In this prospective cohort study, we found an inverse association between dietary fiber and total grain intake and cancer of the head and neck in women; inverse associations persisted across different subgroups of fiber and grains, including whole and refined grains, and did not differ by subsites. In contrast, the associations were weaker, with borderline statistical significance, in men. Our analyses suggest that the benefit conferred by higher intakes of fiber and total grains may differ by sex.
Three previous prospective studies published on dietary fiber and grain intake in relation to upper aerodigestive tract cancer, which included subsites of head and neck cancer [5
]. These studies were small (number of cases <95) and reported inconsistent results; furthermore, none comprehensively assessed fiber intake. Cohorts of Japanese [5
] and Norwegian [6
] men found inverse associations between consumption of bread and upper aerodigestive tract cancers (HR = 0.80; 95% CI = 0.41-1.56 and HR = 0.20; 95% CI = 0.1-0.5, respectively). In the Iowa Women’s Health Study, inverse associations were observed for whole grains for both oral/pharyngeal cancers (n = 53, HR = 0.47) and laryngeal cancer (n = 21, HR = 0.44), whereas total fiber consumption was inversely associated with oral/pharyngeal (HR = 0.49) but not laryngeal cancer (HR = 1.82); the authors did not conduct statistical testing due to small numbers [7
], Likewise, the epidemiological evidence from case-control studies on dietary fiber and grain intake is inconsistent [13
]. Our findings showing an inverse association between fiber intake and head and neck cancer were similar to some case-control studies [14
], but not all [35
The precise biological mechanism by which dietary fiber and grains might affect head and neck cancer risk is unknown: however, several biological reasons are plausible. Both dietary fiber and grains possess anticarcinogenic properties, which may directly or indirectly confer the protection observed. Dietary fiber scavenges nitrite, a precursor for carcinogenic nitrosoamines [36
]. Nitrosoamines are possible risk factors for head and neck cancer [4
]. Whole grains are grains in their original form contain three parts: the bran, the germ, and the endosperm [37
]. Whole grains are rich in fiber, phytochemicals, antioxidants,and phytoestrogens, and lignans [37
]. These constituents have been demonstrated to modify cancer risks, including head and neck cancer [4
]. Compared to whole grains, refined grains are nutritionally inferior because the milling process substantially reduced the nutrient contents of grains by removing the bran and germ—leaving a largely starchy endosperm. Our finding that refined grains also conferred protection against head and neck cancer does not support the hypothesis that starchy refined grains are risk factors for cancers [14
]. It may suggest that other constituents in the endosperm, perhaps residual resistant starch, may play a protective etiologic role. Refined grains are also enriched with B vitamins (riboflavin, niacin, thiamin and iron) [41
]. Nevertheless, it is speculative at best to attribute any of these constituents to the protection observed for refined grains in our study and additional research is warranted.
Our results may also be partly attributed to nutrients or micronutrients inherent in fruits and vegetables. Freedman et al previously showed that intake of fruits and vegetables was associated with a reduced risk of head and neck cancers in the same population [9
]. In additional analyses, we further adjusted for intakes of fruits, vegetables, folate, beta-carotene, and vitamin C. The observed inverse associations changed only slightly, suggesting that other dietary components found in fruits and vegetables do not fully explain the protective effect of dietary fiber and grains observed.
Alternatively, fiber and grain intake is associated with aspects of a healthy lifestyle, such as a lower propensity to smoke cigarettes and consume alcohol, lower BMI, and higher physical activity; as such unmeasured or poorly measured exposures could affect our results. Although we took great care to adjust for these confounders in our analyses, we cannot exclude the possibility of residual confounding affecting our results. In particular, cigarette smoking is a significant risk factor for head and neck cancer. Risk estimates for total fiber and total grains were attenuated in never smokers.
Despite similar reported median intakes of fiber and grains in the sex-specific quintiles, the observed sex-specific benefit merits further discussion. Head and neck cancer is considerably more common among men than women [4
]. The sex-ratios range from 3 to 10 by anatomic subsite and can further vary within particular subsites, such as the larynx [2
]. Tobacco exposure and alcohol consumption, both established risk factors for head and neck cancer, likely do not explain these differences as elevated incidence rates in men relative to women persisted in never smokers who did not drink alcohol in the NIH-AARP Diet and Health Study [26
]. The accumulating evidence led some investigators to postulate a possible role of estrogen and hormone-related factors in the etiology of head and neck cancer [43
]. Recent findings from the NIH-AARP Diet and Health Study showed that menopausal hormone therapy (MHT) was inversely associated with incident squamous cell carcinomas, which included head and neck cancer [46
]. Currently, it is unclear whether there is a role for dietary fiber and grains in hormone-related head and neck cancer, although dietary fiber and whole grains have been shown to reduce endogenous estrogen levels [47
]. In our analyses, additional adjustment for MHT and age at menopause did not affect the results.
The present study has several strengths. To our knowledge, it is the largest prospective cohort study to investigate the role of dietary fiber, grains, and their respective subtypes in relation to head and neck cancer, and first to report estimates across subsites within this group of malignancies. Furthermore, the relatively large number of head and neck cancers permitted assessment of sex-specific associations with dietary fiber and grain intake. The study benefits from a wide range of dietary fiber intake and detailed information on tobacco exposure and alcohol consumption, which allowed careful adjustment for these two important risk factors.
Limitations include the lack of information on human papillomavirus (HPV) infection, which is a risk factor for specific head and neck cancer subsites [49
]. We investigated multiple subtypes of fiber, grains, and subsites of head and neck cancer; therefore, it is possible that our results might be due to chance. Additionally, we lack information on smoking duration and passive smoke exposure, which could possibly confound the observed relation. Although our study is the largest to date to examine the role of fiber and grains in relation to head and neck cancer, we are still limited by a modest numbers of cases, particularly for subgroup analyses.
In conclusion, total fiber and grains were inversely associated with head and neck cancers in this prospective cohort study. We observed a more pronounced benefit with intake of total fiber and grains among women compared to men. Our findings suggest a role of fiber and grains in the etiology of head and neck cancer.