Publications by authors named "Edward Giovannucci"

1,223 Publications

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Genetic Obesity Variants and Risk of Conventional Adenomas and Serrated Polyps.

Dig Dis Sci 2021 Aug 17. Epub 2021 Aug 17.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Higher body mass index (BMI) is associated with increased risk of colorectal cancer. How genetically predicted BMI may be associated with colorectal cancer precursors is unknown.

Aims: Our objective was to quantify the association of genetically predicted and measured BMI with risk of colorectal cancer precursors.

Methods: We evaluated the association of genetically predicted and measured BMI with risk of conventional adenomas, serrated polyps, and synchronous polyps among 27,426 participants who had undergone at least one lower gastrointestinal endoscopy in the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study. Genetic risk score was derived from 97 BMI-related single nucleotide polymorphisms. Multivariable logistic regression evaluated each polyp subtype compared to non-polyps.

Results: For conventional adenomas, the OR per 2-kg/m increase was 1.03 (95% CI, 1.01-1.04) for measured BMI and 0.98 (95% CI, 0.88-1.10) for genetically predicted BMI; for serrated polyps, the OR was 1.06 (95% CI, 1.04-1.08) and 1.04 (95% CI, 0.90-1.20), respectively; for synchronous polyps, the OR was 1.10 (95% CI, 1.07-1.13) and 1.09 (95% CI, 0.89-1.34), respectively. Genetically predicted BMI was associated with synchronous polyps in women (OR = 1.37, 95% CI: 1.05-1.79).

Conclusion: Genetically predicted BMI was not associated with colorectal cancer precursor lesions. The confidence intervals were wide and encompassed those for measured BMI, indicating that null findings may be due to insufficient power.
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http://dx.doi.org/10.1007/s10620-021-07193-xDOI Listing
August 2021

Potential Impact of Time Trend of Lifestyle Risk Factors on Burden of Major Gastrointestinal Cancers in China.

Gastroenterology 2021 Aug 10. Epub 2021 Aug 10.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts.

Background & Aims: China has the largest number of liver, esophageal, and gastric cancer incidence and the second highest colorectal cancer incidence in 2020. Examining the time trend of relevant lifestyle risk factors would help project the trend of these gastrointestinal (GI) cancer incidence in China.

Methods: We estimated the time trend of the lifestyle factors based on the China Health and Nutrition Survey 1991 to 2011. We applied the comparative risk assessment method to estimate the population attributable fraction of GI cancers attributable to each risk factor. We also projected the prevalence of lifestyle factors and the associated burden of GI cancer from 2011 to 2031.

Results: In 2011, 56.5% of colorectal, 59.8% of gastric, 48.5% of esophageal, and 35.2% of liver cancer in China were attributable to the lifestyle risk factors under study. Smoking, sodium intake, low vegetable intake, and low fruit intake have improved over time but remained far from optimal and are expected to be responsible for 170,000, 35,000, 22,000, and 50,000 GI cancer cases in 2031, respectively. High body mass index, red and processed meat consumption, and low physical activity are expected to contribute increasingly more GI cancer, accounting for 142,000, 185,000, 60,000, and 53,000 cases in 2031, respectively. The estimated population attributable fraction for all risk factors in 2031 is 52.1%.

Conclusions: Lifestyle risk factors have had an impact on the risk of GI cancer in China, and the impact is projected to increase. If everyone could adhere to the optimal lifestyle, half of all GI cancer events would be prevented by year 2031.
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http://dx.doi.org/10.1053/j.gastro.2021.08.006DOI Listing
August 2021

Adolescent Plant Product Intake in Relation to Later Prostate Cancer Risk and Mortality in the NIH-AARP Diet and Health Study.

J Nutr 2021 Aug 12. Epub 2021 Aug 12.

Division of Public Health Sciences, Department of Surgery, and the Alvin J Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA.

Background: Although fruit and vegetable intake during adolescence, a potentially sensitive time period for prostate cancer (PCa) development, has been proposed to protect against PCa risk, few studies have investigated the role of adolescent plant product intake in PCa development.

Methods: Intake of various vegetables, fruit, and grains by males at ages 12-13 y was examined in relation to later PCa risk and mortality in the NIH-AARP Diet and Health Study. Cox proportional hazards regression was used to calculate HRs and 95% CIs of nonadvanced (n = 14,238) and advanced (n = 2,170) PCa incidence and PCa mortality (n = 760) during 1,729,896 person-years of follow-up.

Results: None of the plant products examined were associated consistently with all PCa outcomes. However, greater adolescent intakes of tomatoes (P-trend = 0.004) and nonstarch vegetables (P-trend = 0.025) were associated with reduced risk of nonadvanced PCa, and greater intakes of broccoli (P-trend = 0.050) and fruit juice (P-trend = 0.019-0.025) were associated with reduced risk of advanced PCa and/or PCa mortality. Positive trends were also observed for greater intakes of fruit juice (P-trend = 0.002), total fruit (P-trend = 0.014), and dark bread (P-trend = 0.035) with nonadvanced PCa risk and for greater intakes of legumes (P-trend < 0.001), fiber (P-trend = 0.001), and vegetable protein (P-trend = 0.013-0.040) with advanced PCa risk or PCa mortality.

Conclusions: Our findings do not provide strong evidence to suggest that adolescent plant product intake is associated with reduced PCa risk.
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http://dx.doi.org/10.1093/jn/nxab241DOI Listing
August 2021

Reply to Yi M et al.

Adv Nutr 2021 07;12(4):1595-1596

Division of Pediatric Nephrology, Severance Children's Hospital, Seoul, Republic of Korea.

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http://dx.doi.org/10.1093/advances/nmab043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321832PMC
July 2021

Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study.

Br J Sports Med 2021 Jul 22. Epub 2021 Jul 22.

Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Purpose: To determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea.

Methods: Data regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020.

Results: Out of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500-1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses.

Conclusion: Adults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.
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http://dx.doi.org/10.1136/bjsports-2021-104203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300550PMC
July 2021

Unrestrained eating behavior and risk of digestive system cancers: a prospective cohort study.

Am J Clin Nutr 2021 Jul 22. Epub 2021 Jul 22.

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

Background: Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse.

Objectives: We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk.

Methods: Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers.

Results: During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non-statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite.

Conclusions: Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted.
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http://dx.doi.org/10.1093/ajcn/nqab235DOI Listing
July 2021

The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.

Gastroenterology 2021 Jul 14. Epub 2021 Jul 14.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Electronic address:

Background & Aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (HS), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking.

Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (OR, 1.31; 95% CI, 1.10-1.56, P = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (OR, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; P = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50.

Conclusions: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.
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http://dx.doi.org/10.1053/j.gastro.2021.07.008DOI Listing
July 2021

Adherence to the World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and Colorectal Cancer Survival.

Cancer Epidemiol Biomarkers Prev 2021 Jul 16. Epub 2021 Jul 16.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background: Patients with cancer are recommended to follow cancer prevention guidelines due to inadequate evidence for specific recommendations for cancer survivors.

Methods: We examined whether diet and lifestyle scores measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention guidelines were associated with colorectal cancer-specific and overall mortality among 1,491 patients with colorectal cancer in two prospective cohorts. Cox proportional hazards regression models were used to calculate the multivariable-adjusted HRs and 95% confidence intervals (CI).

Results: During a median follow-up of 7.92 years, there were 641 deaths (179 colorectal cancer-specific deaths). Patients in the highest quartile of the post-diagnostic WCRF/AICR lifestyle score including diet, body mass index (BMI), and physical activity had a 24% lower risk (HR = 0.76, 95% CI: 0.49-1.18) of colorectal cancer-specific mortality and a 37% lower risk (HR = 0.63, 95% CI: 0.50-0.78) of overall mortality compared with the lowest quartile. When BMI was not included in the lifestyle score due to potential disease-related weight loss, stronger inverse associations were observed for both colorectal cancer-specific and overall mortality for the same comparison (colorectal cancer-specific: HR = 0.50, 95% CI: 0.32-0.79; overall: HR = 0.59, 95% CI: 0.47-0.75). The post-diagnostic WCRF/AICR diet score was not statistically significantly associated with either colorectal cancer-specific or overall mortality.

Conclusions: Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with improved survival in patients with colorectal cancer.

Impact: This study provides support for patients with colorectal cancer to follow cancer prevention recommendations after diagnosis. Future studies on cancer survivors will continue to contribute to evidence-based diet and lifestyle recommendations for patients with cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0120DOI Listing
July 2021

Prenatal and Perinatal Factors and Risk of Cancer in Middle and Older Adulthood among Men.

Cancer Epidemiol Biomarkers Prev 2021 Jul 16. Epub 2021 Jul 16.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background: Prenatal factors have been associated with risk of cancers later in life, although studies in men have largely been case-control and focused on birth size only.

Methods: We used data from 5,845 men in the Health Professionals Follow-up Study (HPFS) to prospectively examine associations between several prenatal and perinatal factors and incident adult cancer risk. In 1994, mothers of participants reported information on characteristics and behaviors related to their pregnancy with their sons. We used multivariable Cox proportional hazards models to calculate HRs and 95% confidence intervals (CI) of associations between prenatal and perinatal risk factors and cancer risk.

Results: During 20 years of follow-up, 1,228 incident cases of overall cancer were documented. Men with a birth weight of ≥4 kg had a 21% increased risk of overall cancer (HR, 1.21; 95% CI, 1.02-1.43) compared with those with a birth weight of 2.5 to 3.9 kg. Greater weight gain during pregnancy (>13.6 kg vs. 6.8-8.6 kg) was also associated with a higher risk of overall cancer (HR, 1.22; 95% CI, 1.02-1.46), and was stronger for men whose mothers had a prepregnancy BMI<21 kg/m (HR, 1.30; 95% CI, 1.00-1.67) compared with body mass index (BMI) ≥21 kg/m (HR, 1.14; 95% CI, 0.85-1.51). There was no association between maternal age and overall cancer risk.

Conclusions: Higher birth weight and maternal weight gain are associated with increased cancer risk in adult men.

Impact: Our findings support the hypothesis that the environment plays a role in the etiology of cancer in middle and older adulthood.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0316DOI Listing
July 2021

Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival.

Br J Cancer 2021 Jul 15. Epub 2021 Jul 15.

Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Background: The influence of a high sugar diet on colorectal cancer (CRC) survival is unclear.

Methods: Among 1463 stage I-III CRC patients from the Nurses' Health Study and Health Professionals Follow-up Study, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in relation to intake of post-diagnosis sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), fruit juice, fructose and other sugars.

Results: Over a median 8.0 years, 781 cases died (173 CRC-specific deaths). Multivariable-adjusted HRs for post-diagnosis intake and CRC-specific mortality were 1.21 (95% CI: 0.87-1.68) per 1 serving SSBs per day (serving/day) and 1.24 (95% CI: 0.95-1.63) per 20 grams fructose per day. Significant positive associations for CRC-specific mortality were primarily observed ≤5 years from diagnosis (HR per 1 serving/day of SSBs = 1.59, 95% CI: 1.06-2.38). Significant inverse associations were observed between ASBs and CRC-specific and all-cause mortality (HR for ≥5 versus <1 serving/week = 0.44, 95% CI: 0.26-0.75 and 0.70, 95% CI: 0.55-0.89, respectively).

Conclusions: Higher post-diagnosis intake of SSBs and sugars may be associated with higher CRC-specific mortality, but only up to 5 years from diagnosis, when more deaths were due to CRC. The inverse association between ASBs and CRC-specific mortality warrants further examination.
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http://dx.doi.org/10.1038/s41416-021-01487-7DOI Listing
July 2021

Adiposity, Adulthood Weight Change, and Risk of Incident Hepatocellular Carcinoma.

Cancer Prev Res (Phila) 2021 Jul 15. Epub 2021 Jul 15.

Harvard Medical School, Boston, Massachusetts.

Prospective data are limited regarding dynamic adulthood weight changes and hepatocellular carcinoma (HCC) risk. We included 77,238 women (1980-2012) and 48,026 men (1986-2012), who recalled young-adult weight [age 18 years (women); 21 years (men)], and provided biennially updated information regarding weight, body mass index (BMI), and comorbidities. Overall adulthood weight change was defined as the difference in weight (kilograms) between young-adulthood and present. Using Cox proportional hazards models, we calculated multivariable adjusted HRs (aHR) and 95% confidence intervals (CI). Over 3,676,549 person-years, we documented 158 incident HCC cases. Elevated HCC risk was observed with higher BMI in both young-adulthood and later-adulthood [continuous aHRs per each 1 unit = 1.05; 95% CI = 1.02-1.09 ( = 0.019), and 1.08; 95% CI = 1.06-1.10 ( = 0.004), respectively]. Moreover, overall adulthood weight gain was also significantly associated with increased HCC risk (aHR per each 1-kg increase = 1.03; 95% CI = 1.01-1.08; = 0.010), including after further adjusting for young-adult BMI ( = 0.010) and later-adult BMI ( = 0.008). Compared with adults with stable weight (±5 kg), the multivariable-aHRs with weight gain of 5-<10 kg, 10-<20 kg, and ≥20 kg were, 1.40 (95% CI = 0.67-2.16), 2.09 (95% CI = 1.11-3.95), and 2.61 (95% CI = 1.42-5.22), respectively. In two prospective, nationwide cohorts, adulthood weight gain was significantly associated with increased HCC risk. PREVENTION RELEVANCE: Our data suggest that maintaining a stable weight during adulthood, specifically by preventing weight gain, could represent an important public health strategy for the prevention of hepatocellular carcinoma.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0549DOI Listing
July 2021

Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies.

Am J Clin Nutr 2021 Jul 13. Epub 2021 Jul 13.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Background: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis.

Objectives: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC.

Methods: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs.

Results: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association.

Conclusions: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.
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http://dx.doi.org/10.1093/ajcn/nqab217DOI Listing
July 2021

Changes in Lifestyle Factors After Endoscopic Screening: A Prospective Study in the United States.

Clin Gastroenterol Hepatol 2021 Jul 10. Epub 2021 Jul 10.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Endoscopic screening and adherence to a healthy lifestyle are major avenues for colorectal cancer (CRC) prevention. We investigated changes in lifestyles after endoscopic screening.

Methods: We drew data from 76,303 pairs of time- and age-matched individuals who had and had not, respectively, reported first time endoscopic screening, in the 3 cohorts (Nurses' Health Study I and II and the Health Professionals Follow-up Study). Detailed information was collected every 2-4 years on endoscopy screening, 12 lifestyle factors (including smoking, physical activity, regular use of aspirin/nonsteroidal anti-inflammatory drugs, body weight, and 8 dietary factors), and adherence to a healthy lifestyle based on a score defined by 5 major lifestyle factors (smoking, alcohol, body weight, physical activity, and diet). We assessed changes in lifestyle from pre- to post-screening periods for the matched pairs. We also conducted subgroup analysis according to screening findings (negative, low- and high-risk polyps, and CRC).

Results: Endoscopic screening was associated with higher prevalence of adherence to a healthy lifestyle (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.16). The association strengthened with the severity of the screening findings, with an OR of 1.09 (95% CI, 1.03-1.15) for negative screening, 1.19 (95% CI, 1.07-1.33) for low-risk polyps, 1.42 (95% CI, 1.14-1.77) for high-risk polyps, and 1.55 (95% CI, 1.17-2.05) for CRC. The individual lifestyle factors and diet showed modest change.

Conclusions: Endoscopic screening was associated with a modest improvement in healthy lifestyles, particularly in individuals with more severe endoscopic findings. Further efforts of integrating lifestyle medicine into the screening setting are needed, to better leverage the teachable moment in improving CRC prevention.
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http://dx.doi.org/10.1016/j.cgh.2021.07.014DOI Listing
July 2021

Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.

Gastroenterology 2021 Jul 7. Epub 2021 Jul 7.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

Background & Aims: Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50.

Methods: We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model.

Results: We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878).

Conclusions: In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.
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http://dx.doi.org/10.1053/j.gastro.2021.07.002DOI Listing
July 2021

Obesity, Adiposity, and Risk of Symptomatic Gallstone Disease According to Genetic Susceptibility.

Clin Gastroenterol Hepatol 2021 Jul 2. Epub 2021 Jul 2.

Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background & Aims: Adiposity has been consistently associated with gallstone disease risk. We aimed to characterize associations of anthropometric measures (body mass index [BMI], recent weight change, long-term weight change, waist circumference, and waist-to-hip ratio) with symptomatic gallstone disease according to strata of gallstone disease polygenic risk score (PRS).

Methods: We conducted analysis among 34,626 participants with available genome-wide genetic data within 3 large, prospective, U.S. cohorts-the Nurses' Health Study (NHS), Health Professionals Follow-Up Study, and NHS II. We characterized joint associations of PRS and anthropometric measures and tested for interactions on the relative and absolute risk scales.

Results: Women in the highest BMI and PRS categories (BMI ≥30 kg/m and PRS ≥1 SD above mean) had odds ratio for gallstone disease of 5.55 (95% confidence interval, 5.29 to 5.81) compared with those in the lowest BMI and PRS categories (BMI <25 kg/m and PRS <1 SD below the mean). The corresponding odds ratio among men was 1.65 (95% confidence interval, 1.02 to 2.29). Associations for BMI did not vary within strata of PRS on the relative risk scale. On the absolute risk scale, the incidence rate difference between obese and normal-weight individuals was 1086 per 100,000 person-years within the highest PRS category, compared with 666 per 100,000 person-years in the lowest PRS category, with strong evidence for interaction with the ABCG8 locus.

Conclusions: While maintenance of a healthy body weight reduces gallstone disease risk among all individuals, risk reduction is higher among the subset with greater genetic susceptibility to gallstone disease.
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http://dx.doi.org/10.1016/j.cgh.2021.06.044DOI Listing
July 2021

Associations between body shape across the life course and adulthood concentrations of sex hormones in men and pre- and postmenopausal women: a multicohort study.

Br J Nutr 2021 Jun 30:1-10. Epub 2021 Jun 30.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

The objective was to investigate associations between life-course adiposity and sex hormone concentrations: trajectory of adiposity from age 5 to 40 (premenopausal)/60 (postmenopausal women and men) in relation to levels of oestrone (E1), oestradiol (E2), sex hormone-binding globulins (SHBG), testosterone in 4801 premenopausal and 6019 postmenopausal women in the Nurses' Health Study (NHS) and NHS II, and 2431 men in the Health Professionals Follow-up Study. We used group-based trajectory models to identify groups within each cohort based on recalled somatotypes and reported BMI. Multivariate linear regression models were used to compare sex hormone concentration across different trajectory groups. The mean age at blood draw was 64·1 ± 8·1 years for men, 59·4 ± 6·0 for postmenopausal and 44·1 ± 4·6 for premenopausal women. In men, compared with the medium-stable group, lean-marked increase and medium increase groups had lower levels of SHBG (percentage difference: -17 and -9 %) and testosterone (-15 and -13 %). In postmenopausal women, compared with the medium-stable group, lean-marked increase and medium increase groups had higher levels of E1 (21 and 34 %) and E2 (45 and 68 %) but lower level of SHBG (-29 and -35 %). In premenopausal women, compared with the lean-moderate increase group, medium-stable/increase and heavy-stable/increase groups had lower levels of SHBG (-6 and -28 %). Attained adulthood adiposity and middle-life weight gain were associated with lower SHBG and testosterone in men, higher E1 and E2 and lower SHBG in postmenopausal women, and lower SHBG in premenopausal women. The study indicates the importance of maintaining a healthy body weight throughout life course for homoeostasis of sex hormones.
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http://dx.doi.org/10.1017/S0007114521001732DOI Listing
June 2021

Economic burden of colorectal and breast cancers attributable to lack of physical activity in Brazil.

BMC Public Health 2021 06 22;21(1):1190. Epub 2021 Jun 22.

Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Background: The increasing number of cancer patients has an escalating economic impact to public health systems (approximately, International dollars- Int$ 60 billion annually in Brazil). Physical activity is widely recognized as one important modifiable risk factor for cancer. Herein, we estimated the economic costs of colon and post-menopausal breast cancers in the Brazilian Unified Health System (SUS) attributable to lack of physical activity.

Methods: Population attributable fractions were calculated using prevalence data from 57,962 adults who answered a physical activity questionnaire in the Brazilian National Health Survey, and relative risks of colon and breast cancer from a meta-analysis. Annual costs (1 Int$ = 2.1 reais) with hospitalization, chemotherapy and radiotherapy were obtained from the Hospital and Ambulatory Information Systems of the Brazilian SUS. Two counterfactual scenarios were considered: theoretical minimum risk exposure level (≥8000 MET-min/week) and physical activity guidelines (≥600 MET-min/week).

Results: Annually, the Brazilian SUS expended Int$ 4.5 billion in direct costs related to cancer treatment, of which Int$ 553 million due to colon and breast cancers. Direct costs related to colon and breast cancers attributable to lack of physical activity were Int$ 23.4 million and Int$ 26.9 million, respectively. Achieving at least the physical activity guidelines would save Int$ 10.3 mi (colon, Int$ 6.4 mi; breast, Int$ 3.9 mi).

Conclusions: Lack of physical activity accounts for Int$ 50.3 million annually in direct costs related to colon and post-menopausal breast cancers. Population-wide interventions aiming to promote physical activity are needed to reduce the economic burden of cancer in Brazil.
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http://dx.doi.org/10.1186/s12889-021-11221-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220697PMC
June 2021

Discovery and Features of an Alkylating Signature in Colorectal Cancer.

Cancer Discov 2021 Jun 17. Epub 2021 Jun 17.

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.

Several risk factors have been established for colorectal cancer, yet their direct mutagenic effects in patients' tumors remain to be elucidated. Here, we leveraged whole-exome sequencing data from 900 colorectal cancer cases that had occurred in three U.S.-wide prospective studies with extensive dietary and lifestyle information. We found an alkylating signature that was previously undescribed in colorectal cancer and then showed the existence of a similar mutational process in normal colonic crypts. This alkylating signature is associated with high intakes of processed and unprocessed red meat prior to diagnosis. In addition, this signature was more abundant in the distal colorectum, predicted to target cancer driver mutations p.G12D, p.G13D, and p.E545K, and associated with poor survival. Together, these results link for the first time a colorectal mutational signature to a component of diet and further implicate the role of red meat in colorectal cancer initiation and progression. SIGNIFICANCE: Colorectal cancer has several lifestyle risk factors, but the underlying mutations for most have not been observed directly in tumors. Analysis of 900 colorectal cancers with whole-exome sequencing and epidemiologic annotations revealed an alkylating mutational signature that was associated with red meat consumption and distal tumor location, as well as predicted to target p.G12D/p.G13D.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1656DOI Listing
June 2021

Dietary fiber intake, the gut microbiome, and chronic systemic inflammation in a cohort of adult men.

Genome Med 2021 Jun 17;13(1):102. Epub 2021 Jun 17.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Background: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

Methods: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of C-reactive protein (CRP), an established biomarker for chronic inflammation. Data were analyzed using multivariate linear mixed models.

Results: We found that inflammation-associated gut microbial configurations corresponded with higher CRP levels. A greater intake of dietary fiber was associated with shifts in gut microbiome composition, particularly Clostridiales, and their potential for carbohydrate utilization via polysaccharide degradation. This was particularly true for fruit fiber sources (i.e., pectin). Most striking, fiber intake was associated with significantly greater CRP reduction in individuals without substantial Prevotella copri carriage in the gut, whereas those with P. copri carriage maintained stable CRP levels regardless of fiber intake.

Conclusions: Our findings offer human evidence supporting a fiber-gut microbiota interaction, as well as a potential specific mechanism by which gut-mediated systemic inflammation may be mitigated.
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http://dx.doi.org/10.1186/s13073-021-00921-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212460PMC
June 2021

Adolescent animal product intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study.

Br J Cancer 2021 Jun 16. Epub 2021 Jun 16.

Division of Public Health Sciences, Department of Surgery; and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.

Background: Adolescent intake of animal products has been proposed to contribute to prostate cancer (PCa) development because of its potentially carcinogenic constituents and influence on hormone levels during adolescence.

Methods: We used data from 159,482 participants in the NIH-AARP Diet and Health Study to investigate associations for recalled adolescent intake of red meat (unprocessed beef and processed red meat), poultry, egg, canned tuna, animal fat and animal protein at ages 12-13 years with subsequent PCa risk and mortality over 14 years of follow-up. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total (n = 17,349), advanced (n = 2,297) and fatal (n = 804) PCa.

Results: Suggestive inverse trends were observed for adolescent unprocessed beef intake with risks of total, advanced and fatal PCa (multivariable-adjusted P-trends = 0.01, 0.02 and 0.04, respectively). No consistent patterns of association were observed for other animal products by PCa outcome.

Conclusion: We found evidence to suggest that adolescent unprocessed beef intake, or possibly a correlate of beef intake, such as early-life socioeconomic status, may be associated with reduced risk and mortality from PCa. Additional studies with further early-life exposure information are warranted to better understand this association.
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http://dx.doi.org/10.1038/s41416-021-01463-1DOI Listing
June 2021

The critical need for guidance in managing glycaemic control in patients with cancer.

Diabet Med 2021 Jun 16:e14624. Epub 2021 Jun 16.

Harvard T.H. Chan School of Public Health, Nutrition Department, Boston, MA, USA.

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http://dx.doi.org/10.1111/dme.14624DOI Listing
June 2021

Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database.

JAMA Netw Open 2021 Jun 1;4(6):e2112539. Epub 2021 Jun 1.

Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.

Importance: While increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC.

Objective: To characterize the overall survival for individuals with early-onset CRC.

Design, Setting, And Participants: This cohort study used data from the National Cancer Database. Included individuals were ages 0 to 90 years and diagnosed with primary CRC from January 1, 2004, through December 31, 2015. Individuals diagnosed at ages 51 through 55 years were selected as the reference group and defined as later-onset CRC for this study. Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at that age in our population, given that these individuals disproportionately presented with earlier stage. All statistical analyses were conducted from January 4, 2020, through December 26, 2020.

Exposures: Early-onset CRC was defined as age younger than 50 years at diagnosis.

Main Outcomes And Measures: Overall survival was assessed by Kaplan-Meier analysis and Cox proportional hazards regression.

Results: Among 769 871 individuals with CRC (377 890 [49.1%] women; 636 791 White individuals [82.7%]), 353 989 individuals (46.0%) died (median [range] follow-up: 2.9 [0-14.0] years), 102 168 individuals (13.3%) had early-onset CRC, and 78 812 individuals (10.2%) had later-onset CRC. Individuals with early-onset CRC, compared with those diagnosed with CRC at ages 51 through 55 years, had a lower 10-year survival rate (53.6% [95% CI, 53.2%-54.0%] vs 54.3% [95% CI, 53.8%-54.8%]; P < .001) in unadjusted analysis. However, after adjustment for other factors associated with mortality, most notably stage, individuals with early-onset CRC had a lower risk of death compared with individuals diagnosed from ages 51 through 55 years (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93-0.96]; P < .001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88-0.90; P < .001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84-0.92]; P < .001) and stages I (adjusted HR, 0.87 [95% CI, 0.81-0.93]; P < .001) and II (adjusted HR, 0.86 [95% CI, 0.82-0.90]; P < .001) and was absent among those diagnosed at ages 25 years or younger and stages III through IV.

Conclusions And Relevance: These findings suggest that there is a survival benefit for individuals with early-onset CRC compared with those diagnosed with CRC at later ages. Further study is needed to understand the underlying heterogeneity of survival among individuals with early-onset CRC by age and stage.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.12539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209612PMC
June 2021

Muscle-strengthening activities and risk of cardiovascular disease, type 2 diabetes, cancer and mortality: A review of prospective cohort studies.

J Intern Med 2021 Oct 2;290(4):789-805. Epub 2021 Jul 2.

Departments of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

The benefits of aerobic moderate-to-vigorous physical activity (MVPA) on major non-communicable diseases (NCDs) are well established. However, much less is known whether muscle-strengthening activities (i.e., resistance/weight/strength training) confer similar benefits. Herein, we conducted a narrative literature review and summarized the existing evidence from large prospective cohort studies on muscle strengthening activities and risk of major chronic diseases and mortality in adults generally free of major NCDs at baseline. Current epidemiologic evidence suggests that engagement in muscle-strengthening activities over 1-2 sessions (or approximately 60-150 min) per week was associated with reduced risk of cardiovascular disease (seven studies; approximately 20%-25% reduction), type 2 diabetes (four studies; approximately 30% reduction), cancer mortality (four studies; approximately 15%-20% reduction) as well as all-cause mortality (six studies; approximately 20%-25% reduction). For diabetes, the risk appears to lower further with even higher levels of muscle-strengthening activities, but some studies for cardiovascular and all-cause mortality suggest a reversal whereby higher levels (≥2.5 h/week) have less benefit, or are even harmful, relative to lower levels of activity. The likely mechanisms contributing to a benefit include improvement in body composition, lipid profile, insulin resistance and inflammation. The evidence supports engaging in 1-2 sessions (up to 2.5 h) per week, preferably performed complementary to the recommended levels of aerobic MVPA. Although data are limited, caution is suggested for training exceeding 2.5 h per week. Further studies are required to better understand the influence of frequency, duration and intensity of muscle-strengthening activities on major NCDs and mortality in diverse populations.
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http://dx.doi.org/10.1111/joim.13344DOI Listing
October 2021

Can there be consensus on whether vasectomy is a prostate cancer risk factor?

Prostate Cancer Prostatic Dis 2021 Jun 9. Epub 2021 Jun 9.

Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1038/s41391-021-00400-wDOI Listing
June 2021

Association between weight cycling and risk of kidney cancer: a prospective cohort study and meta-analysis of observational studies.

Cancer Causes Control 2021 Sep 5;32(9):1029-1038. Epub 2021 Jun 5.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Purpose: Weight cycling is common in populations. However, it is unclear whether frequency and magnitude of weight cycling is associated with kidney cancer risk, independent of body mass index (BMI).

Methods: A prospective cohort study followed 85,562 participants from Health Professionals Follow-up Study and Nurses' Health Study (1992-2014). At baseline, participants reported frequency and magnitude of intentional weight loss in the past 4 years. Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We also conducted a meta-analysis of all available observational studies including our two cohorts.

Results: During 22 years of follow-up, we identified 441 kidney cancer cases. Compared with non-weight cyclers (no attempt of intentional weight loss), severe cyclers (≥ 3 times of intentional weight loss of ≥ 4.5 kg) were at increased kidney cancer risk after adjusting for BMI before weight cycling (pooled multivariable-adjusted HR, 1.78; 95% CI, 1.19, 2.66). Additional adjustment for attained BMI after weight cycling had minimal influence. There was a positive trend between weight cycling by frequency and magnitude and kidney cancer risk (P-trend = 0.01). Moreover, the observed positive association did not differ by subtypes of cyclers (e.g., adiposity status, weight-loss methods). In the meta-analysis, we found a strong positive association between weight cycling and kidney cancer risk (summary relative risk for weight cyclers vs. non-cyclers, 1.51; 95% CI, 1.16, 1.96; I: 52.2%; 6 studies).

Conclusion: Frequent substantial weight cycling was associated with increased risk of kidney cancer, independent of BMI. Our study suggests that weight cycling may be an important risk factor for kidney cancer.
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http://dx.doi.org/10.1007/s10552-021-01455-9DOI Listing
September 2021

Has COVID-19 Affected Cancer Screening Programs? A Systematic Review.

Front Oncol 2021 17;11:675038. Epub 2021 May 17.

School of Public Health, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Background: Health care services across the world have been enormously affected by the onset of the coronavirus disease 2019 (COVID-19). Services in oncology have been curtailed because medical services have been focused on preventing the spread of the virus and maximizing the number of available hospital beds. The present study was designed to investigate the impact of COVID-19 on cancer screening.

Methods: Databases such as Medline, Web of Science Core Collection (Indexes = SCI-EXPANDED, SSCI, A & HCI Timespan) and Scopus were searched comprehensively for articles published until January 2021. The keywords used were COVID-19 and , Articles dealing with cancer screening in the COVID-19 pandemic were included in the review.

Results: The review comprised 17 publications. The impact of COVID-19 was categorized into four dimensions: a significant decline in cancer screening and pathology samples, the cancer diagnosis rate, an increase in advanced cancers, mortality rate and years of life lost (YLLs).

Conclusion: Cancer screening programs have been clearly interrupted since the onset of the COVID-19 disease. The anticipated outcomes include delayed diagnosis and marked increases in the numbers of avoidable cancer deaths. Urgent policy interventions are needed to handle the backlog of routine diagnostic services and minimize the harmful effects of the COVID-19 pandemic on cancer patients.
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http://dx.doi.org/10.3389/fonc.2021.675038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165307PMC
May 2021

Muscle-strengthening activities and cancer incidence and mortality: a systematic review and meta-analysis of observational studies.

Int J Behav Nutr Phys Act 2021 05 29;18(1):69. Epub 2021 May 29.

Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina Preventiva, São Paulo, SP, Brazil.

Background: Physical activity has been associated with reduced risk of seven types of cancer. It remains unclear, however, whether muscle-strengthening activities also reduce cancer incidence and mortality.

Methods: PubMed, Embase, Web of Science and Scopus were searched from inception to March 2020. Summary hazard ratio (HR) and 95% confidence intervals (CI) were estimated using random-effects models.

Results: Twelve studies (11 cohorts; 1 case-control), 6 to 25 years of follow-up, including 1,297,620 participants, 32,196 cases and 31,939 deaths, met inclusion criteria. Muscle-strengthening activities were associated with a 26% lower incidence of kidney cancer (HR for high vs low levels of muscle-strengthening activities: 0.74; 95% CI 0.56 to 0.98; I 0%; 2 studies), but not with incidence of other 12 types of cancer. Muscle-strengthening activities were associated with lower total cancer mortality: HRs for high vs low levels of muscle-strengthening activities was 0.87 (95% CI 0.73 to 1.02; I 58%; 6 studies); and HR for ≥2 times/week vs < 2 times/week of muscle-strengthening activities was 0.81 (95% CI 0.74 to 0.87; I 0%; 4 studies). Regarding the weekly duration of muscle-strengthening activities, HR for total cancer mortality were 0.91 (95% CI 0.82 to 1.01; I 0%; 2 studies) for 1-59 min/week and 0.98 (95% CI 0.89 to 1.07; I 0%) for ≥60 min/week vs none. Combined muscle-strengthening and aerobic activities (vs none) were associated with a 28% lower total cancer mortality (HR 0.72; 95% CI 0.53 to 0.98; I 85%; 3 studies).

Conclusions: Muscle-strengthening activities were associated with reduced incidence of kidney cancer and total cancer mortality. Combined muscle-strengthening and aerobic activities may provide a greater reduction in total cancer mortality.
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http://dx.doi.org/10.1186/s12966-021-01142-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164763PMC
May 2021

Association of bowel movement frequency and laxative use with risk of hepatocellular carcinoma in US women and men.

Int J Cancer 2021 10 4;149(8):1529-1535. Epub 2021 Jun 4.

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

Abnormal bowel movements have been related to a variety of hepatocellular carcinoma (HCC) risk factors such as dyslipidemia, diabetes and altered metabolism of bile acids and gut microbiota. However, little is known about whether bowel movement frequency affects the risk of developing HCC. We followed 88 123 women in the Nurses' Health Study (NHS) and 28 824 men in the Health Professionals Follow-up Study (HPFS) for up to 24 years. The Cox proportional hazards regression model was used to calculate multivariable hazard ratios (HRs) and confidence intervals (95%CI). We documented 101 incident HCC cases. Compared to those with daily bowel movements, participants with bowel movement more than once per day had a multivariable HR of 1.93 (95%CI: 1.18 to 3.16) in the pooled cohorts. For the same comparison, the positive association appeared stronger for men (2.72, 95% CI: 1.14 to 6.44) than for women (1.63, 95% CI: 0.87 to 3.06) but there was no statistically significant heterogeneity by sex (P-value = .31). We found null associations between bowel movement every 2 days or less and the risk of HCC (HR = 1.05, 95%CI: 0.62 to 1.79). The HR (95%CI) for participants who used laxatives regularly relative to those who never used laxatives was 1.00 (0.64 to 1.55). Our results suggest participants with bowel movement more than once daily is associated with a higher risk of developing HCC compared to those with daily bowel movements. These findings need to be confirmed and potential mechanisms underlying this association need to be elucidated.
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http://dx.doi.org/10.1002/ijc.33699DOI Listing
October 2021

The Role of Mendelian Randomization Studies in Deciphering the Effect of Obesity on Cancer.

J Natl Cancer Inst 2021 May 21. Epub 2021 May 21.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Associations of obesity have been established for at least 11 cancer sites in observational studies, though some questions remain as to causality, strength of associations, and timing of associations throughout the life course. In recent years, Mendelian randomization (MR) has provided complementary information to traditional approaches, but the validity requires that the genetic instrumental variables be causally related to cancers only mediated by the exposure. We summarize and evaluate existing evidence from MR studies in comparison with conventional observational studies to provide insights into the complex relationship between obesity and multiple cancers. MR studies further establish the causality of adult obesity with esophageal adenocarcinoma, cancers of the colorectum, endometrium, ovary, kidney, and pancreas, as well as the inverse association of early life obesity with breast cancer. MR studies, which might account for lifelong adiposity, suggest that the associations in observational studies typically based on single measurement may underestimate the magnitude of the association. For lung cancer, MR studies find a positive association with obesity, supporting that the inverse association observed in some conventional observational studies likely reflects reverse causality (loss of lean body mass before diagnosis) and confounding by smoking. However, MR studies have not had sufficient power for gallbladder cancer, gastric cardia cancer, and multiple myeloma. In addition, more MR studies are needed to explore the effect of obesity at different time points on postmenopausal breast cancer and aggressive prostate cancer.
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http://dx.doi.org/10.1093/jnci/djab102DOI Listing
May 2021

Association of Screening Lower Endoscopy With Colorectal Cancer Incidence and Mortality in Adults Older Than 75 Years.

JAMA Oncol 2021 Jul;7(7):985-992

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Evidence indicates that screening for colorectal cancer (CRC) beginning at 50 years of age can detect early-stage CRC and premalignant neoplasms (eg, adenomas) and thus prevent CRC-related mortality. At present, the US Preventive Services Task Force recommends continuing CRC screening until 75 years of age and individualized decision-making for adults older than 75 years, while accounting for a patient's overall health and screening history. However, scant data exist to support these recommendations.

Objective: To examine the association of lower gastrointestinal tract screening endoscopy with the risk of CRC incidence and CRC-related mortality in older US adults.

Design, Setting, And Participants: This prospective cohort study of health care professionals in the US included data from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) from January 1, 1988, through January 31, 2016, for the HPFS and June 30, 2016, for the NHS. Data were analyzed from May 8, 2019, to July 9, 2020.

Exposures: History of screening sigmoidoscopy or colonoscopy (routine/average risk or positive family history) to 75 years of age and after 75 years of age, assessed every 2 years.

Main Outcomes And Measures: Incidence of CRC and CRC-related mortality confirmed by National Death Index, medical records, and pathology reports.

Results: Among 56 374 participants who reached 75 years of age during follow-up (36.8% men and 63.2% women), 661 incident CRC cases and 323 CRC-related deaths were documented. Screening endoscopy after 75 years of age was associated with reduced risk of CRC incidence (multivariable hazard ratio [HR], 0.61; 95% CI, 0.51-0.74) and CRC-related mortality (HR, 0.60; 95% CI, 0.46-0.78), regardless of screening history. The HR comparing screening with nonscreening after 75 years of age was 0.67 (95% CI, 0.50-0.89) for CRC incidence and 0.58 (95% CI, 0.38-0.87) for CRC-related mortality among participants who underwent screening endoscopy before 75 years of age, and 0.51 (95% CI, 0.37-0.70) for CRC incidence and 0.63 (95% CI, 0.43-0.93) for CRC-related mortality among participants without a screening history. However, screening endoscopy after 75 years of age was not associated with risk reduction in CRC death among participants with cardiovascular disease (HR, 1.18; 95% CI, 0.59-2.35) or significant comorbidities (HR, 1.17; 95% CI, 0.57-2.43).

Conclusions And Relevance: In this cohort study, endoscopy among individuals older than 75 years was associated with lower risk of CRC incidence and CRC-related mortality. These data support continuation of screening after 75 years of age among individuals without significant comorbidities.
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http://dx.doi.org/10.1001/jamaoncol.2021.1364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138747PMC
July 2021
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