Publications by authors named "Alpa V Patel"

183 Publications

Proportion of Cancer Cases Attributable to Physical Inactivity by US State, 2013-2016.

Med Sci Sports Exerc 2021 Oct 4. Epub 2021 Oct 4.

Department of Surveillance and Health Equity Science, American Cancer Society, Atlanta, GA Department of Population Science Research Program, American Cancer Society, Atlanta, GA Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.

Introduction/purpose: Little is known concerning the cancer burden attributable to physical inactivity by state. Our objective was to calculate the proportion of incident cancer cases attributable to physical inactivity among adults aged ≥30 years in 2013-2016 in all 50 states and District of Columbia.

Methods: State-level, self-reported physical activity data from the Behavioral Risk Factor Surveillance System were adjusted by sex, age, and race/ethnicity using national level, self-reported physical activity data from the National Health and Nutrition Examination Survey. Age-, sex-, and state-specific cancer incidence data were obtained from the US Cancer Statistics database. Sex-, age-, and state-specific adjusted prevalence estimates for 8 physical activity categories and cancer-specific relative risks for the same categories from a large-scale pooled analysis were used to calculate PAFs by state for stomach, kidney, esophageal (adenocarcinoma), colon, bladder, breast, and endometrial cancer.

Results: When optimal physical activity was defined ≥5 hours/week of moderate-intensity activity, equivalent to ≥15 metabolic equivalent task (MET)-hours/week, 3.0% (95% CI 2.9%-3.0%) of all incident cancer cases (excluding non-melanoma skin cancers) were attributable to physical inactivity, accounting for an average of 46,356 attributable cases per year. The PAF ranged from 2.3% (95% CI 2.2%-2.5%) in Utah to 3.7% (95% CI 3.4%-3.9%) in Kentucky. By cancer site, the PAF ranged from 3.9% (95% CI 3.6%-4.2%) for urinary bladder to 16.9% (95% CI 16.1%-17.7%) for stomach.

Conclusion: Our results indicate that promoting physical activity through broad implementation of interventions could prevent many cancer cases. Over 46,000 cancer cases annually could be potentially avoided if the American population met the recommended 5 hours/week of moderate-intensity (or 15 (MET)-hours/week) physical activity.
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http://dx.doi.org/10.1249/MSS.0000000000002801DOI Listing
October 2021

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.

J Transl Genet Genom 2021 17;5:200-217. Epub 2021 Jun 17.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk.

Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis.

Results: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, = 1.6 × 10) and FL (β = 11.4, SE = 5.82, = 0.02) but not DLBCL ( = 1.0) or MZL ( = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, = 2.4 × 10). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity.

Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.
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http://dx.doi.org/10.20517/jtgg.2021.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494431PMC
June 2021

Prospective COVID-19 related changes in physical activity and sedentary time and associations with symptoms of depression and anxiety.

Ment Health Phys Act 2021 Oct 28;21:100425. Epub 2021 Sep 28.

Dept. of Population Science, American Cancer Society 3380 Chastain Meadows Pkwy NW Kennesaw, GA 30144 USA.

Problem: The COVID-19 pandemic is associated with psychological distress. Decreased moderate-vigorous physical activity (MVPA) and increased sedentary time may be exacerbating pandemic-related symptoms of anxiety and depression, but existing studies exploring these associations are almost entirely cross-sectional.

Methods: Reported data from 2018 and Summer 2020 were used to create change categories based on compliance with MVPA guidelines and relative sedentary time. Participants completed the Patient Health Questionnaire-4 (PHQ-4) in Summer 2020. Associations among changes in MVPA and sedentary time (separately and jointly) with psychological distress (total PHQ-4 score) were examined with ordinal logistic regression and associations with depressive or anxiety symptoms were examined with logistic regression.

Results: Among 2,240 participants (65% women, mean age 57.5 years), 67% increased sedentary time and 21% became inactive between the two time points. After multivariate adjustment, participants who became (OR = 1.71, 95% CI: 1.05-2.78) or remained inactive (OR = 2.07, 1.34-3.22) were more likely to experience depressive symptoms compared to those who remained active. Participants who increased sedentary time were also more likely to experience depressive symptoms compared to those who maintained sedentary time (OR = 1.78, 1.13-2.81). Jointly, those who increased sedentary time while remaining (OR = 3.67, 1.83-7.38) or becoming inactive (OR = 3.02, 1.44-6.34) were much more likely to have depressive symptoms compared to the joint referent (remained active/maintained sedentary time). Associations with anxiety symptoms were not statistically significant.

Conclusions: These findings support the value of promoting MVPA and limiting sedentary time during stressful events associated with psychological distress, like the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.mhpa.2021.100425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483810PMC
October 2021

Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis.

Sci Rep 2021 Oct 5;11(1):19787. Epub 2021 Oct 5.

Department of Breast Surgery, Copenhagen University Hospital, Herlev, Denmark.

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10 and 4.42 × 10). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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http://dx.doi.org/10.1038/s41598-021-99409-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492709PMC
October 2021

Stressors and Other Pandemic-related Predictors of Prospective Changes in Psychological Distress.

Lancet Reg Health Am 2021 Sep 9:100069. Epub 2021 Sep 9.

Department of Population Science, American Cancer Society, Atlanta GA.

Background: Numerous studies have documented mental health challenges during the COVID-19 pandemic. Few studies included pre-pandemic levels of mental health or were comprehensive in assessing factors likely associated with longer-term mental health impacts.

Methods: Analyses used prospective data from a subset of participants in the nationwide Cancer Prevention Study-3 (CPS-3) United States cohort (N=2,359; 1,534 women; 825 men) who completed surveys in 2018 and during the COVID-19 pandemic (July-September 2020). Logistic regressions examined associations of pandemic-related stressors, sociodemographic and other predictors with (i) overall psychological distress (PD) and depression and anxiety separately during the COVID-19 pandemic and (ii) change in PD from 2018 to during the pandemic (low/low; high to low; low to high; high/high).

Findings: During the pandemic, 10% of participants reported moderate-to-severe PD and almost half (42%) reported at least mild PD. Pandemic PD levels were associated with pre-pandemic PD (female OR=5.65; male OR=9.70), financial stressors (female OR=2.48; male OR=3.68), and work/life balance stressors (female OR=3.03; male OR=3.33) experienced since the pandemic began. These stressors also predicted an escalation from low PD in 2018 to high PD during the pandemic. Factors associated with high PD at both time points included younger age, female sex, and financial stressors.

Interpretation: These results highlight the importance of regular mental health assessment and support among those with a history of mental health problems and those experiencing pandemic-related stressors, such as those with caregiving responsibilities or job changes.

Funding: The American Cancer Society funds the creation, maintenance, and updating of the CPS-3.
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http://dx.doi.org/10.1016/j.lana.2021.100069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427739PMC
September 2021

Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.

Breast Cancer Res 2021 08 18;23(1):86. Epub 2021 Aug 18.

Department of Medicine, Huntsman Cancer Institute, Salt Lake City, UT, USA.

Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.

Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15).

Results: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.

Conclusions: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.
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http://dx.doi.org/10.1186/s13058-021-01450-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371820PMC
August 2021

Self-Reported Dietary Supplement Use Is Reproducible and Relatively Valid in the Cancer Prevention Study-3 Diet Assessment Substudy.

J Acad Nutr Diet 2021 Aug 12. Epub 2021 Aug 12.

Background: Dietary supplement use is common, particularly among cancer survivors and those at increased risk for cancer.

Objective: The objectives of this study were to assess 1-year test-retest reproducibility of dietary supplement use reported via food frequency questionnaire (FFQ-1 vs FFQ-2) and relative validity in comparison to repeated 24-hour dietary recalls (FFQ-2 vs DRs).

Design: This ancillary study was conducted within a large prospective cohort, the American Cancer Society's Cancer Prevention Study-3.

Participants/setting: Between 2015 and 2016, 684 participants in the United States (64% women; 62% non-Hispanic White, 23% non-Hispanic Black, and 15% Hispanic) completed two FFQs and up to six unannounced telephone interviewer-administered DRs over 1 year as part of the Cancer Prevention Study-3 Diet Assessment Substudy.

Primary Outcome Measures: FFQs queried current multivitamin-mineral supplement (≥10 components) use, frequency and dose (range) for seven supplements taken individually or as part of a complex (individual/complex) including calcium, vitamins D, C, and E, folic acid, fish oil, and glucosamine. DRs allowed exact reporting of supplement frequency and dose.

Statistical Analyses: Weighted κ statistics were used to evaluate reproducibility between FFQ-1 and FFQ-2 and Spearman correlation coefficients assessed agreement between supplemental nutrient amounts assessed by FFQ-2 and the average of DRs.

Results: Just more than half of the participants reported taking multivitamin-mineral supplements on the baseline FFQ. Kappa statistics for the comparison of categorical responses between FFQ-1 and FFQ-2 were 0.67 for multivitamin-mineral supplements. Kappas for individual/complex supplements ranged from 0.47 for folic acid to 0.74 for vitamin D, with a mean of 0.64. Results were similar between men and women. Spearman correlation coefficients comparing FFQ-2 with the average of DRs (validity) for nutrient intakes from all sources ranged from 0.65 (fish oil for women) to 0.77 (vitamin D for men and calcium for women); results were similar among men and women.

Conclusions: These findings suggest the FFQ used in Cancer Prevention Study-3 has good reproducibility over 1 year and yields estimates comparable to a more detailed assessment for commonly consumed dietary supplements.
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http://dx.doi.org/10.1016/j.jand.2021.07.006DOI Listing
August 2021

Genetic insights into biological mechanisms governing human ovarian ageing.

Nature 2021 08 4;596(7872):393-397. Epub 2021 Aug 4.

Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.

Reproductive longevity is essential for fertility and influences healthy ageing in women, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
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http://dx.doi.org/10.1038/s41586-021-03779-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611832PMC
August 2021

Association between Smoking Cannabis and Quitting Cigarettes in a Large American Cancer Society Cohort.

Cancer Epidemiol Biomarkers Prev 2021 Oct 4;30(10):1956-1964. Epub 2021 Aug 4.

American Cancer Society, Atlanta, Georgia.

Background: Cannabis use is increasing, including among smokers, an at-risk population for cancer. Research is equivocal on whether using cannabis inhibits quitting cigarettes. The current longitudinal study investigated associations between smoking cannabis and subsequently quitting cigarettes.

Methods: Participants were 4,535 adult cigarette smokers from a cohort enrolled in the American Cancer Society's Cancer Prevention Study-3 in 2009-2013. Cigarette quitting was assessed on a follow-up survey in 2015-2017, an average of 3.1 years later. Rates of quitting cigarettes at follow-up were examined by retrospectively assessed baseline cannabis smoking status (), and by frequency of cannabis smoking among recent cannabis smokers (: ≤3 days/month; : 4-19 days/month; : ≥20 days/month). Logistic regression models adjusted for sociodemographic factors, smoking- and health-related behaviors, and time between baseline and follow-up.

Results: Adjusted cigarette quitting rates at follow-up did not differ significantly by baseline cannabis smoking status [never 36.2%, 95% confidence interval (CI), 34.5-37.8; former 34.1%, CI, 31.4-37.0; recent 33.6%, CI, 30.1-37.3], nor by frequency of cannabis smoking (low 31.4%, CI, 25.6-37.3; moderate 36.7%, CI, 30.7-42.3; high 34.4%, CI, 28.3-40.2) among recent baseline cannabis smokers. In cross-sectional analyses conducted at follow-up, the proportion of cigarette smokers intending to quit smoking cigarettes in the next 30 days did not differ by cannabis smoking status ( = 0.83).

Conclusions: Results do not support the hypothesis that cannabis smoking inhibits quitting cigarette smoking among adults.

Impact: Future longitudinal research should include follow-ups of >1 year, and assess effects of intensity/frequency of cannabis use and motivation to quit on smoking cessation.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1810DOI Listing
October 2021

Risk of Late-Onset Breast Cancer in Genetically Predisposed Women.

J Clin Oncol 2021 Jul 22:JCO2100531. Epub 2021 Jul 22.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years.

Methods: A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs.

Results: The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in , , and were found in 3.42% of women diagnosed with estrogen receptor (ER)-negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in , , , and were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in , , and .

Conclusion: This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with and PVs and perhaps with and PVs should be considered for magnetic resonance imaging screening.
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http://dx.doi.org/10.1200/JCO.21.00531DOI Listing
July 2021

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

Am J Hum Genet 2021 07 18;108(7):1190-1203. Epub 2021 Jun 18.

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10).
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http://dx.doi.org/10.1016/j.ajhg.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322933PMC
July 2021

Risk of Breast Cancer Among Carriers of Pathogenic Variants in Breast Cancer Predisposition Genes Varies by Polygenic Risk Score.

J Clin Oncol 2021 Aug 8;39(23):2564-2573. Epub 2021 Jun 8.

Population Health Sciences Department, Weill Cornell Medicine, New York, NY.

Purpose: This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population.

Methods: A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in , , , , , , , , and . PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor-specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC.

Results: The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of , , and carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of and carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk.

Conclusion: PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of and nearly half of carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.
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http://dx.doi.org/10.1200/JCO.20.01992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330969PMC
August 2021

Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (-2df = 1.2 × 10). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (-2df = 1.1 × 10). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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http://dx.doi.org/10.3390/cancers13102370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156547PMC
May 2021

Pilot Randomized Controlled Trial of Feasibility, Acceptability, and Preliminary Efficacy of a Web-Based Physical Activity and Sedentary Time Intervention for Survivors of Physical Inactivity-Related Cancers.

Int J Behav Med 2021 May 6. Epub 2021 May 6.

Department of Population Science, American Cancer Society, Atlanta, GA, USA.

Background: This pilot study explored the feasibility, acceptability, and usability of a web-based intervention for survivors of physical inactivity-related cancers through a two-arm, 12-week randomized controlled trial. Secondarily, this study tested the change in physical activity (PA) and sedentary time with intervention exposure.

Methods: Prior to randomization to the intervention (n = 45) or behavior "as usual" wait-listed control (n = 40) groups, participants completed baseline surveys and an accelerometer protocol. The intervention focused on increasing PA and decreasing sedentary time through social cognitive theory techniques. Follow-up acceptability/usability surveys (intervention group only) and accelerometers were sent after the intervention period. Information on intervention completion, adverse events, and user statistics were collected to determine feasibility. Median login time and mean acceptability/usability scores were calculated.

Results: Participants (mean age = 60 ± 7 years) included female (n = 80, 94%) and male survivors of breast (82%), colon (6%), endometrial (6%), bladder (4%), and kidney (2%) cancer. Seventy-eight (91.7%) participants returned partially or fully complete post-intervention data. There were no reported injuries or safety concerns. Intervention participants logged into the website for a total of 95 min (Q1, Q3 = 11, 204). System usability scores (72 ± 3) indicated above average usability of the website. Changes in time spent active and sedentary were not statistically significantly different between groups (p = 0.45), but within-group changes suggested intervention group participants spent more time active and less time sedentary after the intervention.

Conclusion: Results of this pilot study suggest its feasibility and acceptability for survivors of several inactivity-related cancers. Additional research to determine long-term efficacy is warranted. This low-cost online-only intervention has the potential to have a very broad reach.

Trial Registration: Clinical Trials Number: NCT03983083. Date registered: June 12th, 2019.
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http://dx.doi.org/10.1007/s12529-021-09999-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099708PMC
May 2021

Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts.

Cancer Res 2021 04 5;81(8):2246-2255. Epub 2021 Apr 5.

Division of Cancer Epidemiology and Genetics, National Institutes of Health, Rockville, Maryland.

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. SIGNIFICANCE: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-3093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137527PMC
April 2021

Cancer survivor worries about treatment disruption and detrimental health outcomes due to the COVID-19 pandemic.

J Psychosoc Oncol 2021 24;39(3):347-365. Epub 2021 Feb 24.

Department of Communications, American Cancer Society Cancer Action Network, Washington, DC, USA.

Purpose: We examined cancer survivor worries about treatment, infection, and finances early in the U.S. COVID-19 pandemic.

Design: Closed- and open-ended online survey questions were collected from adult cancer survivors (N = 972).

Methods: Logistic regression identified factors associated with treatment, infection, and financial worry. Thematic qualitative analysis generated information around participants' experiences and worries related to COVID-19 and healthcare.

Findings: Characteristics including marital status, race/ethnicity, cancer type, time since last treatment, education, and age were associated with health and healthcare worry outcomes. Survivors commonly expressed uncertainty about future care, fears about in-person appointments, rationed COVID-19 care, recurrence due to care delays, and distress about untreated symptoms, including mental health issues.

Conclusions: Early in the pandemic, survivors worried about and experienced cancer care delays, COVID infection, and how the pandemic would affect their prognosis.

Implications: Healthcare professionals need to be aware of cancer survivors' concerns and uncertainties to provide appropriate care.
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http://dx.doi.org/10.1080/07347332.2021.1888184DOI Listing
June 2021

The Cancer Prevention Study-3 FFQ Is a Reliable and Valid Measure of Nutrient Intakes among Racial/Ethnic Subgroups, Compared with 24-Hour Recalls and Biomarkers.

J Nutr 2021 03;151(3):636-648

Department of Population Science, American Cancer Society, Atlanta, GA, USA.

Background: Valid assessment of dietary intake in diverse populations is important for studies of chronic disease risk in the United States.

Objectives: We evaluated the reproducibility and validity of a food frequency questionnaire (FFQ) modified for the American Cancer Society's Cancer Prevention Study-3 (CPS-3) prospective cohort, among a racially/ethnically diverse subgroup.

Methods: The Diet Assessment Substudy included 677 CPS-3 participants (64% women; 61% non-Hispanic white, 24% non-Hispanic black, 15% Hispanic), aged 31-70 y, who completed 2 FFQs 1 y apart (FFQ1, FFQ2), 4-6 telephone-administered 24-h dietary recalls (24HRs), and 2 fasting blood samples and 24-h urine collections ∼6 mo apart in the interim. Spearman rank correlation coefficients (ρ) were used to evaluate FFQ reproducibility and validity compared with 24HRs for 67 nutrient exposures. For 18 of these nutrients, we used the method of triads to calculate validity coefficients (VCs, ρ) from pairwise correlations of FFQ2, 24HRs, and biomarkers. Analyses were stratified by sex, race/ethnicity, education, and BMI.

Results: Mean (range) FFQ reproducibility correlations were ρ = 0.65 (0.50-0.91) for men and ρ = 0.63 (0.37-0.89) for women; mean (range) energy-adjusted, deattenuated correlations of FFQ2 with 24HRs were ρ = 0.60 (0.33-0.84) for men and ρ = 0.55 (0.21-0.79) for women. FFQ2 VCs (ρ) among men ranged from 0.42 for β-cryptoxanthin to 0.91 for omega-3 (n-3) fatty acids and, among women, from 0.41 for sodium to 0.79 for total vitamin D. Mean FFQ reproducibility and validity were highest among whites (ρ = 0.68, ρ = 0.58, respectively) and slightly lower among blacks (ρ = 0.57, ρ = 0.49, respectively) and Hispanics (ρ = 0.59, 0.55, respectively). FFQ reproducibility and validity were slightly lower among those with less than a 4-y college degree, and those with a BMI ≥30 kg/m2.

Conclusions: Reproducibility and validity of the CPS-3 FFQ were comparable with similar studies for most nutrients, among all subgroups. These findings support future dietary analyses in the contemporary CPS-3 cohort and other similar cohorts.
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http://dx.doi.org/10.1093/jn/nxaa358DOI Listing
March 2021

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

N Engl J Med 2021 02 20;384(5):440-451. Epub 2021 Jan 20.

From Mayo Clinic, Rochester, MN (C. Hu, S.N.H., R.G., K.Y.L., J.N., J.L., S. Yadav, N.J.B., T.L., J.E.O., C.S., C.M.V., E.C.P., F.J.C.); Harvard University T.H. Chan School of Public Health (H.H., C.G., D.J.H., P.K.), Slone Epidemiology Center at Boston University (K.A.B., J.R.P., L.R.), and Brigham and Women's Hospital (H.E.) - all in Boston; Qiagen, Hilden, Germany (R.S., J.K.); Roswell Park Comprehensive Cancer Center, Buffalo (C.B.A., S. Yao), and Weill Cornell Medicine, New York (R.T.) - both in New York; the University of California, Irvine (H.A.-C., A.Z.), Beckman Research Institute of City of Hope, Duarte (L.B., H.M., S.N., J.N.W.), Keck School of Medicine, University of Southern California, Los Angeles (C. Haiman), and Stanford University School of Medicine, Stanford (E.M.J., A.W.K.) - all in California; the University of Wisconsin-Milwaukee Joseph J. Zilber School of Public Health, Milwaukee (P.A.), and the University of Wisconsin-Madison, Madison (E.S.B., I.M.O., A.T.-D.); the Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, State University of New Jersey, New Brunswick (E.V.B.); the Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta (B.D.C., S.M.G., M.G., J.M.H., E.J.J., A.V.P.); the University of Oxford, Oxford, United Kingdom (D.J.H.); the Fred Hutchinson Cancer Research Center (C.K., P.A.N.) and the Department of Epidemiology, University of Washington (S.L.) - both in Seattle; the Epidemiology Program, University of Hawaii Cancer Center, Honolulu (L.L.M.); the National Institute of Environmental Health Sciences, Durham, NC (K.M.O., D.P.S., J.A.T., C.W.); Vanderbilt University, Nashville (T.P., S.R.); the University of Utah, Salt Lake City (D.E.G.); and the Department of Medicine and the Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (S.M.D., K.L.N.).

Background: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.

Methods: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.

Results: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in and were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in , , and were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in , , and were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in , were not associated with an increased risk of breast cancer.

Conclusions: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).
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http://dx.doi.org/10.1056/NEJMoa2005936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127622PMC
February 2021

Composition of time in movement behaviors and weight change in Latinx, Black and white participants.

PLoS One 2021 8;16(1):e0244566. Epub 2021 Jan 8.

American Cancer Society, Atlanta, Georgia, United States of America.

Background: The relationship between time-use behaviors and prospective weight change is poorly understood.

Methods: A subset of Cancer Prevention Study-3 participants (n = 549, 58% women, 66% non-Latinx white) self-reported weight in 2015 and 2018 and completed an accelerometer protocol for seven days. Sedentary time, sleep, light, moderate, and vigorous intensity physical activity (PA) were treated as a compositional variable and multiple linear regression was used to examine associations between activity composition and weight change stratified by sex and race/ethnicity. Compositional isotemporal substitution analysis was used to quantify change in weight associated with reallocating 30 min./day.

Results: Activity composition was associated with weight change among women (p = 0.007), but not men (p = 0.356), and among Latinx (p = 0.032) and white participants (p = 0.001), but not Black participants (p = 0.903). Replacement of 30 min./day sedentary time with moderate-vigorous PA was associated with 3.49 lbs. loss (-6.76, -0.22) in Latinx participants and replacement with sleep was associated with 1.52 (0.25, 2.79) and 1.31 (0.40, 2.21) lbs. gain in white women and men.

Conclusion: The distribution of time spent in daily behaviors was associated with three-year weight change in women, Latinx, and white participants. This was the first longitudinal compositional study of weight change; thus, more studies are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244566PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793306PMC
May 2021

Breast cancer risk factors by mode of detection among screened women in the Cancer Prevention Study-II.

Breast Cancer Res Treat 2021 Apr 4;186(3):791-805. Epub 2021 Jan 4.

Behavioral and Epidemiology Research Program, American Cancer Society, 250 Williams Street, Atlanta, GA, 30303, USA.

Background: Identifying risk factors for women at high risk of symptom-detected breast cancers that were missed by screening would enable targeting of enhanced screening regimens. To this end, we examined associations of breast cancer risk factors by mode of detection in screened women from the Cancer Prevention Study (CPS)-II Nutrition Cohort.

Methods: Among 77,206 women followed for a median of 14.8 years, 2711 screen-detected and 1281 symptom-detected breast cancer cases were diagnosed. Multivariable-adjusted associations were estimated using joint Cox proportional hazards regression models with person-time calculated contingent on screening.

Results: Factors associated with higher risks of symptom-detected and screen-detected breast cancer included current combined hormone therapy (HT) use (HR 2.07, 95% CI 1.72-2.48 and 1.45, 1.27-1.65, respectively) and history of benign breast disease (1.85, 1.64-2.08 and 1.43, 1.31-1.55, respectively). Current estrogen-only HT use was associated with symptom-detected (1.40, 1.15-1.71) but not screen-detected (0.95, 0.83-1.09) breast cancer. Higher risk of screen-detected but not symptom-detected breast cancer was observed for obese vs. normal body mass index (1.22, 1.01-1.48 and 0.76, 0.56-1.01, respectively), per 3 h/day sitting time (1.10, 1.04-1.16 and 0.97, 0.89-1.06, respectively), and ≥ 2 drinks per day vs. nondrinker (1.40, 1.16-1.69 and 1.27, 0.97-1.66, respectively).

Conclusions: Differences in risk factors for symptom-detected vs. screen-detected breast cancer were observed and most notably, use of combined and estrogen-only HT and a history of benign breast disease were associated with increased risk of symptomatic detected breast cancer.

Impact: If confirmed, these data suggest that such women may benefit from more intensive screening to facilitate early detection.
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http://dx.doi.org/10.1007/s10549-020-06025-2DOI Listing
April 2021

Joint associations of physical activity and body mass index with the risk of established excess body fatness-related cancers among postmenopausal women.

Cancer Causes Control 2021 Feb 13;32(2):127-138. Epub 2020 Nov 13.

American Cancer Society, Behavioral and Epidemiology Research Group, 250 Williams St, Atlanta, GA, USA.

Purpose: Excess body fatness and physical activity independently influence the risk of several types of cancer. However, few studies have examined whether physical activity mitigates the excess risk associated with higher body mass index (BMI).

Methods: We examined the individual and joint associations between BMI (kg/m) and leisure-time moderate-to-vigorous physical activity (MVPA, MET-hours/week) with the risk of three established excess body fatness-related cancers (breast, colon, and endometrial) among 43,795 postmenopausal women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort (1992/1993-2015). Further exclusions for women without an intact uterus resulted in 31,805 women for endometrial cancer analyses. Multivariable Cox proportional hazards regression was used to calculate hazard ratio (HR) and 95% confidence intervals (CIs) with interaction terms to assess multiplicative interaction. The relative excess risk due to interaction (RERI) was calculated to assess additive interaction.

Results: BMI and MVPA were individually associated with breast and endometrial cancer risk, but only BMI was associated with colon cancer risk. In joint analyses, increasing levels of MVPA did not lower the risk of these cancers among obese women. For example, compared to the common referent (BMI 18.5- < 25 kg/m, MVPA > 0- < 7.5 MET-hours/week), BMI ≥ 30 kg/m was associated with a higher risk of breast cancer among women with low MVPA (> 0-< 7.5 MET-hours/week: HR = 1.42, 95% CI: 1.22 - 1.67) and high MVPA (≥ 15 MET-hours/week: HR = 1.53, 95% CI: 1.25 - 1.87; RERI = 0.20, 95% CI: -0.14, 0.54, multiplicative P = 0.64).

Conclusion: Our results do not support the hypothesis that leisure-time physical activity mitigates the excess risk associated with higher BMI for risk of breast, endometrial, or colon cancer among postmenopausal women.
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http://dx.doi.org/10.1007/s10552-020-01365-2DOI Listing
February 2021

Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status: a pooled analysis of 20 prospective cohort studies.

Eur J Epidemiol 2021 Jan 30;36(1):37-55. Epub 2020 Oct 30.

Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.
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http://dx.doi.org/10.1007/s10654-020-00688-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847460PMC
January 2021

Reliability and Validity of Self-reported Muscle-strengthening Exercise in the Cancer Prevention Study-3.

Med Sci Sports Exerc 2021 05;53(5):888-893

Department of Population Science, American Cancer Society, Atlanta, GA.

Purpose: This study examined the 1-yr reliability and construct validity of survey items relating to time spent on muscle-strengthening exercise (MSE) in a subset of a large prospective cohort.

Methods: Participants (n = 293 men, 433 women; age, 32-73 yr) were selected from the Cancer Prevention Study-3. Information was collected using a 1-yr presurvey and postsurvey and four 7-d diaries throughout the year. The presurvey and postsurveys collected time spent on MSE in two ways: one question captured MSE activities performed during a typical 24-h period (24-h survey), and another question captured leisure-time physical activities performed in hours per week and months per year (LTPA survey). Time spent on MSE using the LTPA survey was calculated for individual MSE items and summed for total MSE time. One-year reliability was assessed by comparing the responses between the presurvey and postsurvey using Spearman's correlation coefficients. Construct validity was assessed by computing Spearman's correlation coefficients between responses from the postsurvey items and the diary. Additional analyses were conducted to examine whether reliability or validity varied by sociodemographic factors.

Results: Reliability estimates for all MSE items were moderate (≥0.40) or strong (≥0.60) overall and across demographic strata. Reliability estimates were strongest for total MSE on the LTPA survey (Spearman ρ = 0.75; 95% confidence interval (CI), 0.71-0.78) compared with the 24-h survey (0.59; 95% CI, 0.54-0.64). In contrast, the validity estimates were similarly strong for the total MSE on the LTPA survey (Spearman ρ = 0.71; 95% CI, 0.67-0.75) and the 24-h survey (Spearman ρ = 0.68; 95% CI, 0.64-0.72).

Conclusions: The CPS-3 surveys have acceptable 1-yr reliability and validity for self-reported time spent on MSE. Reliability and validity estimates are acceptable across all sociodemographic subgroups.
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http://dx.doi.org/10.1249/MSS.0000000000002547DOI Listing
May 2021

Self-reported physical activity, sitting time, and mental and physical health among older cancer survivors compared with adults without a history of cancer.

Cancer 2020 01 20;127(1):115-123. Epub 2020 Oct 20.

Department of Population Science, American Cancer Society, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1002/cncr.33257DOI Listing
January 2020

Research Participants' Perspectives on Using an Electronic Portal for Engagement and Data Collection: Focus Group Results From a Large Epidemiologic Cohort.

J Med Internet Res 2020 10 1;22(10):e18556. Epub 2020 Oct 1.

American Cancer Society, Atlanta, GA, United States.

Background: Epidemiologic cohort studies have begun to leverage electronic research participant portals to facilitate data collection, integrate wearable technologies, lower costs, and engage participants. However, little is known about the acceptability of portal use by research participants.

Objective: The aim of this study is to conduct focus groups among a sample of Cancer Prevention Study-3 (CPS-3) participants to better understand their preferences and concerns about research portals.

Methods: CPS-3 participants were stratified based on sex, race and ethnicity, age, and cancer status, and randomly invited to participate. Focus groups used an exploratory case design with semistructured guides to prompt discussion. Using a constant comparison technique, transcripts were assigned codes to identify themes.

Results: Participants (31/59, 52% women; 52/59, 88% White/non-Latinx) were favorably disposed toward using a research participant portal to take surveys, communicate with the study staff, and upload data. Most participants indicated that a portal would be beneficial and convenient but expressed concerns over data safety. Participants stressed the importance of an easy-to-use and trustworthy portal that is compatible with mobile devices.

Conclusions: In addition to being beneficial to researchers, portals may also benefit participants as long as the portals are secure and simple. Participants believe that portals can provide convenient ways to report data and remain connected to the study.
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http://dx.doi.org/10.2196/18556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563628PMC
October 2020

A Large Cohort Study of Body Mass Index and Pancreatic Cancer by Smoking Status.

Cancer Epidemiol Biomarkers Prev 2020 12 22;29(12):2680-2685. Epub 2020 Sep 22.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.

Background: Some evidence suggests the association between body mass index (BMI) and pancreatic cancer risk is weaker among current smokers than among never smokers.

Methods: We examined the association between BMI and pancreatic cancer mortality among adults who reported smoking status at enrollment into Cancer Prevention Study-II in 1982, including 420,543 never smokers, 282,244 former cigarette smokers, and 219,885 current cigarette smokers. After excluding the first 3 years of follow-up to reduce reverse causation, we calculated multivariable-adjusted hazard ratios (HR).

Results: During the full follow-up period from 1985 to 2014, 7,904 participants died of pancreatic cancer. The HR per 5 BMI units was lower among current smokers [HR = 1.14; 95% confidence interval (CI), 1.07-1.20] than never smokers (HR = 1.22; 95% CI, 1.17-1.27), although this difference was not statistically significant ( = 0.06). BMI was significantly less strongly associated with pancreatic cancer mortality among current smokers reporting ≥20 cigarettes/day (HR = 1.10; 95% CI, 1.03-1.18) than among never smokers. During follow-up within 10 years of enrollment, when current smokers at enrollment were the most likely to have still been smoking, BMI was not associated with pancreatic cancer mortality among current smokers (HR = 1.02; 95% CI, 0.90-1.16, = 0.03 for difference between current and never smokers). BMI HRs were similar among former and never smokers.

Conclusions: These results support a weaker association between BMI and pancreatic cancer among current smokers than among never smokers.

Impact: In populations with low smoking prevalence, the pancreatic cancer burden due to BMI is likely to be higher than that predicted by risk estimates from studies including substantial numbers of smokers.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0591DOI Listing
December 2020

Relationship Between Muscle-Strengthening Activity and Cause-Specific Mortality in a Large US Cohort.

Prev Chronic Dis 2020 08 6;17:E78. Epub 2020 Aug 6.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.

Introduction: Muscle-strengthening activity (MSA) has beneficial effects on hypertension, glucose homeostasis, and other health conditions; however, its association with mortality is not as well understood.

Methods: We analyzed data from the Cancer Prevention Study-II Nutrition Cohort (data collection 1982-2014), a prospective US cohort that consisted of 72,462 men and women who were free of major chronic diseases; 18,034 of the cohort died during 13 years of follow-up (2001-2014). We used Cox proportional hazards modeling, controlling for various potential confounding factors, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for MSA (none, >0 to <1 h/wk, 1 to <2 h/wk, and ≥2 h/wk) in relation to mortality risk, independent of and in combination with aerobic physical activity.

Results: The association between MSA and mortality appeared to be nonlinear (quadratic trend P value, <.001). After multivariable adjustment and comparison with no MSA, engaging in less than 2 hours per week of MSA was associated with lowered all-cause mortality (>0 to <1 h/wk: HR = 0.88, 95% CI, 0.82-0.94; 1 to <2 h/wk: HR = 0.90, 95% CI, 0.84-0.97), but engaging in 2 or more hours per week was not associated with reduced risk (HR = 1.01; 95% CI, 0.92-1.09). Associations were similar but not significant for cancer mortality. Engaging in >0 to <1 hr/wk of MSA was associated with a 19% lower risk (HR = 0.81; 95% CI, 0.71-0.92) of cardiovascular disease mortality, but more time spent in MSA was not associated with reduced risk (quadratic trend P value =.005). Associations did not vary by amount of moderate-to-vigorous aerobic physical activity.

Conclusion: Engaging in ≥2 hours per week of MSA was associated with lower all-cause mortality, independent of aerobic activity. Reasons for the lack of association with higher amounts of MSA are unclear. Our findings support recommending muscle-strengthening activities for overall health.
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http://dx.doi.org/10.5888/pcd17.190408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417019PMC
August 2020

Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium.

Cancer Epidemiol Biomarkers Prev 2020 10 30;29(10):2010-2018. Epub 2020 Jul 30.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites.

Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests.

Results: Most associations did not vary by tumor site ( ≥ 0.05). Associations between first pregnancy ( = 0.04), tubal ligation ( = 0.01), and early-adult (age 18-21 years) body mass index (BMI; = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer ( = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases.

Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site.

Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541500PMC
October 2020

American Cancer Society guideline for diet and physical activity for cancer prevention.

CA Cancer J Clin 2020 07 9;70(4):245-271. Epub 2020 Jun 9.

Cancer Control, American Cancer Society, Atlanta, Georgia.

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.
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http://dx.doi.org/10.3322/caac.21591DOI Listing
July 2020
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