A diet high in fiber and yogurt is associated with a reduced risk for lung cancer

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 diet high in fiber and yogurt is associated with a reduced risk for lung cancer, according to a study by Vanderbilt University Medical Center researchers published in JAMA Oncology.

The benefits of a diet high in fiber and yogurt have already been established for cardiovascular disease and gastrointestinal cancer.

The new findings based on an analysis of data from studies involving 1.4 million adults in the United States, Europe and Asia suggest this diet may also protect against lung cancer.

Participants were divided into five groups, according to the amount of fiber and yogurt they consumed.

Those with the highest yogurt and fiber consumption had a 33% reduced lung cancer risk as compared to the group who did not consume yogurt and consumed the least amount of fiber.

“Our study provides strong evidence supporting the U.S. 2015-2020 Dietary Guideline recommending a high fiber and yogurt diet,” said senior author Xiao-Ou Shu, MD, Ph.D., MPH, Ingram Professor of Cancer Research, associate director for Global Health and co-leader of the Cancer Epidemiology Research Program at Vanderbilt-Ingram Cancer Center.

“This inverse association was robust, consistently seen across current, past and never smokers, as well as men, women and individuals with different backgrounds,” she added.

Shu said the health benefits may be rooted in their prebiotic (nondigestible food that promotes growth of beneficial microorganisms in the intestines) and probiotic properties.

The properties may independently or synergistically modulate gut microbiota in a beneficial way.

The study’s lead authors are Jae Jeong Yang, Ph.D., a visiting research fellow from the Seoul National University, South Korea, and Danxia Yu, Ph.D., assistant professor of Medicine at Vanderbilt.


The beneficial health effects of consuming healthy dietary patterns rich in dietary fiber from whole plant foods include: improving gut health; lowering elevated LDL-cholesterol; reducing the risk of excessive weight gain and obesity; decreasing cardiovascular disease (CVD), coronary heart disease (CHD) and mortality risks; reducing risks of several cancers, stroke and type 2 diabetes; and improving the odds for successful aging [1,2,3,4,5].

Whole fruits (e.g., fresh, frozen, canned or dried) are recognized for their fiber content, very low to moderate energy density, and as being important sources of healthy nutrients (e.g., potassium and vitamin C) and phytochemicals (e.g., polyphenols and carotenoids), which work synergistically to support a wide range of health benefits [1,2,6,7,8,9]. Although most of the fiber from whole fruit is removed during fruit juice processing, 100% fruit juices retain similar levels of other healthy vitamins, minerals and phytochemicals [10].

About 90% of the US (and other Western) populations do not eat the recommended daily intake of fruit (e.g., 1 to 1 ½ cups for children 2–8 years, 1 ½ cups for adolescent girls and boys, 1 ½ to 2 cups for women, and 2 cups for men) [11].

The typical daily fruit intake is about half the recommended level with juice consumption making up one-third of this level for adults and one-half for children [11].

Consequently, fruit fiber is a relatively small component of the total fiber consumed in populations eating a Western dietary pattern.

The 2015–2020 Dietary Guidelines for Americans named fiber as a major shortfall nutrient of important public health concern [1,12].

Fiber is defined as carbohydrates from plant cell walls, resistant starch and oligosaccharides that are resistant to gastric acidity, hydrolysis by mammalian enzymes, and absorption in the upper gastrointestinal tract.

The human gastrointestinal tract, and cardiometabolic and immune systems evolved on high fiber plant-based diets (≥50 g total fiber/day), including the consumption of wild berries and other native fiber-rich edible plants by hunter-gathers, and later grains, fruits and vegetables from traditional farming, which provided fiber rich diets until the mass globalization of Western dietary patterns in the 20th and 21st centuries.

The low fiber Western diet has contributed to increased risk of weight gain, inflammation, chronic diseases and other health concerns in large part by increasing the risk of colonic microbiota dysbiosis associated with unhealthy immunity, cardiometabolic and energy regulatory processes [13,14,15,16,17].

With the current high prevalence of the Western diet, only about 3% of men and 6% of women habitually consume ≥14 g fiber/1000 kcal, the threshold level considered adequate for optimal health [18,19,20,21,22,23,24].

In most Western countries, the typical fiber intake is about half the adequate level. Specific adequate total daily fiber intake varying by age and gender is summarized in Figure 1 [18].

Fiber-rich, plant-based dietary patterns are a major contributor to prebiotic health effects, which stimulate the growth of beneficial intestinal bacterial species to promote and maintain a healthy colonic microbiota ecosystem (microbiome) in large part from fermentation of fiber to short chain fatty acids (SCFAs) [1,2,3,4,9,14,15,16,17,22,23,24,25,26,27,28,29,30,31,32,33,34,35].

The primary aim of this narrative review article is to examine emerging prebiotic and other health effects associated the intake of whole fruits, especially fruit fiber, throughout the human lifecycle.

Fruit as a Prebiotic Source

2.1. Fruit Fiber Components and Fermentability

A comprehensive table of whole fruit total fiber and sub-components, sugar, and energy content per serving is provided in Table 1. As fruit ripens after harvest, the 3-dimensional hydrated cell wall fiber components pectin, hemicellulose and cellulose become increasingly disassembled, allowing for more microbial access and enhancing susceptibility to fermentation [26,27,28,36,37].

The process of eating, and then digestion in the upper gastrointestinal tract further breaks down the whole fruit into smaller particles and damages the fruit cell wall surfaces to enable greater colonic bacterial enzymatic breakdown and fermentation. Starchy fruits (e.g., bananas and plantains) provide fiber from both cell walls and resistant starch stored within the cells [32,38].

Generally, it has been assumed that soluble fibers are fermented more rapidly and completely compared with insoluble fibers, but this view is changing, especially concerning ripe fresh fruits, with cell wall “insoluble fibers” in a hybrid hydrated and partially disassembled state with increased susceptibility to fermentation [22,26].

Also, it is hard to rely on insoluble and soluble quantifications as current standardized methods have many limitations in accurately separating them into individual fractions. Whole fruit can provide a major source of fermentable fiber to support colon prebiotic activity, which can contribute to a wide range of potential human health benefits with sustained consumption at recommended levels.

 Pectin

The most extensively studied fruit fiber prebiotic component is pectin, which comprises on average 35% of fruit fiber cell wall content [9,37].

A Korean in vitro human colonic microbiota model system study (3 male donors with diverse microbiota profiles) confirmed the effectiveness of pectin in promoting robust prebiotic activity in all subjects [39].

Although donors had differences in baseline colonic microbiota composition, there were similar increases in healthy bacteria after pectin fermentation including species belonging to butyrate producing Clostridium cluster XIV (e.g., Lachnospira), and Sutterella. After pectin intake, microbiota production of SCFAs, acetate and butyrate levels increased 6 h post intake. Acetate continuously increased up to 18 h, then rapidly decreased by 36 h. Butyrate steadily increased approximately 28% by 48 h. Propionate slowly increased after 12 h until about 48 h at a much slower rate than acetate or butyrate.

Increased butyrate levels are used as the main energy source by colonocytes to maintain the colonic protective barrier and in lowering colonic luminal pH to inhibit pathogenic bacteria. A comparison between apple pectin and inulin using a human colonic microbial anaerobic continuous-flow fermenter found that they were both effective in promoting prebiotic activity with anti-inflammatory effects, although apple pectin was three times more effective in promoting Bacteroides and overall microflora diversity than inulin, presumably reflecting the differing complexity of the two prebiotics [40].

A recent study using an in vitro Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) suggests that citrus pectin stimulated the production of butyric acid in the simulated transverse and descending colon, as well as the growth of genera LactobacillusMegamonas, and Lachnospiracea with related anti-inflammatory effects, and a reduction of ammonium ions [41].

A 2018 in vitro study also suggests that pectins have the potential to improve the survival of probiotic bacteria such as Lactobacillus in the stomach and small intestine [42]. Overall, these studies find that fruit fiber, especially pectin, can help re-balance the colonic microbiota towards a higher anti-inflammatory profile by: (1) increasing the Bacteroidetes/Firmicutes ratio, and increasing the abundance of Bifidobacterium and Clostridium cluster XIV, resulting in enhanced colonic mucosal barrier integrity and function, increased mucosal immunity, increased butyrate production, and a decrease in enteric pathogens; (2) promoting Eubacterium eligens, which upregulates pectinolytic enzymes; and (3) supporting certain Faecalibacterium prausnitzii strains in utilizing the fermentation of pectin to exert anti-inflammatory effects [31,32,33,43,44,45,46,47,48]. Pectin is a major fruit prebiotic that has been extensively studied and shown to promote a healthy, anti-inflammatory colonic microbiota ecosystem with greater microflora diversity than inulin.

Fruits

Several in vitro human fecal microbiota model fermentation systems studies support the prebiotic effects of whole fruits. A study which evaluated apples with an in vitro batch culture colonic model system (pH 5.5–6.0; 37 °C; inoculated with feces from three healthy donors; 3 varieties) found that all the apple varieties exhibited beneficial prebiotic activity by improving colonic microbiota bacterial diversity, and increasing Actinobacteria relative abundance and total SCFAs levels (p < 0.05) [49].

The Renetta Canada apple variety, rich in fiber and polyphenols in particular had positive consequences for human health by increasing BifidobacteriaF. prausnitzii, butyrate levels and polyphenol microbial metabolites (p < 0.05).

Raisins assessed with a simulated in vitro digestive system with dynamic mastication, gastric, duodenal and colonic human models showed that raisins significantly increased the proportion of Bifidobacteria and Lactobacilli, decreased numbers of Firmicutes, and approximately doubled the fecal concentration of propionate and butyrate compared to controls [50]. Commonly consumed whole fruits can promote a healthy microbiota ecosystem by the actions of their fiber and polyphenolics.

 Cancer

Excess body weight, sedentary lifestyles, unhealthy dietary habits such as low fiber, fruits and vegetables and high meat intake can increase cancer risk [256]. The American Cancer Society recommends eating >2.5 cups/day of fruits and vegetables for cancer prevention [257].

3.6.1. Colorectal Cancer

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world and a leading cause of cancer death, despite major advances in screening, surgery and oncology. The 2007 and 2011 World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) reports showed convincing meta-analyses evidence that fiber, fruit and vegetables are inversely associated with CRC risk [258,259]. A 2011 meta-analysis (19 cohort studies; 1.7 million subjects) found an inverse association between intake of fruits and vegetables and CRC risk with most of the risk reduction observed at about 100 g/d (Figure 18) [260]. An EPIC prospective cohort study (>500,000 participants) observed that the risk of CRC was inversely associated with intakes of total fruits and vegetables, and total fiber [261]. The Shanghai Men’s Health Study (61,274 men) observed that increased fruit intake was significantly inversely associated with CRC risk, whereas vegetable intake was not associated with CRC risk [262].

A systematic review and meta-analysis observed a lower risk of CRC for whole grains by 5% per 30 g/d, fruits and vegetables by 3% per 100 g/d, dairy by 7% per 200 g/d and an increased CRC risk for red meat by 12% per 100 g/d and for processed meat by 17% per 50 g/d [263]. A meta-analysis (2 cohort and 5 case-control studies) estimated that higher apple intake reduced CRC risk by 28% (p = 0.001) [264].

The Malmö Diet and Cancer Study (27,931 participants) observed high intakes of total fiber, and fruits and berries significantly lowered risk for colon cancer by approximately 30% compared to no lowering effects for vegetables and fiber rich cereals [265], which is consistent with a 2018 systematic review and meta-analysis (25 observational studies) observation that higher total fiber intake reduced colon cancer risk by 26% (p = 0.000) [266].

A meta-analysis of 20 observational studies [267] and another meta-analysis of 5 cohort and 17 case-control studies [268] showed that each 10-g fruit fiber and high fruit intake reduced adenoma risk by 21% compared to a reduced risk of 9% for vegetables. Secondary analyses of the Polyp Prevention Trial found that super dietary compliers consuming 12 g fiber and 3 fruit and vegetable servings/1000 kcals significantly reduced adenoma recurrence risk by 32% and lowered multiple and/or advanced adenoma recurrence risk by 50% compared to less compliant controls (p < 0.05) after 4 years [269]. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (57,774 subjects; 12 years of follow-up) found that higher fruit and vegetable intake significantly reduced the risk of multiple adenomas by 39% and risk of CRC in individuals with high processed meat intakes by 26% [270].

Pooled data from the Nurses’ Health Study and Health Professionals Follow-up Study (1575 participants) observed lower multivariate adjusted CRC specific mortality risk per 5-g increment for fruit fiber by 9% lower risk (p = 0.58), vegetable fiber by 18% (p = 0.22), and cereal fiber by 33% (p = 0.007) [271]. Fiber is the primary dietary component of whole plant foods associated with promoting a healthy colonic microbiota which aids in reducing tumorigenic inflammation, carcinogen production, and altered cellular responses in susceptible individuals [272].

Lung Cancer

Lung cancer is the leading cause of cancer death worldwide with approximately 2 million global deaths attributed to cigarette smoking [273]. Tobacco use is the leading cause of lung cancer resulting in 55% of lung cancer deaths in women and over 70% of lung cancer deaths in men.

The current evidence from prospective studies suggest a potential protective role for fruit in lung cancer etiology. A 2015 dose-response meta-analysis of cohort studies (19 studies; approx. 2 million participants) found that each one serving of fruits reduced lung cancer risk by 5% compared to a 3% reduction for each serving of vegetables [274].

Another 2015 meta-analysis of fruit (38 observational studies; 20,213 lung cancer cases) showed that increased fruit intake lowered lung cancer risk by 20% compared to lower fruit intake [275]. The associations with fruit and lower lung cancer risk were stronger for women than for men. A 2016 systematic review and meta-analysis (18 prospective studies) found that high fruit intake reduced lung cancer risk by 18% with each 100-g intake lowering risk by 8% up to 400-g/day [276].

These risk reductions were significant in current smokers but not in former or never smokers. A 2014 EPIC prospective cohort study (>500,000 participants; 10 European countries) observed that the risk of lung cancer was inversely associated with fruit intake but was not associated with vegetable intake; this association with fruit intake was restricted to smokers [261].

In a 2016 meta-analysis (3 case-controlled and 7 cohort studies) the high intake of apples was found to significantly lower lung cancer risk by 25% in case-control studies (p = 0.001) and 11% in cohort studies (p < 0.001) compared to low intake [264]. The Black Women’s Health Study (47,000 women) observed an insignificant 14% lower lung cancer risk for high vs. low fruit and vegetable intake, regardless of smoking history, but the overall fruit and vegetable intake was relatively low in this study population [277].

Successful Aging

Successful aging is associated with being free of excessive progressive deterioration of physical and mental functions and chronic disease (obesity, coronary artery disease, stroke, diabetes, and cancer); having good mental, physical and respiratory health, and functional independence [278].

Health issues such as increased prevalence of chronic disease and risk of premature death increase substantially beginning in middle-age, but an estimated 80% of health problems in older age could be prevented or delayed by healthy lifestyle changes. A French cohort study (2796 middle aged; 13 years) observed that a higher adherence to: (1) a Western dietary pattern reduced the odds for successful aging by 17%; (2) a healthy high energy dietary pattern improved odds for successful aging by 7%; and (3) a healthy moderate energy dietary pattern improved odds for successful aging by 46% (Figure 19) [279].

Mechanisms

Aging is a complex process at the cellular level involving genetic changes that cause a progressive loss of physical capabilities [290]. Many of the factors that control aging are related to gene expression including epigenetic and telomeric changes that are outside of the information encoded in the DNA. Lifestyle factors such as diet, exercise, and stress can modify cell function and change epigenetic and telomere information that affect gene expression and nucleic stability.

Long telomeres in old age help to maintain key cellular processes that reduce the number of years a person experiences poor health during aging. A 2018 NHANES analysis (5674 adults) found that fiber intake of 10 g per 1000 kcal increased leukocyte telomere length by 67 base pairs (p = 0.01), which reduced biologic (cellular) aging by 4.3 years compared to the low fiber Western diets of 6.6 g fiber per 1000 kcal [291]. Two longitudinal studies (521 subjects; 5 years) found that longer telomere length was significantly predictive of lower body weight, BMI, waist circumference, and dietary inflammatory index, and was associated with the higher fruit and fiber intake associated with high adherence to the Mediterranean diet [292,293].

The Framingham Heart Study Offspring cohort study observed that the intake of whole fruit up-regulated epigenetic gene function for immunosurveillance, and chromosome and telomere maintenance pathways, attributed to the effects of fruit fiber on colonic microbiota health [294].

Emerging fiber mechanisms associated with successful aging include:

(1) enhancing the colonic probiotic microflora profile and production of SCFAs;

(2) improving the colonic barrier function to protect against clinical inflammation;

(3) increasing colonic peptides that are important in glucose and insulin homeostasis and lipid metabolism; and

(4) mimicking many of the effects of caloric restriction including upregulation of genes involved in energy metabolism [295].

Lung Function

Impaired lung function related to allergies, asthma, environmental factors and tobacco usage is a major worldwide health issue affecting 100 s of millions of children and adults.

Asthma Severity and Wheezing

Asthma, a chronic respiratory inflammatory condition, represents a major public health burden worldwide. It affects about 300 million people of all ages and is increasing in prevalence [296,297].

Symptoms of asthma in low- and middle-income countries can be as high as rates found in more developed countries. Among children aged 5–14 years, asthma is among the top ten global ranking conditions for disability-adjusted life years. Growing evidence from observational studies indicates that increased whole fruit intake is associated with reduced severity of asthma symptoms such as airway constriction, inflammation, bronchial hyper-responsiveness, coughing, wheezing, and chest tightness.

A 2017 meta-analysis of fruit and vegetable intake on risk of asthma/wheeze and immune responses (30 cross-sectional, 13 cohort, 8 case-control and 7 experimental studies; children and adults) found no significant association between fruit intake and risk of prevalence of asthma but the intake of fruit was inversely associated with the severity of asthma in secondary prevention studies, with a higher fruit intake lowering severity by 39% [297].

Fruit intake was also negatively associated with risk of wheezing. Vegetable intake was not associated with the severity of asthma or wheezing. A systematic review by the European Academy of Allergy and Clinical Immunology recommended an increased intake of fresh fruits as a way of reducing the number and severity of asthma flare-ups, particularly in children [298].

The Prevention and Incidence of Asthma and Mite Allergy study (2870 children; followed from birth to 8 years of age) observed that each day of fresh fruit consumption per week at 2–3 years of age was associated with reduced asthma symptoms and atopy by 7% at age 8 years, but no asthma protection was observed for cooked vegetables [299].

Long-term fruit intake was inversely associated with asthma symptoms and sensitization to inhaled allergens with 10% reduction for each daily serving. A Brazilian case-controlled study (171 children; 30 days) observed that regular consumption of fruits was associated with an 81% lower risk of asthma severity or persistence [300].

A Portuguese cross-sectional study (174 asthmatics) observed that higher fresh fruit intake significantly decreased risk of uncontrolled asthma by 71% (p = 0.015) [301].

lso, high adherence to the Mediterranean diet reduced the risk of uncontrolled asthma by 78%, after adjusting for gender, age, education, inhaled corticosteroids and energy intake (p-trend = 0.028). In children, a 2014 systematic review and meta-analysis (1 cohort study and 13 cross-sectional studies) found higher fruit intake significantly reduced wheezing in children ≤11 years old by 17%, and for children >11 years old by 19% and reduced asthma severity in children >11 years old by 24%, but not for children ≤11 years old who showed an insignificant reduced risk of 11% [302].

In adults, a meta-analysis (3 cohorts, 2 case-controls, and 4 cross-sectional studies) found that higher intake of fruit reduced the overall risk of asthma severity by 23% compared with the lowest intake. In subgroup analysis, increased intake of apples or citrus fruit reduced the risk of asthma severity by about 24%. A 2016 RCT (90 adults with uncontrolled asthma; fruit and vegetable rich DASH diet vs. usual-care control; 6 months) found that the DASH diet modestly but significantly improved overall asthma control score by 19% (p = 0.04) and quality of life score by 39% (p = 0.004) compared to the subjects’ usual diet [303].

The 2017 (Latin American) International Study of Asthma and Allergies in Childhood Phase III (143,967 children with asthma; 11 Latin American countries) observed in children 6 to 7 years of age that adequate fruit intake can reduce wheezing risk by up to 35% compared to low fruit intake [304].

For 13 to 14-year-old children, there were similar but slightly attenuated wheezing lowering effects for increased fruit intake. A 2018 meta-analysis showed that higher fruit intake was associated with increased colonic microbiota SCFAs levels which suppressed asthma airway restrictions by helping to lower levels of CRP, TNF-α, and mast cell, and increasing γ δ-T cell and Treg cell numbers and function (p < 0.05) [305]. Low fruit (e.g., fiber and polyphenols) can increase microbiota dysbiosis, which is associated with increased risk of asthma severity [303,304,305]. I

ndividuals with severe persistent asthma often have a high adherence to the Western diet and consume significantly less fruit fiber compared to healthy controls, which is partly associated with the increased colonic microbiota dysbiosis and lung axis effects associated with increased airway inflammation and adverse immune response reducing breathing capacity of the lungs [306,307,308].

A meta-analysis (2 RCTs; 249 children; age range 2–5 years) found that prebiotic fiber reduced the risk of asthma or wheezing by 63% when compared to the control group [309]. Adequate intake of whole fruits is associated with reduced severity of asthma in children and adults through fruit fiber effects linked to a healthier colonic microbiome that actively suppresses the severity of airway inflammatory restrictions.

Chronic Obstructive Pulmonary Disease (COPD)

The estimated global number of cases of COPD is approximately 400 million [310]. COPD is multifactorial, and the risk factors include genetic and environmental quality factors (e.g., tobacco smoke, occupational inhalants and air pollutants originating from biomass burning and traffic exhaust) [310,311].

Although tobacco smoking is an established risk factor for COPD, up to 50% of cases of COPD can be attributed to nonsmoking risk factors. Observational studies suggest that fruit intake is positively associated with lung function and inversely related to COPD respiratory symptoms and death and more effective than increased vegetable and whole-grain intake [312].

A cross-sectional analysis of the Atherosclerosis Risk in Communities Study (15,792 adults) observed that high adherence to a prudent diet rich in fruits and vegetables was associated with a lower prevalence of COPD by 18%, coughing by 23%, and a higher forced expiratory volume compared to 62% increased prevalence of COPD, a higher level of wheezing, coughing and phlegm by 27 to 37% and a reduced forced expiratory volume for high adherence to the Western diet [313].

A 2017 Cohort of Swedish Men study (44,335 men; 13.2 years) observed a strong inverse association for total fruit and vegetable intake and COPD in smokers but not in never smokers (p-interaction = 0.02) [314].

The risk of COPD was significantly reduced in current smokers by 8% and in ex-smokers by 4% for each one serving/day of total fruit and/or vegetables. A Swedish Mammography Cohort (34,739 women; age range 48–83 years; 12-year follow-up) observed that women consuming 2.5 or more fruit servings/day had a 37% lower risk of COPD (p-trend < 0.0001) compared to those consuming <0.8 serving/day [315].

Long-term vegetable intake was not associated with lower COPD risk. In current and ex-smokers, women with low fruit intake (<1 serving/day) had a 38-fold and 13-fold higher COPD risk, respectively, than those consuming 3 or more fruit servings/day. A 2016 NHANES analysis (1921 adults) observed that participants with higher fiber intake had healthier mean forced expiratory volume by 82 mL/s and forced vital capacity by 129 mL/s, than those with lower fiber intake (p = 0.05 and 0.01), which is consistent with the consumption of higher vs. lower fruit intake [316].

The 2018 Cohort of Swedish Men study (45,058 men w; 13.1 years) observed an inverse association between total fiber intake (≥ 37 g/day vs. <24 g/day) and COPD in smokers by 46% and ex-smokers by 38% [317]. Never smokers had a 7% reduction in COPD with higher fiber intake (p interaction = 0.04). Fruit fiber reduced COPD risk in smokers by 35% (p-trend = 0.001) and in ex-smokers by 23% (p-trend = 0.17). The development or progression of COPD is associated with an over-active immune system characterized by increased neutrophil and macrophage activation [318].

Adequate fruit fiber intake promotes healthy lung immune function via the colonic microbiota-liver-lung axis, which affects systemic inflammatory cytokines and immune mediators (notably, IL-6 and CRP).


More information: Jae Jeong Yang et al, Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk, JAMA Oncology (2019). DOI: 10.1001/jamaoncol.2019.4107

Journal information: JAMA Oncology
Provided by Vanderbilt University Medical Center

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