Association of folate intake and colorectal cancer risk in the postfortification era in US women

ABSTRACT Background Folate may play a preventive role in the early stages of colorectal carcinogenesis, but long latencies may be needed to observe a reduction in colorectal cancer (CRC) incidence. In addition, concerns have been raised about the potential for cancer promotion with excessive folate intake, especially after the mandatory folic acid fortification in the United States in 1998. Objective We aimed to examine the association between folate intake in different chemical forms and CRC risk, especially in the postfortification era in the United States. Design We prospectively followed 86,320 women from the Nurses’ Health Study (1980–2016). Folate intake was collected by validated food frequency questionnaires. CRC was self reported and confirmed by review of medical records. The association between the folate intake and CRC risk was assessed using Cox proportional hazards regression. Results We documented 1988 incident CRC cases during follow-up. Analyzing folate intake as a continuous variable, greater total folate intake 12–24 y before diagnosis was associated with lower risk of CRC (per increment of 400 dietary folate equivalents (DFE)/d, HR: 0.93, 95% CI: 0.85, 1.01 for 12–16 y; HR: 0.83, 95% CI: 0.75, 0.92 for 16–20 y; and HR: 0.87, 95% CI: 0.77, 0.99 for 20–24 y); and greater synthetic folic acid intake 16–24 y before diagnosis was also associated with a lower CRC risk (per increment of 400 DFE/d, HR: 0.91, 95% CI: 0.84, 0.99 for 16–20 y and HR: 0.91, 95% CI: 0.83–1.01 for 20–24 y). In the postfortification period (1998–2016), intake of total or specific forms of folate was not associated with CRC risk, even among multivitamin users. Conclusions Folate intake, both total and from synthetic forms, was associated with a lower risk of overall CRC after long latency periods. There was no evidence that high folate intake in the postfortification period was related to increased CRC risk in this US female population.

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State Variation in Early-Onset Colorectal Cancer in the United States, 1995–2015

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djz098 ◽

2019 ◽

Vol 111 (10) ◽

pp. 1104-1106 ◽

Cited By ~ 17

Author(s):

Rebecca L Siegel ◽

Genet A Medhanie ◽

Stacey A Fedewa ◽

Ahmedin Jemal

Keyword(s):

Colorectal Cancer ◽

United States ◽

Confidence Interval ◽

Early Onset ◽

Rate Ratio ◽

The United States ◽

Colorectal Carcinogenesis ◽

Obesity Prevalence ◽

Incidence Trends ◽

Early Onset Colorectal Cancer

Abstract The extent to which the increase in early-onset colorectal cancer (CRC) in the United States varies geographically is unknown. We analyzed changes in CRC incidence and risk factors among people aged 20–49 years by state using high-quality population-based cancer registry data provided by the North American Association of Central Cancer Registries and national survey data, respectively. Early-onset CRC incidence was mostly stable among blacks and Hispanics but increased in 40 of 47 states among non-Hispanic whites, most prominently in western states. For example, rates increased in Washington from 6.7 (per 100 000) during 1995–1996 to 11.5 during 2014–2015 (rate ratio = 1.73, 95% confidence interval = 1.48 to 2.01) and in Colorado from 6.0 to 9.5 (rate ratio = 1.57, 95% confidence interval = 1.30 to 1.91). Nevertheless, current CRC incidence was highest in southern states. From 1995 to 2005, increases occurred in obesity prevalence in all states and heavy alcohol consumption in one-third of states, but neither were correlated with CRC incidence trends. Early-onset CRC is increasing most rapidly among whites in western states. Etiologic studies are needed to explore early life colorectal carcinogenesis.

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Prospective study of alcohol consumption and the risk of colorectal cancer before and after folic acid fortification in the United States

Annals of Epidemiology ◽

10.1016/j.annepidem.2013.04.011 ◽

2013 ◽

Vol 23 (9) ◽

pp. 558-563 ◽

Cited By ~ 14

Author(s):

Hongmei Nan ◽

Jung Eun Lee ◽

Eric B. Rimm ◽

Charles S. Fuchs ◽

Edward L. Giovannucci ◽

...

Keyword(s):

Colorectal Cancer ◽

United States ◽

Folic Acid ◽

Alcohol Consumption ◽

Prospective Study ◽

The United States ◽

Folic Acid Fortification ◽

Before And After

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Plasma sex hormones and risk of conventional and serrated precursors of colorectal cancer in postmenopausal women

BMC Medicine ◽

10.1186/s12916-020-01895-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Dong Hang ◽

Xiaosheng He ◽

Ane Sørlie Kværner ◽

Andrew T. Chan ◽

Kana Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Postmenopausal Women ◽

Sex Hormones ◽

Lower Risk ◽

Free Testosterone ◽

Colorectal Carcinogenesis ◽

Sex Hormone Binding Globulin ◽

Health Study ◽

Serrated Polyps ◽

Free Estradiol

Abstract Background Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. Methods We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses’ Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. Results During 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24–0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17–1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02–2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99–1.78, P for trend = 0.03, respectively). Conclusions The findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.

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Prediagnostic Plasma Folate and the Risk of Death in Patients With Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.16.1943 ◽

2008 ◽

Vol 26 (19) ◽

pp. 3222-3228 ◽

Cited By ~ 24

Author(s):

Brian M. Wolpin ◽

Esther K. Wei ◽

Kimmie Ng ◽

Jeffrey A. Meyerhardt ◽

Jennifer A. Chan ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Cox Proportional Hazards ◽

Folate Intake ◽

Health Study ◽

Recent Trial ◽

Risk Of Death ◽

Plasma Folate ◽

Increased Risk ◽

Overall Mortality

Purpose Although previous studies have demonstrated an inverse relationship between folate intake and colorectal cancer risk, a recent trial suggests that supplemental folic acid may accelerate tumorigenesis among patients with a history of colorectal adenoma. Therefore, high priority has been given to research investigating the influence of folate on cancer progression in patients with colorectal cancer. Patients and Methods To investigate whether prediagnostic levels of plasma folate are associated with colorectal cancer–specific and overall mortality, we performed a prospective, nested observational study within two large US cohorts: the Nurses' Health Study and Health Professionals Follow-Up Study. We measured folate levels among 301 participants who developed colorectal cancer 2 or more years after their plasma was collected and compared participants using Cox proportional hazards models by quintile of plasma folate. Results Higher levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality. Compared with participants in the lowest quintile of plasma folate, those in the highest quintile experienced a multivariable-adjusted hazard ratio for colorectal cancer–specific mortality of 0.42 (95% CI, 0.20 0.88) and overall mortality of 0.46 (95% CI, 0.24 0.88). When the analysis was limited to participants whose plasma was collected within 5 years of cancer diagnosis, no detrimental effect of high plasma folate was noted. In subgroup analyses, no subgroup demonstrated worse survival among participants with higher plasma folate levels. Conclusion In two large prospective cohorts, higher prediagnostic levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality.

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Carotenoids, vitamin A, vitamin C, vitamin E, and folate and risk of self-reported hearing loss in women

American Journal of Clinical Nutrition ◽

10.3945/ajcn.115.109314 ◽

2015 ◽

Vol 102 (5) ◽

pp. 1167-1175 ◽

Cited By ~ 23

Author(s):

Sharon G Curhan ◽

Konstantina M Stankovic ◽

Roland D Eavey ◽

Molin Wang ◽

Meir J Stampfer ◽

...

Keyword(s):

Hearing Loss ◽

Vitamin E ◽

Vitamin A ◽

Vitamin C ◽

Lower Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Folate Intake ◽

Health Study ◽

Β Carotene

ABSTRACT Background: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. Objective: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. Design: This prospective cohort study followed 65,521 women in the Nurses’ Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. Results: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of β-carotene and β-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for β-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for β-cryptoxanthin. In comparison with women with folate intake 200–399 μg/d, very low folate intake (<200 μg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake ≥1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. Conclusion: Higher intakes of β-carotene, β-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk.

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Circulating 25-Hydroxyvitamin D Levels and Survival in Patients With Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.1027 ◽

2008 ◽

Vol 26 (18) ◽

pp. 2984-2991 ◽

Cited By ~ 205

Author(s):

Kimmie Ng ◽

Jeffrey A. Meyerhardt ◽

Kana Wu ◽

Diane Feskanich ◽

Bruce W. Hollis ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Colorectal Carcinogenesis ◽

Health Study ◽

Blood Collection ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Overall Mortality

Purpose Higher plasma 25-hydroxyvitamin D3 (25(OH)D) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma 25(OH)D on the outcome of patients with established colorectal cancer is unknown. Patients and Methods We prospectively examined the association between prediagnosis 25(OH)D levels and mortality among 304 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) who were diagnosed with colorectal cancer from 1991 to 2002. Participants diagnosed within 2 years of blood collection were excluded. Patients were observed until death, June 2005 (NHS), or January 2005 (HPFS), whichever came first. The primary end point was overall mortality. Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for other risk factors for cancer survival. Results Higher plasma 25(OH)D levels were associated with a significant reduction in overall mortality (P for trend = .02). Compared with the lowest quartile, participants in the highest quartile had an adjusted HR of 0.52 (95% CI, 0.29 to 0.94) for overall mortality. A trend toward improved colorectal cancer–specific mortality was also seen (HR = 0.61; 95% CI, 0.31 to 1.19). The results remained unchanged after excluding patients diagnosed within 5 years of blood collection (P for trend = .04); the multivariate HR for overall mortality comparing extreme quartiles was 0.45 (95% CI, 0.19 to 1.09). Conclusion Among patients with colorectal cancer, higher prediagnosis plasma 25(OH)D levels were associated with a significant improvement in overall survival. Further study of the vitamin D pathway and its influence on colorectal carcinogenesis and cancer progression is warranted.

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