall. However, when including only the three most common types of NHL (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma), high compared to low early antigen (EA-D) diffuse and BZLF1-encoded replication activator antibodies were associated with approximately 60% higher risk of NHL. Odds ratios (ORs) for EBV nuclear antigen-1 and viral capsid antigen (VCA)-p18 were elevated but not statistically significant. In the meta-analysis, both EA (summary OR = 1.52, 95% confidence interval (CI): 1.16-2.00) and VCA (summary OR = 1.20, 95% CI: 1.00-1.44) were positively associated with NHL risk. These results suggest EBV may be associated with a wider spectrum of NHL subtypes, but further study is needed to confirm and fully understand these associations. [ABSTRACT FROM AUTHOR]

Multiple myeloma ( MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1·5 million participants (including 1388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios ( HRs) and 95% confidence intervals ( CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index ( BMI; HR = 1·22, 95% CI: 1·09-1·35 per 5 kg/m2) and for higher cohort-entry BMI ( HR 1·09, 95% CI: 1·03-1·16 per 5 kg/m2) and waist circumference ( HR = 1·06, 95% CI: 1·02-1·10 per 5 cm). Women who were the heaviest, both in early adulthood ( BMI 25+) and at cohort entry ( BMI 30+) were at greater risk compared to those with BMI 18·5 ≤ 25 at both time points ( HR = 1·95, 95% CI: 1·33-2·86). Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood. [ABSTRACT FROM AUTHOR]

It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested case-control studies within large North-American and European cohorts. Per-allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 ( p < 0.01), but not with IGFBP-3 concentrations ( p > 0.10) or with risk of prostate cancer ( p > 0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance [ SSTR5 (somatostatin receptor 5)-rs197056 (uncorrected p for interaction, 0.001); SSTR5-rs197057 (uncorrected p for interaction, 0.002)]. We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with increased bladder cancer incidence in some, but not all, studies. Many studies had limited statistical power and few examined risk by insulin-use, duration of diabetes or cancer stage. We examined the association between T2DM and bladder cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a large prospective study with information on insulin-use and duration of diabetes. Diabetes and insulin-use were ascertained from a questionnaire at study enrollment in 1992 or 1993 and updated in 1997 and every 2 years thereafter. During follow-up through 2007, 1,852 cases of incident bladder cancer were identified among 172,791 participants. Multivariable adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using extended Cox regression modeling. There were no associations of T2DM with the risk of bladder cancer overall (RR = 1.01, 95% CI: 0.87-1.17), noninvasive disease (RR = 0.93, 95% CI: 0.76-1.14) or invasive disease (RR = 1.13, 95% CI: 0.91-1.40). Compared to participants without T2DM, risk of invasive bladder cancer was higher among participants who had had T2DM for >15 years (RR = 1.63, 95% CI: 1.09-2.43) and among those using insulin (RR = 1.64, 95% CI: 1.18-2.27). These results do not support an association of T2DM with overall bladder cancer incidence, but do suggest positive associations of long-term T2DM and insulin-use or other factors correlated with severe diabetes, with invasive bladder cancer incidence. [ABSTRACT FROM AUTHOR]

Results of studies that examined the relationship between physical activity and non-Hodgkin lymphoid neoplasms (NHL) are inconsistent, and only one study to date examined time spent sitting in relation to NHL. We examined recreational physical activity and leisure-time sitting in relation to risk of NHL in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Between 1992 and 2007, 2,002 incident cases were identified among 146,850 participants who were cancer-free at enrollment. Cox proportional hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) while adjusting for potential confounders. Women who sat for at least 6 hr/day were at 28% higher risk of NHL compared to women who sat for fewer than 3 hr/day. In analyses of specific subtypes, sitting time was associated with risk of multiple myeloma only (6+ vs. 3 hr/day sitting: HR = 2.40, 95% CI: 1.45-3.97). Women who engaged in any recreational physical activity had a nonsignificant 20%-30% lower risk of NHL ( p-trend = 0.05) compared to women who reported no recreational physical activity. Neither leisure-time sitting nor recreational physical activity was associated with risk of NHL or major NHL subtype in men. There was no evidence of statistical interaction between physical activity and sitting time, or between body mass index and physical activity or sitting time. Further research is needed to confirm an association between sitting time and multiple myeloma and explore a possible association between physical activity and NHL. [ABSTRACT FROM AUTHOR]

Addictive behaviors, such as cigarette smoking and coffee drinking, have been associated with a reduced risk of Parkinson's disease (PD). Whether alcohol consumption is also associated with PD risk is less certain. We prospectively followed 132,403 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2005. Alcohol intake was assessed at baseline. Incident cases of PD (n = 605; 389 male and 216 female) were confirmed by treating physicians and medical record review. Relative risks (RRs) were estimated using proportional hazards models, adjusting for age, smoking, and other risk factors. Alcohol consumption was not significantly associated with PD risk. After adjustment for age, smoking, and other risk factors, the RR comparing men consuming 30 or more grams of alcohol per day (highest category) to nondrinker men was 1.29 (95% confidence interval [CI]: 0.90, 1.86; P trend: 0.40), and the RR comparing women consuming 15 or more grams of alcohol (highest category) per day to nondrinker women was 0.77 (95% CI: 0.41, 1.45; P trend: 0.87). Consumption of beer, wine, or liquor was also not associated with PD risk. The results of this large, prospective study do not support an association between alcohol intake and risk of PD. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Ovarian cancer has been associated in epidemiologic studies with postmenopausal hormone use. Whether associations differ by hormone regimen, current status or duration of use is unclear. We examined epithelial ovarian cancer incidence in relation to unopposed estrogen (E-only) and estrogen plus progestin (E + P) among 54,436 postmenopausal women of the Cancer Prevention Study II Nutrition Cohort, a US cohort prospectively followed for cancer incidence since 1992. Demographic, medical, reproductive and lifestyle information was collected at enrollment and updated throughout follow-up via self-administered questionnaire. Extended Cox models were used to estimate age- and multivariate-adjusted relative risk (RR) of ovarian cancer according to hormone regimen, current status and duration of use. During 15 years of follow-up, 297 incident cases were identified. Relative to 'never' use of hormones, current E-only use was associated with a twofold higher risk [RR 2.07, 95% confidence interval (CI) 1.50-2.85]; each 5-year increment of use was associated with a 25% higher risk (RR 1.25, 95% CI 1.15-1.36); ≥20 years of use was associated with a near threefold higher risk (RR 2.89; 95% CI 1.71-4.87; trend p = 0.01). Past E-only use was not significantly associated with ovarian cancer, although a modest increase in risk per each 5-year increment of use was suggested (RR 1.14, 95% CI 0.92-1.41). Neither current nor former E + P use was associated with ovarian cancer risk (RR 1.08, 95% CI 0.86-1.35; RR 1.08, 95% CI 0.68-1.71, respectively, per 5-year increment). These findings suggest that progestins may mitigate some of the detrimental effects of estrogen on the ovarian epithelium. [ABSTRACT FROM AUTHOR]

Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed. CA Cancer J Clin 2010. © 2010 American Cancer Society, Inc. [ABSTRACT FROM AUTHOR]

Background: ST elevation in precordial leads has been associated with genetic syndromes of arrhythmias and sudden death. ST height data in different ethnic groups are limited. Methods: ST height was determined in 4612 African-American, Chinese, Hispanic, and non-Hispanic white men and women aged 45–84 years in the Multiethnic Study of Atherosclerosis (MESA). For leads I, II, and V1 to V6, ST height, measured at the J point and 60 ms after the J point, adjusted for covariates were compared between non-Hispanic white and other ethnic groups using analysis of covariance (ANCOVA). Results: Among men, ST height was significantly different across all ethnic groups at both time points for all leads (P < 0.01), except at the J point for limb lead II (P = 0.2). Among women, differences were also significant at the J point and 60 ms past the J point (P < 0.01). ST height was lowest for non-Hispanic whites in all leads and at both time points. At the J point, Chinese had the highest ST height for leads V1 and V2, whereas African Americans had the greatest ST height for leads I and V3 to V6. At 60 ms past the J point, Chinese men had the greatest ST height for lead I and V1 to V6; and Chinese women had greatest ST height for leads V1 to V3. Conclusions: There were significant differences in ST height among ethnic groups in all ECG leads. The physiological mechanisms and clinical significance of these differences and the possible association with arrhythmias require further study. [ABSTRACT FROM AUTHOR]

Several chemicals have been associated with risk of non-Hodgkin's lymphoma (NHL), many of which are substrates for N-acetyltransferase (NAT) and glutathione S-transferase (GST) enzymes. We investigated the association between polymorphisms in genes coding for these enzymes and NHL risk in a population-based study (389 cases and 535 controls).NAT1slow genotype was associated with a slightly increased risk in women [odds ratios (OR) = 1·4; 95% confidence interval (CI) = 0·9–2·3], but not in men.NAT2slow genotype was not associated with risk in either sex. The two slow genotypes ofNAT1andNAT2combined were associated with a minor increase of risk in women (OR = 1·4; 0·8–2·4). There was no association with theGSTM1orGSTT1null genotype in either sex, irrespective of histological subtypes. Individuals withGSTP1 Valhomozygotes had non-significant excessive risk of marginal zone lymphoma (OR = 1·8; 0·6–5·1) and‘other’ B-cell NHLs (OR = 1·6; 0·7–3·6), but lower risk of diffuse large B-cell lymphoma (OR = 0·2; 0·1–0·96). Risk did not elevate with an increasing number of high-riskGSTalleles in either sex. In summary, althoughNAT1,NAT2,GSTM1,GSTT1, orGSTP1polymorphisms do not appear to be associated with NHL risk overall, there might be gender-specific and subtype-specific associations that require confirmation. [ABSTRACT FROM AUTHOR]

Chromatographic, peptide mapping and mass spectrometric analysis were used to examine hemoglobin (Hb) from heavy drinkers and abstainers for alcohol consumption-related modifications. Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different (p < 0.05) amounts of 'fast' hemoglobin. The presence of higher amounts of 'fast' Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications. To further examine Hb for modifications, tryptic peptides of the 'fast' hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry (PDMS). [14Clacetaldehyde (AcH)-Hb was synthesized in vivo for use as standard. Specific peptides were chosen based on co-migration with radiolabeled peptides from tryptic digest of the [14C]acetaldehyde-Hb. The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides; the two pairs of peptides co-migrated on HPLC. A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb. The modified peptides were found in five of six heavy drinker samples. This is the first description of site-specific AcH-Hb adducts occurring in vivo. The routine detection of such adducts has potential for characterizing usual alcohol intake. [ABSTRACT FROM AUTHOR]

Several chemicals have been associated with risk of non-Hodgkin's lymphoma (NHL), many of which are substrates for N-acetyltransferase (NAT) and glutathione S-transferase (GST) enzymes. We investigated the association between polymorphisms in genes coding for these enzymes and NHL risk in a population-based study (389 cases and 535 controls). NAT1 slow genotype was associated with a slightly increased risk in women [odds ratios (OR) = 1.4; 95% confidence interval (CI) = 0.9-2.3], but not in men. NAT2 slow genotype was not associated with risk in either sex. The two slow genotypes of NAT1 and NAT2 combined were associated with a minor increase of risk in women (OR = 1.4; 0.8-2.4). There was no association with the GSTM1 or GSTT1 null genotype in either sex, irrespective of histological subtypes. Individuals with GSTP1 Val homozygotes had non-significant excessive risk of marginal zone lymphoma (OR = 1.8; 0.6-5.1) and 'other' B-cell NHLs (OR = 1.6; 0.7-3.6), but lower risk of diffuse large B-cell lymphoma (OR = 0.2; 0.1-0.96). Risk did not elevate with an increasing number of high-risk GST alleles in either sex. In summary, although NAT1, NAT2, GSTM1, GSTT1, or GSTP1 polymorphisms do not appear to be associated with NHL risk overall, there might be gender-specific and subtype-specific associations that require confirmation.