Folate intake and risk of colorectal cancer and adenoma: Modification by time

Department of Food and Nutrition, Sookmyung Women's University, Seoul, Republic of Korea.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 03/2011; 93(4):817-25. DOI: 10.3945/ajcn.110.007781
Source: PubMed


Experimental and observational studies have suggested that folate may play dual roles in colorectal cancer risk depending on the timing and dose.
We examined the latency between folate intake and the incidence of colorectal cancer.
We prospectively examined associations between folate intake assessed every 2 to 4 y by using validated food-frequency questionnaires and risk of colorectal cancer and adenoma in the Nurses' Health Study and Health Professionals Follow-Up Study, which included 2299 incident colorectal cancers and 5655 colorectal adenomas from 1980 to 2004.
There was an association between total folate intake 12-16 y before diagnosis and lower risk of colorectal cancer (relative risk: 0.69; 95% CI: 0.51, 0.94; ≥800 compared with <250 μg folate/d), but there was no association between intake in the recent past and colorectal cancer risk. Long- and short-term intakes of total folate were associated with a lower risk of colorectal adenoma, with a strong association with intake 4-8 y before diagnosis (odds ratio: 0.68; 95% CI: 0.60, 0.78; ≥800 compared with <250 μg folate/d). The current use of multivitamins for >15 y, but not a shorter duration of use, was associated with lower risk of colorectal cancer; and a shorter duration of use was related to lower risk of adenoma. We did not observe an adverse effect of total folate or synthetic folic acid on risk of colorectal cancer or adenoma even during the folic acid fortification era.
Folate intake is inversely associated with risk of colorectal cancer only during early preadenoma stages.

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    • "In multivariable analyses for colorectal neoplasia, potential confounders were adjusted for by updating their values whenever new information was obtained from the follow-up questionnaires. Time-invariant variables (race, family history of colon cancer) and variables with evidence of a long induction period to affect colorectal neoplasia (calcium (Keum et al, 2014, 2015), folate (Lee et al, 2011; Keum and Giovannucci, 2014), and aspirin (Giovannucci et al, 1995; Chan et al, 2005)) were adjusted for using baseline values. Of note, as finasteride use may lie along the causal pathway between male hair patterns and colorectal neoplasia, multivariable analyses were run without and with adjustment for finasteride use. "
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    ABSTRACT: Background: Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia. Methods: From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs. Results: Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03-1.62) and 1.31 (95% CI, 1.01-1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06-1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98-1.33). Conclusions: Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia.
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    • "Cigarette smoking has been associated with increased incidence and mortality from CRC [9]. Physical activity, diet high in fruits and vegetables , fiber, resistant starch, folic acid and folate, vitamin B6 (pyridoxine), calcium and dairy products , vitamin D, magnesium, garlic, fish consumption and drugs (aspirin and NSAIDs) are protective factors against CRC [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]. "
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    • "However, this finding might also suggest that the latency time between methionine intake and the clinical detection of CRC might serve as an effect modification of the association. Recent evidence from large prospective studies documents that total folate intake in the remote past (12-16 years before diagnosis), rather than close to diagnosis (0-8 years) was associated with reduced risk of CRC; furthermore, the investigators also found that intake close to diagnosis (0-8 years) was most strongly associated with lower risk of colorectal adenoma, indicating that folate intake may be beneficial only during early preadenoma stages [33]. Both methionine and folate are the key components of one carbon metabolism. "
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