Abstract
Several case-control studies have reported that mushroom consumption may be associated with reduced risk of certain cancers. However, epidemiologic studies have not yet prospectively examined the association of mushroom consumption with total and various site-specific cancer risk. This prospective cohort study included 68,327 women (Nurses’ Health Study, 1986–2012) and 44,664 men (Health Professionals Follow-up Study, 1986–2012) who were free of cancer at baseline. Mushroom consumption was assessed at baseline using a validated food frequency questionnaire. Covariates were assessed using biennial questionnaires during the follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of total and 17 site-specific cancers associated with mushroom consumption. During up to 26 years of follow up, we documented 22,469 incident cancer cases (15,103 in women and 7,366 in men). In the pooled multivariable analysis, participants who consumed 5 or more servings of mushrooms per week had no significantly different risk of total cancer (HR=1.06, 95% CI=0.98–1.14) than participants who almost never consumed mushrooms. We consistently found no association between mushroom consumption and risk of 16 site-specific cancers. However, there was a marginal positive association between mushroom consumption and risk of lung cancer (P-trend=0.05). In conclusion, we found no association between mushroom consumption and total and site-specific cancers in US women and men. More prospective cohort studies are needed to examine the associations for specific cancer types in diverse racial/ethnic groups.
Keywords: Mushroom, diet, nutrition, cancer, cohort study
Introduction
Cancer is among the leading causes of death in both developed and developing countries and was responsible for an estimated 9.6 million deaths in 2018.(1) Moreover, cancer incidence and mortality rates are consistently increasing worldwide, posing an enormous global burden.(2) Thus, cancer prevention has been a major target of research in public health. Studies have found that many cancers are attributable to preventable factors such as diet.(3) The World Cancer Research Fund/American Institute of Cancer Research has reported that certain dietary factors or patterns have ‘convincing’ or ‘probable’ evidence to increase or decrease several types of cancers.(4)
Mushrooms are generally known as a healthy food and are widely consumed in many countries. Mushrooms contain many important nutrients including riboflavin, niacin, vitamin D, fiber, selenium, potassium, and bioactive compounds.(5) Laboratory studies have shown some evidence that mushrooms and mushroom extracts have anticarcinogenic and immunomodulating properties.(6,7) However, human studies evaluating the relation between mushroom intake and cancer risk are scarce. Several retrospective case-control studies have reported that high mushroom consumption may be associated with lower risk of breast cancer.(8) Yet, retrospective case-control studies are prone to selection and recall biases, which are particularly problematic when addressing dietary exposures, and thus the observed association may have been overestimated. To date, only a few prospective cohort studies have examined the association of mushrooms, as a part of multiple food items, with certain cancer sites. Moreover, the existing evidence is largely from relatively small studies from Asian countries. More prospective studies are warranted in diverse population to better understand a role of mushroom consumption in the development of cancers. Therefore, we prospectively examined the association between mushroom consumption and risk of total and site-specific cancer in two large US prospective cohorts of women and men.
Materials and Methods
Study population
The Nurses’ Health Study (NHS) is an ongoing prospective cohort study which included 121,700 US female nurses aged 30 to 55 years in 1976. The Health Professionals Follow-up Study (HPFS) is a parallel cohort study which included 51,529 US male health professionals aged 40 to 75 years in 1986. Participants were asked to complete a mailed questionnaire at enrollment and every two years thereafter to assess information on demographics, lifestyle factors and medical history. Dietary data were assessed every four years using food frequency questionnaires (FFQ). The follow-up rates of two cohorts exceeded 90%.
In this study, we included participants who completed a FFQ in 1986. We excluded participants previously diagnosed with cancer (except for melanoma skin cancer) or had implausible calorie intake (<500 or ≥3500 for women; <800 or ≥4200 for men) at baseline. The final sample included 68,327 women and 44,664 men. This study was conducted in accordance with recognized ethical guidelines and approved by the Institutional Review Boards of the Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health. Informed written consent was obtained from all individual participants.
Mushroom consumption and covariate assessment
In 1986, participants reported how often on average they consumed mushrooms (fresh, cooked or canned) during the past year among the following nine choices: never or less than once a month, 1–3 times a month, once a week, 2–4 times a week, 5–6 times a week, once a day, 2–3 times a day, 4–6 times a day, or more than 6 times a day. Other dietary data were collected as well using the same FFQs. The validity and reproducibility of FFQs have been described previously.(9–12) Briefly, in a validation study, the de-attenuated correlation comparing mushroom intake recorded in multiple prospectively collected diet records to mushroom intake reported in the FFQ was 0.65 and the average de-attenuated correlation for all food items was 0.57 in men and 0.52 in women.(11,12). We characterized participants’ diet into two major patterns defined as Prudent and Western dietary patterns based on approximately 39 predefined food groups (excluding mushrooms) from FFQs via a principal component analysis.(13) Other covariates including lifestyle and medical history were collected using biennial questionnaires over the follow-up.
Outcome assessment
Participants self-reported diagnoses of cancer and other diseases from biennial questionnaires. For participants who reported a cancer diagnosis, we obtained permission to acquire their medical records and pathologic reports. Study physicians, blinded to exposure status, reviewed medical records to confirm the cancer diagnosis and abstracted the information on histology, stage and anatomical location of the cancer. Confirmed cancers were defined according to the International Classification of Diseases, 9th revision. Deaths were identified through searching the National Death Index and reports from next-of-kin and postal authorities.
Statistical analysis
Person-years of the follow-up were accrued from the date of return of the 1986 baseline questionnaire to the date of diagnosis of cancer (excluding melanoma skin cancer), death or the end of follow-up (June 2012 for the NHS; January 2012 for the HPFS), whichever came first. Mushroom consumption at baseline was categorized into 5 categories as follows: (1) Never or less than once per month (almost never), (2) Less than once a week, (3) Once a week, (4) 2–4 times a week, (5) 5+ times a week. We also used mushroom consumption as a continuous variable (i.e., per 2 servings/week increase).
Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) of total and site-specific cancer associated with mushroom consumption. Age and calendar time were used as stratification variables. Multivariable models adjusted for race (white or non-white), height (continuous), body mass index (quintiles), family history of cancer (yes or no), physical exam in past two years (yes or no), history of colonoscopy or sigmoidoscopy (yes or no), smoking in pack years (never smoker, 1–4.9, 5–19.9, 20–39.9, or ≥40), physical activity (quintiles), regular aspirin use (≥2 times/week; yes or no), multivitamin use (yes or no), total energy intake (quintiles), alcohol consumption (0, 0.1–4.9, 5.0–14.9, 15.0–29.9, or ≥30 g/d), red and processed meat intake (quintiles), Prudent dietary pattern (quintiles) and Western dietary pattern (quintiles). We additionally adjusted for prostate specific antigen test in past two years (yes or no) for men and menopausal status (pre-menopause or post-menopause), postmenopausal hormone use (never, past, or current), and mammogram in past two years (yes or no) for women. All covariates were updated over the follow-up period. We tested for a linear trend of mushroom consumption by including mushroom consumption as a continuous variable in the models. Proportional hazards assumption was tested by including a cross-product term of mushroom consumption and time variable in the models (P>0.05). Since we did not observe significant heterogeneity by sex, we pooled the data of women and men for cancers that are not sex-specific (i.e., postmenopausal, endometrial, ovarian cancers for women and advanced prostate cancer for men). Lastly, we conducted stratified analysis by smoking status to examine whether the association between mushroom consumption and risk of cancer differ by smoking status.
We used the SAS software (version 9.4, SAS Institute) for all analyses. All statistical tests were 2-sided and P<0.05 was considered statistically significant. Multiple comparison was adjusted using Bonferroni-corrected P<2.8×10−3 (0.05 divided by 18 cancer outcomes).(14)
Results
Participants who consumed more mushrooms had higher physical activity, multivitamin use, alcohol use, and overall diet quality (i.e., high Prudent and low Western dietary patterns) (Table 1). They also tended to have more frequent physical examinations, cancer screenings (i.e., physical examination, colonoscopy, sigmoidoscopy or mammogram) and were less likely to be never smokers. The number of pack years was lower among ever smokers who ate more mushrooms.
Table 1.
Age standardized baseline characteristics of participants according to mushroom consumption in 1986
| Frequency of mushroom consumption, per serving |
|||||
|---|---|---|---|---|---|
| Characteristic | Never or Almost never | <1/week | 1/week | 2–4/week | 5+/week |
| Women (NHS) | |||||
| No of person | 15318 | 22614 | 18376 | 9100 | 2919 |
| Age (years) | 53.4 (7.2) | 53.0 (7.2) | 52.5 (7.1) | 52.9 (7.0) | 52.9 (6.8) |
| White (%) | 97.2 | 97.7 | 98.3 | 98.0 | 98.1 |
| Family history of cancer (%) | 15.8 | 16.3 | 16.5 | 16.8 | 16.4 |
| Height (cm) | 163.6 (6.1) | 163.8 (6.2) | 163.9 (6.2) | 164.0 (6.2) | 164.4 (6.2) |
| Body mass index | 25.3 (4.8) | 25.2 (4.8) | 25.4 (4.8) | 25.5 (4.8) | 25.3 (4.7) |
| Post-menopause (%) | 54.9 | 54.2 | 54.9 | 54.2 | 54.1 |
| Current hormone therapy use (%) | 13.3 | 14.3 | 15.1 | 16.0 | 16.6 |
| Physical examination in past 2 years (%) | 64.8 | 66.2 | 67.1 | 68.5 | 69.5 |
| History of colonoscopy or sigmoidoscopy (%) | 16.8 | 17.8 | 18.7 | 18.7 | 20.5 |
| Mammogram in past 2 years (%)a | 71.8 | 75.7 | 77.2 | 78.6 | 80.5 |
| Regular aspirin use (%) | 40.1 | 40.0 | 42.0 | 41.9 | 40.4 |
| Current use of multivitamin (%) | 39.7 | 42.2 | 43.0 | 44.8 | 45.8 |
| Physical activity (MET h/week) | 11.9 (19.1) | 12.8 (18.6) | 15.1 (21.6) | 16.6 (21.2) | 19.8 (25.9) |
| Never smoker (%) | 49.4 | 45.0 | 41.1 | 40.6 | 37.4 |
| No of pack years among ever smokers | 24.3 (19.1) | 23.0 (19.1) | 22.8 (18.9) | 22.1 (18.8) | 21.1 (18.2) |
| Calorie intake (kcal/day) | 1553 (505) | 1536 (488) | 1567 (483) | 1602 (483) | 1625 (501) |
| Alcohol intake (g/day) | 4.2 (8.3) | 6.0 (9.5) | 7.4 (10.3) | 8.1 (10.6) | 9.6 (11.8) |
| Red and processed meat (no of servings/week) | 7.0 (3.6) | 6.8 (3.4) | 6.9 (3.4) | 6.9 (3.5) | 6.5 (3.8) |
| Prudent pattern (highest quintile), % | 9.2 | 13.2 | 23.0 | 39.2 | 51.4 |
| Western pattern (highest quintile), % | 22.3 | 19.1 | 19.8 | 19.5 | 17.5 |
| Men (HPFS) | |||||
| No of person | 9962 | 16106 | 11708 | 5763 | 1125 |
| Age (years) | 55.8 (10.0) | 54.1 (9.8) | 53.1 (9.5) | 53.9 (9.7) | 53.7 (9.5) |
| White (%) | 89.5 | 89.8 | 90.7 | 90.5 | 89.5 |
| Family history of cancer (%) | 8.3 | 8.2 | 8.6 | 9.2 | 7.3 |
| Height (cm) | 178.1 (7.0) | 178.1 (7.0) | 178.1 (7.2) | 178.1 (7.6) | 178.7 (6.7) |
| Body mass index | 25.4 (3.3) | 25.5 (3.4) | 25.6 (3.2) | 25.7 (3.6) | 25.8 (3.9) |
| Physical examination in past 2 years (%)a | 56.9 | 58.8 | 60.8 | 59.3 | 62.8 |
| History of colonoscopy or sigmoidoscopy (%) | 24.0 | 25.9 | 26.7 | 27.9 | 28.5 |
| Prostate specific antigen test in past 2 years (%)a | 35.1 | 37.8 | 37.6 | 38.2 | 39.4 |
| Regular aspirin use (%) | 29.4 | 29.4 | 28.7 | 29.4 | 32.3 |
| Current use of multivitamin (%) | 40.5 | 41.2 | 41.8 | 43.5 | 44.6 |
| Physical activity (MET h/week) | 18.7 (26.4) | 20.0 (27.8) | 22.0 (31.8) | 23.7 (30.2) | 29.0 (42.0) |
| Never smoker (%) | 49.0 | 43.7 | 43.8 | 43.4 | 40.8 |
| No of pack years among ever smokers | 26.3 (19.8) | 25.4 (19.5) | 25.0 (18.9) | 25.0 (19.3) | 23.1 (14.1) |
| Calorie intake (kcal/day) | 1906 (625) | 1921 (594) | 2036 (600) | 2157 (635) | 2298 (629) |
| Alcohol intake (g/day) | 8.5 (14.2) | 11.1 (15.1) | 12.6 (15.8) | 13.5 (16.2) | 15.0 (18.0) |
| Red and processed meat (no of servings/week) | 7.1 (5.4) | 6.8 (5.0) | 6.8 (4.9) | 6.6 (5.2) | 6.1 (5.2) |
| Prudent pattern (highest quintile), % | 11.3 | 12.6 | 21.4 | 43.3 | 65.6 |
| Western pattern (highest quintile), % | 20.7 | 19.0 | 19.9 | 21.5 | 21.0 |
Abbreviation: HPFS, health professionals follow-up study; MET, metabolic equivalent task; NHS, nurses’ health study.
Values are means (SD) or percentages and are standardized to the age distribution of the study population (except for age).
Data from 1988 for mammogram (women) and physical examination (men) and data from 1994 for prostate specific antigen test (men) due to the first availability of the data.
During up to 26 years of follow-up of 68,327 women and 44,664 men, we identified 15,103 and 7,366 cancers in women and men, respectively. In the pooled analyses of women and men, mushroom consumption was not related to risk of total cancer (Table 2). Compared to participants who almost never consumed mushrooms, those who consumed 5 or more servings of mushrooms/week had no significantly different risk of total cancer (HR=1.06, 95% CI=0.98–1.14). Increasing mushroom intake by 2 servings/week was not significantly associated with risk of total cancer (HR=1.02, 95% CI=0.97–1.07). When site-specific cancers were separately examined, we found no associations of mushroom consumption with risks of colorectal, lymphoma, bladder, pancreatic, kidney, leukemia, multiple myeloma, brain, oral, stomach, esophageal, and liver cancers. Sex-specific cancers including breast, endometrial, ovarian and advanced prostate cancers were not associated with mushroom consumption either. However, there was a marginal positive association between mushroom consumption and risk of lung cancer (HR per 2 servings/week increase=1.17, 95% CI=1.00–1.36, P for trend=0.05).
Table 2.
Mushroom consumption and risk of total and site-specific cancer (NHS, 1986–2012; HPFS, 1986–2012)
| Frequency of mushroom consumption, per serving |
Per 2/week increase | P-trend | |||||
|---|---|---|---|---|---|---|---|
| Never or almost never | <1/week | 1/week | 2–4/week | 5+/week | |||
| Total cancer (n=22469)a,b | |||||||
| Event | 4981 | 7688 | 5938 | 3009 | 853 | ||
| Person years | 516441 | 803462 | 631961 | 310373 | 84651 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.04 (1.01, 1.08) | 1.05 (1.01, 1.09) | 1.06 (1.01, 1.11) | 1.08 (1.00, 1.16) | 1.03 (0.98, 1.08) | 0.21 |
| Multivariable HR (95% CI) | 1 (ref) | 1.03 (1.00, 1.07) | 1.04 (1.00, 1.08) | 1.04 (0.99, 1.09) | 1.06 (0.98, 1.14) | 1.02 (0.97, 1.07) | 0.55 |
| Cancer sites b | |||||||
| Colorectal cancer (n=2342) | |||||||
| Event | 553 | 793 | 647 | 281 | 68 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.98 (0.88, 1.10) | 1.08 (0.96, 1.21) | 0.92 (0.79, 1.06) | 0.87 (0.67, 1.12) | 0.90 (0.75, 1.07) | 0.24 |
| Multivariable HR (95% CI) | 1 (ref) | 0.97 (0.87, 1.09) | 1.06 (0.94, 1.19) | 0.89 (0.76, 1.04) | 0.85 (0.65, 1.10) | 0.88 (0.73, 1.06) | 0.17 |
| Lung cancer (n=2036) | |||||||
| Event | 414 | 761 | 521 | 264 | 76 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.26 (1.12, 1.43) | 1.15 (1.01, 1.31) | 1.16 (1.00, 1.36) | 1.25 (0.98, 1.60) | 1.09 (0.94, 1.27) | 0.25 |
| Multivariable HR (95% CI) | 1 (ref) | 1.25 (1.11, 1.42) | 1.19 (1.04, 1.37) | 1.26 (1.07, 1.48) | 1.36 (1.05, 1.76) | 1.17 (1.00, 1.36) | 0.05 |
| Lymphoma (n=1456) | |||||||
| Event | 306 | 518 | 369 | 207 | 56 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.13 (0.98, 1.30) | 1.06 (0.91, 1.23) | 1.18 (0.99, 1.41) | 1.23 (0.92, 1.64) | 1.12 (0.94, 1.33) | 0.19 |
| Multivariable HR (95% CI) | 1 (ref) | 1.12 (0.97, 1.30) | 1.06 (0.91, 1.25) | 1.20 (1.00, 1.45) | 1.25 (0.93, 1.69) | 1.13 (0.95, 1.35) | 0.18 |
| Bladder cancer (n=1001) | |||||||
| Event | 214 | 368 | 258 | 128 | 33 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.18 (0.99, 1.40) | 1.13 (0.94, 1.36) | 1.11 (0.89, 1.38) | 1.24 (0.85, 1.79) | 1.15 (0.91, 1.44) | 0.25 |
| Multivariable HR (95% CI) | 1 (ref) | 1.14 (0.96, 1.35) | 1.13 (0.93, 1.37) | 1.14 (0.90, 1.44) | 1.29 (0.88, 1.89) | 1.18 (0.94, 1.49) | 0.15 |
| Pancreatic cancer (n=561) | |||||||
| Event | 124 | 211 | 136 | 77 | 13 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.14 (0.91, 1.43) | 1.01 (0.79, 1.29) | 1.15 (0.86, 1.53) | 0.80 (0.45, 1.42) | 0.94 (0.66, 1.35) | 0.76 |
| Multivariable HR (95% CI) | 1 (ref) | 1.14 (0.91, 1.43) | 0.99 (0.77, 1.28) | 1.10 (0.81, 1.49) | 0.76 (0.42, 1.38) | 0.90 (0.61, 1.33) | 0.61 |
| Kidney cancer (n=545)d | |||||||
| Event | 128 | 184 | 146 | 76 | 11 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.91 (0.73, 1.14) | 0.98 (0.77, 1.24) | 0.99 (0.74, 1.31) | 0.56 (0.30, 1.05) | 0.77 (0.51, 1.17) | 0.22 |
| Multivariable HR (95% CI) | 1 (ref) | 0.94 (0.75, 1.19) | 1.05 (0.82, 1.35) | 1.10 (0.81, 1.49) | 0.66 (0.35, 1.24) | 0.89 (0.58, 1.35) | 0.57 |
| Leukemia (n=386) | |||||||
| Event | 93 | 151 | 84 | 43 | 15 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.09 (0.84, 1.42) | 0.82 (0.60, 1.10) | 0.86 (0.60, 1.25) | 1.26 (0.73, 2.20) | 0.88 (0.54, 1.41) | 0.59 |
| Multivariable HR (95% CI) | 1 (ref) | 1.07 (0.82, 1.40) | 0.79 (0.58, 1.07) | 0.82 (0.56, 1.21) | 1.15 (0.65, 2.05) | 0.83 (0.49, 1.38) | 0.47 |
| Multiple myeloma (n=334) | |||||||
| Event | 77 | 104 | 100 | 43 | 10 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.91 (0.68, 1.23) | 1.17 (0.87, 1.58) | 1.01 (0.69, 1.47) | 0.93 (0.48, 1.81) | 0.90 (0.56, 1.44) | 0.66 |
| Multivariable HR (95% CI) | 1 (ref) | 0.92 (0.68, 1.25) | 1.21 (0.88, 1.65) | 1.07 (0.72, 1.59) | 1.01 (0.51, 2.01) | 0.93 (0.58, 1.49) | 0.76 |
| Brain cancer (n=270) | |||||||
| Event | 61 | 89 | 72 | 36 | 12 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.00 (0.72, 1.39) | 1.05 (0.74, 1.48) | 1.01 (0.67, 1.54) | 1.41 (0.75, 2.64) | 1.36 (0.96, 1.94) | 0.09 |
| Multivariable HR (95% CI) | 1 (ref) | 1.03 (0.74, 1.44) | 1.07 (0.74, 1.53) | 1.03 (0.66, 1.60) | 1.43 (0.74, 2.75) | 1.37 (0.95, 1.97) | 0.09 |
| Oral cancer (n=214) | |||||||
| Event | 52 | 74 | 50 | 33 | 5 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.94 (0.65, 1.34) | 0.83 (0.56, 1.24) | 1.13 (0.73, 1.76) | 0.65 (0.25, 1.65) | 0.84 (0.44, 1.62) | 0.61 |
| Multivariable HR (95% CI) | 1 (ref) | 0.93 (0.64, 1.34) | 0.83 (0.55, 1.25) | 1.17 (0.73, 1.88) | 0.68 (0.26, 1.79) | 0.88 (0.45, 1.71) | 0.71 |
| Stomach cancer (n=203) | |||||||
| Event | 46 | 72 | 55 | 22 | 8 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.10 (0.75, 1.60) | 1.14 (0.76, 1.69) | 0.91 (0.54, 1.52) | 1.30 (0.61, 2.78) | 0.99 (0.58, 1.69) | 0.97 |
| Multivariable HR (95% CI) | 1 (ref) | 1.12 (0.76, 1.64) | 1.16 (0.77, 1.77) | 0.96 (0.56, 1.64) | 1.37 (0.62, 3.02) | 1.00 (0.59, 1.68) | 0.99 |
| Esophageal (n=199) | |||||||
| Event | 53 | 65 | 43 | 34 | 4 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.81 (0.56, 1.18) | 0.75 (0.50, 1.14) | 1.18 (0.76, 1.83) | 0.65 (0.23, 1.82) | 0.97 (0.52, 1.83) | 0.93 |
| Multivariable HR (95% CI) | 1 (ref) | 0.74 (0.51, 1.08) | 0.69 (0.45, 1.06) | 1.09 (0.68, 1.73) | 0.57 (0.20, 1.64) | 0.90 (0.45, 1.80) | 0.77 |
| Liver cancer (n=113) | |||||||
| Event | 22 | 32 | 36 | 17 | 6 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.95 (0.55, 1.65) | 1.58 (0.92, 2.71) | 1.44 (0.76, 2.74) | 2.14 (0.85, 5.34) | 1.54 (0.96, 2.46) | 0.07 |
| Multivariable HR (95% CI) | 1 (ref) | 1.05 (0.60, 1.84) | 1.85 (1.05, 3.25) | 1.67 (0.84, 3.33) | 2.40 (0.91, 6.33) | 1.66 (0.99, 2.77) | 0.05 |
| Sex-specific cancer sitesc | |||||||
| Breast cancer (n=5397) | |||||||
| Event | 1148 | 1818 | 1466 | 753 | 212 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.08 (1.00, 1.16) | 1.07 (0.99, 1.15) | 1.11 (1.01, 1.22) | 0.98 (0.84, 1.13) | 1.00 (0.91, 1.09) | 0.93 |
| Multivariable HR (95% CI) | 1 (ref) | 1.04 (0.96, 1.12) | 1.01 (0.93, 1.09) | 1.03 (0.93, 1.13) | 0.89 (0.77, 1.04) | 0.93 (0.84, 1.03) | 0.19 |
| Endometrial cancer (n=1065) | |||||||
| Event | 242 | 331 | 297 | 133 | 62 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.92 (0.78, 1.09) | 1.02 (0.86, 1.21) | 0.92 (0.74, 1.14) | 1.32 (1.00, 1.75) | 1.12 (0.93, 1.36) | 0.22 |
| Multivariable HR (95% CI) | 1 (ref) | 0.91 (0.77, 1.08) | 0.98 (0.82, 1.17) | 0.83 (0.66, 1.04) | 1.16 (0.86, 1.56) | 1.03 (0.84, 1.26) | 0.77 |
| Ovarian cancer (n=550) | |||||||
| Event | 140 | 178 | 138 | 73 | 21 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.86 (0.69, 1.07) | 0.83 (0.65, 1.05) | 0.90 (0.68, 1.20) | 0.81 (0.51, 1.29) | 0.85 (0.60, 1.21) | 0.36 |
| Multivariable HR (95% CI) | 1 (ref) | 0.83 (0.66, 1.04) | 0.83 (0.65, 1.06) | 0.95 (0.70, 1.28) | 0.87 (0.54, 1.40) | 0.92 (0.65, 1.31) | 0.66 |
| Advanced prostate cancer (n=956) | |||||||
| Event | 228 | 342 | 244 | 117 | 25 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.07 (0.90, 1.27) | 1.15 (0.96, 1.38) | 1.04 (0.83, 1.30) | 1.10 (0.72, 1.66) | 1.05 (0.81, 1.36) | 0.72 |
| Multivariable HR (95% CI) | 1 (ref) | 1.07 (0.90, 1.27) | 1.15 (0.95, 1.39) | 1.01 (0.80, 1.29) | 1.06 (0.69, 1.63) | 1.02 (0.77, 1.35) | 0.89 |
Abbreviation: HPFS, health professionals follow-up study; NHS, nurses’ health study.
Age-adjusted models included age (months).
Multivariable models included for age, race (white or non-white), height (continuous), body mass index (quintiles), family history of cancer (yes or no), physical exam in past two years (yes or no), history of colonoscopy or sigmoidoscopy (yes or no), smoking in pack years (never smoker, 1–4.9, 5–19.9, 20–39.9, or ≥40), physical activity (quintiles), regular aspirin use (yes or no), multivitamin use (yes or no), total energy intake (quintiles), alcohol consumption (0, 0.1–4.9, 5.0–14.9, 15.0–29.9, or ≥30 g/d), red and processed meat intake (quintiles), Prudent diet pattern (quintiles) and Western diet pattern (quintiles); prostate specific antigen test in past two years (yes or no) (men only); and menopause status (pre-menopause or post-menopause), postmenopausal hormone use (never, past, or current), and mammogram in past two years (yes or no) (women only).
included only aggressive prostate cancer as total cancer.
Pooled results of women and men.
Sex-specific results of women (breast, endometrial, and ovarian cancers) and men (advanced prostate cancer).
We then evaluated the relation of mushroom intake and cancer risk within strata of smoking status (Table 3). In these analyses, we also found no association between mushroom consumption and total and most of site-specific cancers regardless of smoking status. However, we still observed a suggestive positive association between mushroom consumption and lung cancer risk in both ever smokers (P for trend=0.05) and never smokers (P for trend=0.004). These associations were not statistically significant after adjustment of multiple comparisons (Bonferroni-corrected P<0.0028). Additional analyses stratified by other health behaviors including recency of physical examination, physical activity, and dietary patterns did not change the overall results.
Table 3.
Mushroom consumption and risk of total and site-specific cancer by smoking status (NHS, 1986–2012; HPFS, 1986–2012)
| Frequency of mushroom consumption, per serving |
Per 2/week increase | P-trend | |||||
|---|---|---|---|---|---|---|---|
| Never or almost never | <1/week | 1/week | 2–4/week | 5+/week | |||
| Total cancera,b | |||||||
| Ever smokers(n=13365) | 1 (ref) | 1.03 (1.00, 1.07) | 1.04 (1.00, 1.08) | 1.04 (0.99, 1.09) | 1.06 (0.98, 1.14) | 1.02 (0.97, 1.07) | 0.54 |
| Never smokers (n=9104) | 1 (ref) | 1.04 (1.00, 1.08) | 1.05 (1.01, 1.09) | 1.06 (1.01, 1.11) | 1.08 (1.00, 1.16) | 1.03 (0.98, 1.08) | 0.28 |
| Cancer sitesb | |||||||
| Colorectal cancer | |||||||
| Ever smokers (n=1376) | 1 (ref) | 0.97 (0.87, 1.09) | 1.06 (0.94, 1.19) | 0.89 (0.76, 1.04) | 0.85 (0.65, 1.10) | 0.88 (0.73, 1.06) | 0.17 |
| Never smokers (n=966) | 1 (ref) | 0.98 (0.87, 1.09) | 1.06 (0.94, 1.20) | 0.90 (0.77, 1.05) | 0.86 (0.66, 1.12) | 0.89 (0.74, 1.07) | 0.21 |
| Lung cancer | |||||||
| Ever smokers (n=1732) | 1 (ref) | 1.25 (1.11, 1.42) | 1.19 (1.04, 1.37) | 1.26 (1.07, 1.48) | 1.36 (1.05, 1.76) | 1.17 (1.00, 1.36) | 0.05 |
| Never smokers (n=304) | 1 (ref) | 1.29 (1.14, 1.46) | 1.28 (1.11, 1.46) | 1.37 (1.16, 1.62) | 1.56 (1.21, 2.02) | 1.24 (1.07, 1.42) | 0.004 |
| Lymphoma | |||||||
| Ever smokers (n=762) | 1 (ref) | 1.12 (0.97, 1.30) | 1.06 (0.91, 1.25) | 1.20 (0.99, 1.45) | 1.25 (0.93, 1.68) | 1.13 (0.94, 1.34) | 0.19 |
| Never smokers (n=694) | 1 (ref) | 1.12 (0.97, 1.30) | 1.07 (0.91, 1.25) | 1.20 (1.00, 1.45) | 1.26 (0.93, 1.69) | 1.13 (0.95, 1.35) | 0.18 |
| Bladder cancer | |||||||
| Ever smokers (n=682) | 1 (ref) | 1.14 (0.96, 1.35) | 1.13 (0.93, 1.37) | 1.14 (0.90, 1.44) | 1.29 (0.88, 1.89) | 1.18 (0.94, 1.49) | 0.15 |
| Never smokers (n=319) | 1 (ref) | 1.15 (0.97, 1.37) | 1.16 (0.96, 1.40) | 1.18 (0.93, 1.49) | 1.37 (0.93, 2.01) | 1.23 (0.98, 1.54) | 0.08 |
| Pancreatic cancer | |||||||
| Ever smokers (n=328) | 1 (ref) | 1.14 (0.91, 1.43) | 0.99 (0.76, 1.28) | 1.10 (0.81, 1.49) | 0.76 (0.42, 1.37) | 0.90 (0.61, 1.33) | 0.61 |
| Never smokers (n=233) | 1 (ref) | 1.14 (0.90, 1.43) | 0.99 (0.77, 1.28) | 1.10 (0.81, 1.49) | 0.77 (0.43, 1.39) | 0.91 (0.62, 1.34) | 0.64 |
| Kidney cancer | |||||||
| Ever smokers (n=299) | 1 (ref) | 0.94 (0.75, 1.19) | 1.05 (0.82, 1.35) | 1.10 (0.81, 1.49) | 0.66 (0.35, 1.24) | 0.89 (0.58, 1.35) | 0.57 |
| Never smokers (n=246) | 1 (ref) | 0.95 (0.75, 1.19) | 1.06 (0.83, 1.36) | 1.12 (0.82, 1.51) | 0.67 (0.36, 1.26) | 0.90 (0.60, 1.37) | 0.63 |
| Leukemia | |||||||
| Ever smokers (n=215) | 1 (ref) | 1.07 (0.82, 1.40) | 0.79 (0.58, 1.07) | 0.82 (0.56, 1.21) | 1.15 (0.65, 2.04) | 0.83 (0.49, 1.38) | 0.47 |
| Never smokers (n=171) | 1 (ref) | 1.07 (0.82, 1.40) | 0.78 (0.57, 1.07) | 0.82 (0.56, 1.21) | 1.16 (0.65, 2.06) | 0.83 (0.50, 1.39) | 0.48 |
| Multiple myeloma | |||||||
| Ever smokers (n=185) | 1 (ref) | 0.92 (0.68, 1.25) | 1.21 (0.88, 1.66) | 1.07 (0.72, 1.59) | 1.03 (0.52, 2.05) | 0.94 (0.59, 1.50) | 0.79 |
| Never smokers (n=149) | 1 (ref) | 0.92 (0.68, 1.25) | 1.21 (0.88, 1.66) | 1.07 (0.72, 1.59) | 1.03 (0.52, 2.04) | 0.94 (0.58, 1.50) | 0.78 |
| Brain cancer | |||||||
| Ever smokers (n=139) | 1 (ref) | 1.03 (0.74, 1.44) | 1.08 (0.75, 1.54) | 1.03 (0.66, 1.60) | 1.44 (0.75, 2.78) | 1.37 (0.96, 1.97) | 0.09 |
| Never smokers (n=131) | 1 (ref) | 1.03 (0.74, 1.44) | 1.07 (0.75, 1.54) | 1.03 (0.66, 1.59) | 1.45 (0.75, 2.78) | 1.36 (0.95, 1.95) | 0.09 |
| Oral cancer | |||||||
| Ever smokers (n=132) | 1 (ref) | 0.93 (0.64, 1.34) | 0.83 (0.55, 1.25) | 1.18 (0.73, 1.89) | 0.68 (0.26, 1.79) | 0.88 (0.46, 1.71) | 0.71 |
| Never smokers (n=82) | 1 (ref) | 0.93 (0.64, 1.33) | 0.84 (0.56, 1.27) | 1.18 (0.74, 1.89) | 0.69 (0.26, 1.82) | 0.90 (0.46, 1.75) | 0.76 |
| Stomach cancer | |||||||
| Ever smokers (n=115) | 1 (ref) | 1.12 (0.76, 1.64) | 1.16 (0.77, 1.77) | 0.96 (0.56, 1.64) | 1.37 (0.62, 3.01) | 1.00 (0.59, 1.68) | 0.99 |
| Never smokers (n=88) | 1 (ref) | 1.13 (0.77, 1.66) | 1.18 (0.78, 1.79) | 0.97 (0.57, 1.67) | 1.40 (0.64, 3.10) | 1.02 (0.60, 1.72) | 0.94 |
| Esophageal | |||||||
| Ever smokers (n=145) | 1 (ref) | 0.74 (0.51, 1.08) | 0.69 (0.45, 1.06) | 1.09 (0.68, 1.73) | 0.57 (0.20, 1.64) | 0.90 (0.45, 1.80) | 0.77 |
| Never smokers (n=54) | 1 (ref) | 0.76 (0.52, 1.11) | 0.70 (0.46, 1.08) | 1.11 (0.70, 1.78) | 0.61 (0.22, 1.75) | 0.94 (0.47, 1.86) | 0.85 |
| Liver cancer | |||||||
| Ever smokers (n=65) | 1 (ref) | 1.05 (0.60, 1.84) | 1.85 (1.05, 3.25) | 1.68 (0.84, 3.34) | 2.39 (0.91, 6.32) | 1.67 (1.00, 2.79) | 0.05 |
| Never smokers (n=48) | 1 (ref) | 1.06 (0.61, 1.86) | 1.86 (1.06, 3.28) | 1.69 (0.85, 3.37) | 2.45 (0.93, 6.47) | 1.67 (1.00, 2.79) | 0.05 |
| Sex-specific cancer sitesc | |||||||
| Breast cancer | |||||||
| Ever smokers (n=2947) | 1 (ref) | 1.11 (1.00, 1.24) | 1.09 (0.97, 1.22) | 1.08 (0.94, 1.23) | 0.88 (0.72, 1.09) | 0.92 (0.81, 1.06) | 0.24 |
| Never smokers (n=2450) | 1 (ref) | 0.96 (0.86, 1.07) | 0.91 (0.81, 1.03) | 0.99 (0.86, 1.15) | 0.96 (0.76, 1.21) | 0.98 (0.83, 1.15) | 0.78 |
| Endometrial cancer | |||||||
| Ever smokers (n=516) | 1 (ref) | 0.84 (0.65, 1.09) | 0.98 (0.75, 1.27) | 0.81 (0.58, 1.11) | 1.28 (0.86, 1.89) | 1.07 (0.83, 1.39) | 0.60 |
| Never smokers (n=549) | 1 (ref) | 0.98 (0.79, 1.24) | 0.97 (0.75, 1.24) | 0.86 (0.63, 1.19) | 0.96 (0.59, 1.54) | 0.96 (0.67, 1.36) | 0.81 |
| Ovarian cancer | |||||||
| Ever smokers (n=323) | 1 (ref) | 1.05 (0.77, 1.43) | 0.91 (0.65, 1.28) | 1.08 (0.72, 1.62) | 0.90 (0.48, 1.68) | 0.92 (0.60, 1.42) | 0.72 |
| Never smokers (n=227) | 1 (ref) | 0.60 (0.42, 0.85) | 0.74 (0.51, 1.07) | 0.83 (0.52, 1.33) | 0.88 (0.41, 1.88) | 0.91 (0.51, 1.64) | 0.76 |
| Advanced prostate cancer | |||||||
| Ever smokers (n=497) | 1 (ref) | 0.99 (0.78, 1.26) | 0.98 (0.75, 1.29) | 1.10 (0.79, 1.52) | 1.03 (0.58, 1.84) | 1.12 (0.79, 1.58) | 0.53 |
| Never smokers (n=459) | 1 (ref) | 1.20 (0.93, 1.55) | 1.31 (0.99, 1.73) | 0.92 (0.64, 1.34) | 1.00 (0.50, 1.98) | 0.82 (0.49, 1.39) | 0.47 |
All models included for age, race (white or non-white), height (continuous), body mass index (quintiles), family history of cancer (yes or no), physical exam in past two years (yes or no), history of colonoscopy or sigmoidoscopy (yes or no), smoking in pack years (never smoker, 1–4.9, 5–19.9, 20–39.9, or ≥40), physical activity (quintiles), regular aspirin use (yes or no), multivitamin use (yes or no), total energy intake (quintiles), alcohol consumption (0, 0.1–4.9, 5.0–14.9, 15.0–29.9, or ≥30 g/d), red and processed meat intake (quintiles), Prudent diet pattern (quintiles) and Western diet pattern (quintiles); prostate specific antigen test in past two years (yes or no) (men only); and menopause status (pre-menopause or post-menopause), postmenopausal hormone use (never, past, or current), and mammogram in past two years (yes or no) (women only).
included only aggressive prostate cancer as total cancer.
Pooled results of women and men.
Sex-specific results of women (breast, endometrial, and ovarian cancers) and men (advanced prostate cancer).
When we stratified by sex, we observed no associations between mushroom consumption and total cancer risk in women (HR per 2 servings/week increase=0.98, 95% CI=0.93–1.04) (Supplemental Table 1). Moreover, mushroom consumption was not associated with any site-specific cancers in women. In men, we found a marginal positive association of mushroom consumption with risk of total cancer (HR per 2 servings/week increase=1.10, 95% CI=1.00–1.21, P for trend=0.04) and liver cancer (HR per 2 servings/week increase=2.13, 95% CI=1.12–4.05, P for trend=0.02). These associations were not statistically significant after adjusting for multiple comparison (Supplemental Table 2). Other cancer sites were not associated with mushroom consumption in men.
Discussion
In the two large US prospective cohorts, we found no association between mushroom consumption and total cancer risk. Moreover, mushroom consumption was not associated with 16 site-specific cancers including both major and relatively rare cancers. However, there was a marginal positive association between mushroom consumption and lung cancer risk, which persisted among participants who never smoked.
Although in vitro and animal studies have found the potential benefit of mushrooms on carcinogenesis,(6,7) few studies have evaluated this relation in humans. The existing epidemiologic evidence is largely from small retrospective case-control studies (<500 cases) that examined the association between mushroom consumption and risk of breast cancer. A dose-response meta-analysis of 7 studies, including 5 case-control and 2 cohort studies, reported that increasing 1 gram per day of mushrooms is associated with 3% decreased risk of breast cancer (RR=0.97, 95% CI=0.96–0.98) with moderate heterogeneity (I2=56.3%, P=0.015).(8) Due to small number of studies and lack of detailed information, this meta-analysis could not identify the source of heterogeneity.
Beside breast cancer, several studies have examined the association between mushroom consumption and risk of other cancer sites. Two small hospital-based case-control studies from Asia showed some evidence that high mushroom consumption may reduce stomach cancer risk.(15,16) A Korean study that examined the role of multiple dietary factors on stomach cancer found that participants with high mushroom consumption (>75th percentile) had 70% decreased risk of stomach cancer, compared to those with low mushroom consumption (<25th percentile) (RR=0.30, 95% CI=0.15–0.62, P for trend<0.001).(16) Similarly, a Japanese study showed an inverse, but marginally significant, association of specific type of mushrooms (Hypsizigus marmoreus and Pholiota nameko) with stomach cancer risk, particularly cardia cancer.(15) Moreover, two large cohort studies of Chinese women and men in urban Shanghai investigated the role of dietary patterns and specific food groups on liver cancer risk.(17) This study suggested that a vegetable-based dietary pattern was associated with reduced risk of liver cancer. Additional analyses of individual food groups showed that high consumption of mushrooms and several other foods (e.g., celery, allium and composite vegetables, legumes and legume products) were associated with decreased risk of liver cancer. Compared to those in the lowest quartile, participants in the highest quartile of mushroom consumption had 34% lower risk of liver cancer (RR=0.66, 95% CI=0.46–0.95, P for trend=0.03) after adjustment for dietary pattern. Unlike stomach and liver cancers, a couple of studies that examined other cancer sites found no association between mushroom consumption and cancers of colorectum(15) and prostate.(18)
Overall findings of the previous studies were not consistent with our study which showed no evident association between mushroom consumption and risk of total and site-specific cancers. There are several potential reasons for why we see overall null results. First of all, compared to prospective cohort studies,(19,20) retrospective case-control studies(21–25) tended to show a significant or suggestive inverse association between mushroom consumption and breast cancer risk. Of note, other types of cancer did not have sufficient number of studies to compare between study design. Case-control studies are prone to recall bias, meaning that patients with cancer may underreport their mushroom consumption knowing that mushrooms are generally considered as a healthy food.(26) In this case, high intake of mushrooms would appear to be beneficial to reduce cancer risk. Moreover, selection bias in retrospective case-control studies, especially hospital-based, is another source of bias that may affect the results.(27) Second, the majority of case-control studies were from Asian countries including Korea, China, and Japan.(15,16,21–25) In contrast, only a few studies were done in non-Asian populations in Europe and they were mostly cohort studies.(18–20) In Asian countries, mushrooms are more commonly consumed and various types of edible mushrooms, including medicinal mushrooms, are widely available. In fact, Asian studies generally had higher average and larger variation in mushroom consumption compared to non-Asian studies. If a dose-response relationship exists, the true association may have been masked in populations with limited range of mushroom consumption.(28) Moreover, most studies, including our study, did not have detailed information on types of mushrooms thus we are examining the combined association of all edible mushrooms on cancer risk. Cultural differences related to types of mushrooms may affect the association, if different types of mushrooms have different effects on cancer development. Given the growing interests in medicinal mushrooms, further epidemiologic studies and trials are needed to discover the potential anticancer effect of certain types of mushrooms.
While we observed no relation with total cancer and with most of the sites examined, we did observe a positive relation with lung cancer that was stronger among never smokers, as well as a positive association with liver cancer restricted to men. It is important to consider the possibility that these results may represent chance findings. Previous cohort studies that reported a suggestive inverse association between mushrooms and risk of a certain cancer may have had multiple testing issues.(14) Interestingly, all cohort studies we found had examined various diets in relation to cancer risk and thus among many food items, mushrooms may have shown to be statistically significant by chance.(17–20) Similarly, although our study examined one primary exposure (mushrooms), we had multiple outcomes (total and 17 cancer sites). Therefore, the observed positive associations of mushrooms with risk of lung (pooled data only) and liver (men data only) cancers could be due to chance, especially when considering the lack of convincing a priori hypothesis for these two sites. Moreover, when multiple comparisons were accounted for, mushroom consumption was not associated with any cancer sites.
Our study has considerable strengths. To our knowledge, this is the first and the largest prospective study to examine the association between mushroom consumption and cancer risk. During 26 years of follow-up, we collected sufficient number of cancer cases which allowed us to examine most major cancers and some rare cancers (17 cancer sites). We had detailed and repeated information on lifestyle factors and medical history over the follow-up to finely control for potential confounders. There are several limitations as well. First, mushroom consumption was assessed only once at baseline using FFQ. Thus, single measure may not reflect the long-term mushroom consumption but the measurement error is likely to be non-differential, which yields more conservative results. Second, detailed information on types of mushrooms were not reported. Some types of mushrooms (e.g., medicinal mushrooms) may have different effect on cancer risk. Third, our cohorts consisted of White health professionals which strengthens the internal validity but may limit the generalizability of our findings.
In conclusion, we found no association of mushroom consumption with total and site-specific cancers in US women and men. These findings suggest that the cancer-protective effects of mushrooms described in in vitro and animal studies are likely to have minimal impact in terms of cancer prevention at a population level. Given that the most salient limitations of this study are the lack of specificity in mushroom assessment (i.e., variety of specific mushroom species, cultivation and cooking practices), the lack of repeated measures of mushroom intake over time, and the lack of racial/ethnic diversity of the study population, future studies revisiting this hypothesis should ideally address these three issues.
Supplementary Material
Acknowledgements
We thank the participants and staff of the NHS and HPFS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.
Source of financial support: This work was supported by grants from the National Institute of Health (UM1 CA186107, R01 HL034594, R01 HL088521, UM1 CA167552, and R01 HL035464) and a grant from Horticulture Australia Limited (HAL). HAL had no role in study planning, data collection, data analysis, interpretation of the findings, drafting of the manuscript or decisions regarding where or when to publish study results. NK was supported by funding from the National Research Foundation of Korea (NRF-2018R1A4A1022589).
Footnotes
Conflict of interest: All authors declare no conflicts of interest.
References
- 1.Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2018. [DOI] [PubMed] [Google Scholar]
- 2.Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, et al. The global burden of cancer 2013. JAMA oncology 2015;1(4):505–27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical research 2008;25(9):2097–116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.World Cancer Research Fund AIfCRD, nutrition, physical activity and cancer: a global perspective. https://www.wcrf.org/dietandcancer. Accessed 11 Oct 2018.
- 5.Chatterjee B, Patel T. Edible mushroom–a nutritious food improving human health. 2016.
- 6.Roupas P, Keogh J, Noakes M, Margetts C, Taylor P. The role of edible mushrooms in health: Evaluation of the evidence. Journal of Functional Foods 2012;4(4):687–709. [Google Scholar]
- 7.Sullivan R, Smith JE, Rowan NJ. Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine. Perspectives in biology and medicine 2006;49(2):159–70. [DOI] [PubMed] [Google Scholar]
- 8.Li J, Zou L, Chen W, Zhu B, Shen N, Ke J, et al. Dietary mushroom intake may reduce the risk of breast cancer: evidence from a meta-analysis of observational studies. PloS one 2014;9(4):e93437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Yuan C, Spiegelman D, Rimm EB, Rosner BA, Stampfer MJ, Barnett JB, et al. Relative Validity of Nutrient Intakes Assessed by Questionnaire, 24-Hour Recalls, and Diet Records as Compared With Urinary Recovery and Plasma Concentration Biomarkers: Findings for Women. American journal of epidemiology 2018;187(5):1051–63 doi 10.1093/aje/kwx328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Yuan C, Spiegelman D, Rimm EB, Rosner BA, Stampfer MJ, Barnett JB, et al. Validity of a Dietary Questionnaire Assessed by Comparison With Multiple Weighed Dietary Records or 24-Hour Recalls. American journal of epidemiology 2017;185(7):570–84 doi 10.1093/aje/kww104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Feskanich D, Rimm EB, Giovannucci EL, Colditz GA, Stampfer MJ, Litin LB, et al. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. Journal of the American Dietetic Association 1993;93(7):790–6. [DOI] [PubMed] [Google Scholar]
- 12.Salvini S, Hunter DJ, Sampson L, Stampfer MJ, Colditz GA, Rosner B, et al. Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. International journal of epidemiology 1989;18(4):858–67. [DOI] [PubMed] [Google Scholar]
- 13.Hu FB, Rimm E, Smith-Warner SA, Feskanich D, Stampfer MJ, Ascherio A, et al. Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire. The American journal of clinical nutrition 1999;69(2):243–9. [DOI] [PubMed] [Google Scholar]
- 14.Bender R, Lange S. Adjusting for multiple testing—when and how? Journal of clinical epidemiology 2001;54(4):343–9. [DOI] [PubMed] [Google Scholar]
- 15.Hara M, Hanaoka T, Kobayashi M, Otani T, Adachi HY, Montani A, et al. Cruciferous vegetables, mushrooms, and gastrointestinal cancer risks in a multicenter, hospital-based case-control study in Japan. Nutrition and cancer 2003;46(2):138–47. [DOI] [PubMed] [Google Scholar]
- 16.Kim HJ, Chang WK, Kim MK, Lee SS, Choi BY. Dietary factors and gastric cancer in Korea: A case‐control study. International journal of cancer 2002;97(4):531–5. [DOI] [PubMed] [Google Scholar]
- 17.Zhang W, Xiang YB, Li HL, Yang G, Cai H, Ji BT, et al. Vegetable‐based dietary pattern and liver cancer risk: Results from the S hanghai W omen’s and M en’s H ealth S tudies. Cancer science 2013;104(10):1353–61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Schuurman AG, Goldbohm RA, Dorant E, van den Brandt PA. Vegetable and fruit consumption and prostate cancer risk: a cohort study in The Netherlands. Cancer Epidemiology and Prevention Biomarkers 1998;7(8):673–80. [PubMed] [Google Scholar]
- 19.Masala G, Assedi M, Bendinelli B, Ermini I, Sieri S, Grioni S, et al. Fruit and vegetables consumption and breast cancer risk: the EPIC Italy study. Breast cancer research and treatment 2012;132(3):1127–36. [DOI] [PubMed] [Google Scholar]
- 20.Van Gils CH, Peeters PH, Bueno-de-Mesquita HB, Boshuizen HC, Lahmann PH, Clavel-Chapelon F, et al. Consumption of vegetables and fruits and risk of breast cancer. Jama 2005;293(2):183–93. [DOI] [PubMed] [Google Scholar]
- 21.Hong SA, Kim K, Nam SJ, Kong G, Kim MK. A case–control study on the dietary intake of mushrooms and breast cancer risk among Korean women. International journal of cancer 2008;122(4):919–23. [DOI] [PubMed] [Google Scholar]
- 22.Mizoo T, Taira N, Nishiyama K, Nogami T, Iwamoto T, Motoki T, et al. Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case–control study in Japanese women. BMC cancer 2013;13(1):565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Shin A, Kim J, Lim S-Y, Kim G, Sung M-K, Lee E-S, et al. Dietary mushroom intake and the risk of breast cancer based on hormone receptor status. Nutrition and cancer 2010;62(4):476–83. [DOI] [PubMed] [Google Scholar]
- 24.Zhang CX, Ho SC, Chen YM, Fu JH, Cheng SZ, Lin FY. Greater vegetable and fruit intake is associated with a lower risk of breast cancer among Chinese women. International journal of cancer 2009;125(1):181–8. [DOI] [PubMed] [Google Scholar]
- 25.Zhang M, Huang J, Xie X, Holman CAJ. Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women. International journal of cancer 2009;124(6):1404–8. [DOI] [PubMed] [Google Scholar]
- 26.Coughlin SS. Recall bias in epidemiologic studies. Journal of clinical epidemiology 1990;43(1):87–91. [DOI] [PubMed] [Google Scholar]
- 27.Wacholder S, McLaughlin JK, Silverman DT, Mandel JS. Selection of controls in case-control studies: I. Principles. American journal of epidemiology 1992;135(9):1019–28. [DOI] [PubMed] [Google Scholar]
- 28.Willett W Nutritional epidemiology. Oxford University Press; 2012. [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.