Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2020 Mar 1.
Published in final edited form as: Eur J Cancer Prev. 2019 Mar;28(2):102–108. doi: 10.1097/CEJ.0000000000000431

Fish/Shellfish Intake and the Risk of Head and Neck Cancer

Kathleen M McClain 1, Patrick T Bradshaw 3, Nikhil K Khankari 4, Marilie D Gammon 1, Andrew F Olshan 1,2
PMCID: PMC6077110  NIHMSID: NIHMS932593  PMID: 29406335

Abstract

Fish intake and other dietary sources of omega-3 fatty acids have been shown to be associated with a reduced risk for some cancers. Although previous studies of head and neck cancer have reported associations with different dietary factors, including reduced risks for fruits and vegetables and putatively healthy dietary patterns, associations specific to fish intake are unclear. This study investigated the association between fish/shellfish intake and risk of squamous cell carcinoma of the head and neck (SCCHN) using data from the Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study conducted in 46 NC counties with cases recruited from 2002 through 2006. Controls were frequency matched to the cases on age, sex, and race; the final sample size was 1,039 cases and 1,375 controls. Demographic, lifestyle, and dietary information were collected using an in-person interviewer-administered structured questionnaire. Multivariable-adjusted ORs and 95% confidence intervals (CIs) were estimated with unconditional logistic regression. Subjects whose fish/shellfish intake was among the highest tertile had a 20% lower odds of SCCHN compared to those in the lowest tertile (OR: 0.80; 95% CI: 0.60, 1.07) after adjustment for the matching and other factors (income, energy intake, fruit intake, cigarette smoking, and alcohol intake). The inverse association was more pronounced for oral cavity and oropharyngeal tumors, for African Americans, and for females, but CIs were wide. To further investigate this potential risk reduction strategy for SCCHN, future studies should consider examining specific fish/shellfish, cooking practices, and other omega-3 fatty acid sources.

Keywords: head and neck cancer, risk factors, diet, fish, shellfish

INTRODUCTION

Head and neck cancers (HNCs) typically include cancers of the oral cavity, pharynx, and larynx. In 2016 there were an estimated 48,330 new cases of oral cavity/pharyngeal cancer and 9,570 deaths in the United States (US). Additionally, 13,430 new cases of laryngeal cancer and 3,620 deaths were expected (Siegel et al., 2016). HNCs are characterized by disparities in both sex and race: males are affected more than females, and African Americans are affected more than whites (Marur and Forastiere, 2008).

Tobacco use and alcohol intake are the most well-established risk factors for HNC (Hashibe et al., 2007,Hashibe et al., 2009,Maasland et al., 2014,Rettig and D’Souza, 2015). These factors have been shown to have dose-response relationships with HNC (Hashibe et al., 2007,Maasland et al., 2014), and there is evidence of a synergistic joint effect between them (Hashibe et al., 2009,Maasland et al., 2014). In addition, approximately 60–70% of oropharyngeal squamous cell carcinoma cases are now associated with the human papillomavirus (Chaturvedi et al., 2011) Although these risk factors may be responsible for a majority of HNC cases, other nutrition-related factors, such as body mass index (BMI) and dietary factors, have been shown to be associated with HNCs. In some studies, lower BMI has been associated with higher risk of HNC when compared to ideal BMI (18.5–24.9 kg/m2), whereas higher BMI has been associated with decreased risk of HNC (Gaudet et al., 2010,Petrick et al., 2014,Maasland et al., 2015). Research on diet has primarily focused on fruit and vegetable intake, and select micronutrients typically found in fruits/vegetables (Edefonti et al., 2015,Galeone et al., 2015,Leoncini et al., 2015), where higher intake of both fruits and vegetables has been associated with decreased risk of HNC (Chainani-Wu, 2002,Freedman et al., 2008,Lucenteforte et al., 2009).

Intake of fish and shellfish, a primary source of long-chain omega-3 polyunsaturated fatty acids, is a potentially modifiable risk factor for HNC. Omega-3 fatty acids, in particular the long-chain omega-3 fatty acids, have been shown to exhibit anti-inflammatory effects (Larsson et al., 2004), which may disrupt tumor growth and progression (Balkwill and Mantovani, 2001). In laboratory studies omega-3 fatty acids have been shown to reduce tumor formation and growth in mice (Fay et al., 1997,Rose and Connolly, 1999). The human body cannot make omega-3 fatty acids, and must rely on external sources for these essential fats; consumption of fish and other marine life is the primary external source (Rose and Connolly, 1999,Calder, 2011).

The limited evidence for the relationship between fish/shellfish consumption and HNCs has been gleaned from the analysis of dietary indices and patterns (Samoli et al., 2010,Toledo et al., 2010,Bradshaw et al., 2012,Edefonti et al., 2012,De Stefani et al., 2013,Filomeno et al., 2014,Li et al., 2014). These studies have suggested that fish/shellfish intake may reduce risk, but are considered as part of an overall “healthy” diet (plenty of fruits and vegetables, lean meats, etc.). Thus, the specific relationship of fish/shellfish consumption with HNC risk is unclear.

The objective of the study reported here was to estimate the association between fish/shellfish intake and the risk of squamous cell carcinoma of the head and neck (SCCHN). Secondary aims were to examine if these associations varied by SCCHN cancer sites, race, and sex.

METHODS

The Carolina Head and Neck Cancer Epidemiology (CHANCE) Study, a population-based case-control study of SCCHN, was conducted between 2002 and 2006 in central and eastern North Carolina (NC). The institutional review boards of participating institutions approved the study protocol. Details of the study have been published previously (Divaris et al., 2010), and are summarized below.

Study population

Cases were adults aged 20–80 with newly diagnosed first primary invasive squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx between January 1, 2002 and February 28, 2006 in a 46-county area of NC. Cases were ascertained through the NC Central Cancer Registry, which contacted the registrars of 54 area hospitals on a monthly basis to identify potentially eligible cases.

Controls were adults aged 20–80 who had never been diagnosed with HNC and were residents of the same 46-county area of NC. Potentially eligible controls were identified using the NC Department of Motor Vehicle records; and controls were frequency matched to the cases using random sampling with stratification on age group (20–49, 50–54, 55–59, 60–64, 65–69, 70–74, 75–80 years), sex (male and female), and race (white, African American, and other).

Of the eligible cases, contact was made with 98%, and 82% agreed to participate in the study; and of the eligible controls, contact was made with 80% and 61% agreed to participate.

Cases of lip cancer (due to the etiological differences), SCCHN cases with a site designation of “not otherwise specified,” and cases with proxy interviews were excluded. The final analysis sample included 1,039 cases (90% of case participants) and 1,375 controls (98% of control participants).

The subset of the CHANCE study population used here is similar to the overall CHANCE population (Divaris et al., 2010). This subset has a median age of 59 and 63 for cases and controls, respectively. It is also predominantly white (74% of cases, 80% of controls), male (78% of cases, 69% of controls), and of lower socioeconomic status (61% of cases, 45% of controls with annual household income ≤$40,000).

Previous studies conducted using the CHANCE study population have shown that former and current tobacco use was associated with increased risk of SCCHN (in both African Americans and whites, but the effect estimate was more pronounced among African Americans) (Stingone et al., 2013); increasing lifetime alcohol use (ml of ethanol) was associated with increased risk of SCCHN (more pronounced among African Americans than whites) (Stingone et al., 2013); and leanness is associated with increased risk of SCCHN in both African Americans and whites, while overweight and obesity is associated with decreased risk in African Americans only, when compared to ideal BMI (Petrick et al., 2014).

Data collection

During an in-home visit a study nurse administered a structured questionnaire, which was completed by the subject, or by a proxy if the subject was deceased. The questionnaire assessed demographic, lifestyle, oral health, and dietary information. Dietary factors were assessed using a version of the National Cancer Institute’s (NCI) Diet History Questionnaire (DHQ) (NIH, 2007), which assessed servings per day, per week, or per month of various food items one year prior. The dietary data was then processed with the Diet*Calc analysis program (Applied Research Program, 2005) to attain information on total energy intake per day (kcal/day) and intake of individual food items per day (g/day).

Exposure assessment

Fish/shellfish intake was self-reported using the DHQ described in the previous paragraph, and asked how often participants ate “fish sticks, fish, other seafood and shellfish”, where answers ranged from never, 1–6 times per year, to 2 times per day. Using the information on frequency of fish/shellfish consumption, the number of oz. per day consumed for each participant was calculated. Fish/shellfish intake was then categorized using tertiles of intake (oz/day) based on intake distribution of the controls with cutpoints of ≤0.07, 0.07–0.14, and >0.14 oz/day.

Covariate assessment

Annual household income was self-reported and categorized as follows: ≤$20,000, $20,001–$40,000, $40,001–$60,000, $60,001–$80,000, and >$80,000. Self-reported weight and height were used to calculate BMI (weight (kg)/height (m)2), which was categorized using the standard World Health Organization classifications (WHO, 1987,1995): ≤18.5 kg/m2, 18.5–24.9 kg/m2, 25.0–29.9 kg/m2, and ≥30.0 kg/m2. Cigarette smoking duration was assessed as lifetime years of smoking and categorized into never smokers, and quartiles based on the control distribution: 1–14 years, 15–27 years, 28–40 years, >40 years. Alcohol intake was assessed as lifetime consumption of ethanol (ml) and categorized into never drinkers, and tertiles based on the controls’ distribution: 1–66,268.8 ml, 66,268.8–331,344 ml, >331,344 ml. Fruit intake and vegetable intake were both modeled continuously in servings per day. Total energy intake was modeled continuously in kcal/day, centered at the standard dietary recommendation of 2,000 kcal/day (US Department of Health Human Services, 2015).

Statistical methods

Unconditional logistic regression (Hosmer Jr et al., 2013) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between fish/shellfish intake and SCCHN, and all models included terms for the matching factors of age, sex, and race. In secondary analyses we estimated site-specific associations for oral cavity, oropharyngeal, and laryngeal cancer (compared to controls) in a single model using polytomous logistic regression (Kleinbaum and Klein, 2002); heterogeneity by tumor site was evaluated using a Wald test at the 0.10 significance level (Hosmer Jr et al., 2013). Hypopharyngeal cases were excluded from this analysis due to small sample size. Effect measure modification (EMM) on the multiplicative scale was assessed for race and sex at the 0.10 significant level using the likelihood ratio test comparing models with and without the interaction term (Breslow et al., 1982,Rothman et al., 2008,Hosmer Jr et al., 2013).

Potential confounders were selected a priori using directed acyclic graph (Greenland et al., 1999) analysis and backwards elimination strategy with significance level of 0.10. Potential confounders included: annual household income, BMI, cigarette smoking duration, lifetime alcohol intake, fruit intake, vegetable intake, and total energy intake. After assessment of confounders, models were adjusted for the matching factors of age, sex, and race, as well as annual household income, duration of cigarette smoking, lifetime alcohol intake, fruit intake, and total energy intake. SAS version 9.3 (SAS Institute, Cary, NC) was used for all analyses.

RESULTS

The distribution of select participant characteristics, including BMI, smoking, alcohol intake, and energy intake, is shown by case/control status in Table 1. The mean age of controls was slightly higher than for the cases. The vast majority of participants, both cases and controls, were male and white. Controls were more likely to be college graduates or higher, compared to cases. Cases reported higher levels of both cigarette smoking and alcohol intake, and reported higher energy intakes from the FFQ. The majority of SCCHN cases were diagnosed with cancer of the larynx or oropharynx.

Table 1.

Demographic characteristic distribution by case control status among the CHANCE study participants, 2002–2006

Cases
(N=1,039)
N (%)		 Controls
(N=1,375)
N (%)
Age
  <50 yrs 196 (18.9) 156 (11.4)
  50–54.9 yrs 164 (15.8) 163 (11.9)
  55–59.9 yrs 180 (17.3) 206 (15.0)
  60–64.9 yrs 174 (16.8) 208 (15.1)
  65–69.9 yrs 141 (13.6) 246 (17.9)
  70–74.9 yrs 118 (11.4) 231 (16.8)
  ≥75 yrs 66 (6.4) 165 (12.0)
Sex
  Male 808 (77.8) 946 (68.8)
  Female 231 (22.2) 429 (31.2)
Race
  White 768 (73.9) 1,099 (79.9)
  African American 249 (24.0) 259 (18.8)
  Other 22 (2.1) 17 (1.2)
Income
  ≤$20,000 366 (36.4) 255 (19.3)
  $20,001–$40,000 251 (25.0) 335 (25.3)
  $40,001–$60,000 172 (17.1) 284 (21.4)
  $60,001–$80,000 89 (8.9) 174 (13.1)
  ≥$80,001 127 (12.6) 277 (20.9)
Education
  High School or Less 656 (63.1) 541 (39.4)
  Some College 243 (23.4) 411 (30.0)
  College Graduation or More 140 (13.5) 423 (30.8)
BMI
  <18.5 kg/m2 35 (3.4) 11 (0.8)
  18.5–24.9 kg/m2 379 (36.5) 411 (29.9)
  25.0–29.9 kg/m2 364 (35.0) 553 (40.3)
  ≥30.0 kg/m2 261 (25.1) 398 (29.0)
Cigarette Smoking Duration
  Never Smokers 118 (11.4) 525 (38.3)
  ≤14 yrs 59 (5.7) 214 (15.6)
  15–27 yrs 131 (12.6) 215 (15.7)
  28–40 yrs 347 (33.4) 209 (15.2)
  >40 yrs 383 (36.9) 209 (15.2)
Alcohol Intake (lifetime)
  Never Drinkers 96 (9.7) 292 (21.9)
  <66,268.8 ml 108 (11.0) 348 (26.1)
  66,268.8 –331,344 ml 187 (19.0) 341 (25.6)
  >331,344 ml 595 (60.3) 351 (26.4)
Total Energy Intake (kcal/day)* 2,572.3 (1,027.4) 1,970.4 (701.9)
Fruit Intake (servings/day)* 2.1 (1.7) 2.6 (1.7)
Vegetable Intake (servings/day)* 2.4 (1.4) 2.1 (1.0)
Cancer Site
  Larynx 446 (42.9) N/A
  Oral Cavity 195 (18.8) N/A
  Oropharynx 343 (33.0) N/A
  Hypopharynx 55 (5.3) N/A
Open in a new tab
*

Mean (SD)

As shown in Table 2, after adjustment for the matching factors of age, sex, and race, as well as annual household income, duration of cigarette smoking, lifetime alcohol intake, and fruit intake, the highest tertile of fish/shellfish intake compared to the lowest tertile was associated with a 20% decrease in risk of SCCHN (ORT3 vs. T1=0.80; 95% CI: 0.60, 1.07), but confidence intervals included the null value. The odds ratio was similar when adjusted only for the matching factors.

Table 2.

Association between fish/shellfish intake and SCCHN in CHANCE participants, 2002–2006

Fish/shellfish intake
(oz. per day)		 Cases
N (%)		 Controls
N (%)		 Matching only*
OR (95% CI)		 Adjusted**
OR (95% CI)
≤0.07 444 (42.7) 598 (43.5) 1 1
0.07–0.14 386 (37.2) 462 (33.6) 1.10 (0.92, 1.33) 1.13 (0.89, 1.42)
>0.14 209 (20.1) 315 (22.9) 0.83 (0.67, 1.04) 0.80 (0.60, 1.07)
Open in a new tab
*

Adjusted for matching factors of age, sex, and race

**

Adjusted for matching factors of age, sex, and race; income; smoking; drinking; total energy intake; fruit intake

For the analysis of SCCHN tumor sites (Table 3), the inverse association for the highest intake was more pronounced for oral cavity (ORT3 vs. T1=0.71; 95% CI: 0.44, 1.17) and oropharyngeal cancers (ORT3 vs. T1=0.78; 95% CI: 0.53, 1.13) than for laryngeal cancers (ORT3 vs. T1=0.92; 95% CI: 0.64, 1.33). The differences by tumor site were not statistically significant (pheterogeneity=0.86).

Table 3.

Association between fish/shellfish intake and SCCHN by cancer site*, 2002–2006

Fish/shellfish intake
(oz. per day)		 Controls
N (%)		 Larynx Oral Cavity Oropharynx
N (%) OR (95% CI)** N (%) OR (95% CI)** N (%) OR (95% CI)**
≤0.07 598 (43.5) 188 (42.2) 1 89 (45.6) 1 143 (41.7) 1
0.07–0.14 462 (33.6) 165 (37.0) 1.21 (0.90, 1.63) 70 (35.9) 1.02 (0.69, 1.51) 125 (36.4) 1.09 (0.80, 1.49)
>0.14 315 (22.9) 93 (20.9) 0.92 (0.64, 1.33) 36 (18.5) 0.71 (0.44, 1.17) 75 (21.9) 0.78 (0.53, 1.13)
pheterogeneity=0.86
Open in a new tab
*

55 hypopharynx cancer cases were not included in this analysis

**

Adjusted for: matching factors of age, sex, and race; income; smoking; drinking; total energy intake; fruit intake

With regards to race (Table 4), the decreased risk for SCCHN was more pronounced among African Americans (ORT3 vs. T1=0.66; 95% CI: 0.37, 1.16) than whites (ORT3 vs. T1=0.88; 95% CI: 0.64, 1.22), but the difference was not statistically significant on the multiplicative scale (pinteraction=0.67). The inverse association for fish/shellfish intake varied by sex (Table 4) with effect estimates more pronounced among females (ORT3 vs. T1=0.67; 95% CI: 0.38, 1.17) than among males (ORT3 vs. T1=0.85; 95% CI: 0.61, 1.17), although the difference was non-significant (pinteraction=0.72).

Table 4.

Association between fish/shellfish intake and SCCHN by race* and sex, 2002–2006

Fish/shellfish intake (oz. per day) White African American
Cases Controls OR (95% CI)** Cases Controls OR (95% CI)**
≤0.07 355 (46.2) 501 (45.6) 1 78 (31.3) 93 (35.9) 1
0.07–0.14 287 (37.4) 364 (33.1) 1.18 (0.91, 1.53) 94 (37.8) 93 (35.9) 1.02 (0.60, 1.75) pheterogeneity=0.67
>0.14 126 (16.4) 234 (21.3) 0.88 (0.64, 1.22) 77 (30.9) 73 (28.2) 0.66 (0.37, 1.16)
Fish/shellfish intake (oz. per day) Males Females
Cases Controls OR (95% CI)*** Cases Controls OR (95% CI)***
≤0.07 333 (41.2) 399 (42.2) 1 111 (48.1) 199 (46.4) 1
0.07–0.14 309 (38.2) 331 (35.0) 1.17 (0.90, 1.54) 77 (33.3) 131 (30.5) 1.01 (0.63, 1.60) pheterogeneity=0.72
>0.14 166 (20.5) 216 (22.8) 0.85 (0.61, 1.17) 43 (18.6) 99 (23.1) 0.67 (0.38, 1.17)
Open in a new tab
*

39 participants classified as “other” race were not included in this analysis

**

Adjusted for: matching factors of age and sex; income; smoking; drinking; total energy intake; fruit intake

***

Adjusted for: matching factors of age and race; income; smoking; drinking; total energy intake; fruit intake

DISCUSSION

Among this population-based sample of NC residents, higher intake of fish/shellfish was associated with a non-statistically significant 20% decrease in risk of SCCHN, which is consistent with our hypothesis of an inverse association with omega-3 food sources. The association with fish/shellfish intake may be more pronounced for cancers of the oral cavity and oropharynx, and perhaps among African Americans and females, but the precision of these comparisons are limited by sample size.

Previous epidemiologic studies examining the relationship between fish/shellfish intake and HNC are inconsistent. The INHANCE Consortium, of which CHANCE is a member, has previously shown an association between higher levels of seafood intake and lower risk of overall HNC (ORQ4 vs. Q1=0.83; 95% CI: 0.74, 0.94) with a significant linear dose-response relationship (p=0.02), but EMM by race and other factors was not considered separately for seafood (Chuang et al., 2012). Also, INHANCE included Asian populations, where seafood intake is substantially higher than it is in the U.S. (FAOU, 2014); thus our study provides estimates among a bi-racial NC population which is more generalizable to the U.S. population. In the NIH-AARP cohort, there was a slightly decreased but non-statistically significant effect between fish intake and cancer of the oral cavity (HRQ5 vs. Q1=0.90; 95% CI: 0.75, 1.09), but a null association with laryngeal cancer (HRQ5 vs. Q1=1.03; 95% CI: 0.79, 1.36 (Daniel et al., 2011). In another study conducted in Italy and Switzerland, Bravi et al. found results similar to our own, including inverse relationships with higher levels of fish intake among oral and pharyngeal cancers (ORT3 vs. T1=0.81; 95% CI: 0.60, 1.09) (Bravi et al., 2013). In another Italian study, however, Garavello et al. did not find any consistent relationship between fish and oral and pharyngeal cancer (Garavello et al., 2008). Similarly, a Spanish study found no association between fish and oral/oropharyngeal cancer (Sanchez et al., 2003). Finally, the most recent study using the Netherlands Cohort Study (Perloy et al., 2017) found no associations between fish intake and HNC overall or by cancer site. The inconsistencies between these studies and our analyses may be due to the differences in seafood intake, either differences in absolute intake, differences in type of fish/shellfish consumed (Mahaffey, 2004), or differences in cooking practices (Strobel et al., 2012) among country-specific populations, or the number of food line items specific to fish/shellfish on these FFQs.

However, studies examining a posteriori dietary patterns that include fish as a contributor or studies using a priori patterns, such as the Mediterranean diet, have shown reduced risk of HNCs with higher adherence. A study by Bradshaw et al. also using the CHANCE data found a reduction in risk (OR=0.53; 95% CI: 0.39, 0.71) for HNC with highest adherence to a “healthy” dietary pattern, which included non-fried seafood (Bradshaw et al., 2012). The estimate for oral/pharyngeal cancer was slightly more pronounced (OR=0.45; 95% CI: 0.32, 0.63), whereas the estimate for laryngeal cancer was attenuated (OR=0.73; 95% CI: 0.48, 1.10). A study from Uruguay (De Stefani et al., 2013) created a “prudent” dietary pattern in which fish was a contributor. For overall HNC in men only, this study found a 48% reduction in risk for highest adherence to the pattern (OR=0.52; 95% CI: 0.34, 0.76) (De Stefani et al., 2013). For male HNC by cancer site, the estimates were similar for oral/pharyngeal cancer and laryngeal cancer. A Brazilian study with a “prudent” dietary pattern, of which fish was a contributor, found a similar reduction in risk comparing those with the highest adherence to the lowest (OR=0.44; 95% CI: 0.25, 0.75) (Toledo et al., 2010).

In the Mediterranean diet, fish intake is a primary component for creating these diet scores (Trichopoulou et al., 2003). A Greek study examining upper aerodigestive tract cancers found a reduction in risk (OR=0.59; 95% CI: 0.39, 0.89) with a three-unit increase in Mediterranean diet score (MDS) (Samoli et al., 2010). A study from Italy and Switzerland found an OR=0.73 (95% CI: 0.68, 0.78) for every 1-unit increase in MDS for oral and pharyngeal cancer (Filomeno et al., 2014). Li et al used the NIH-AARP cohort study to examine the alternate MDS (aMDS) and HNC, and by cancer site (Li et al., 2014). For men, there was a reduction in risk for HNC (HR=0.80; 95% CI: 0.64, 1.01) comparing the highest aMDS to the lowest, and for women a more pronounced reduction (HR=0.42; 95% CI: 0.24, 0.74). In men, higher aMDS was associated with reduced risk of laryngeal (HR=0.68; 95% CI: 0.45, 1.03) and orohypopharyngeal cancers (HR=0.54; 95% CI: 0.38, 0.79). In women, an association was only seen with oral cavity cancer (HR=0.47; 95% CI: 0.24, 0.93).

These dietary pattern studies support the results from our study, however the patterns represent an overall health-conscious diet consisting of fruits, vegetables, lean proteins, etc. in addition to fish intake. Our study is examining a more distinct exposure than the pattern represented by overall intake.

A component of fish/shellfish that could be a factor in the inverse associations noted by ours and some studies is long-chain omega-3 fatty acids, specifically eicosapentaenoic and docosahexaenoic fatty acids (Rose and Connolly, 1999,Stephenson et al., 2013,Fabian et al., 2015). These long-chain omega-3 fatty acids which are found in fish have been hypothesized to reduce cancer risk (Chavarro et al., 2007,Zheng et al., 2013) through several mechanisms including suppressing mutations (Larsson et al., 2004), reducing inflammation (Larsson et al., 2004), inhibiting cell growth (Larsson et al., 2004,Stephenson et al., 2013), and enhancing apoptosis (Larsson et al., 2004,Stephenson et al., 2013). There has also been suggestion that these fatty acids may be associated with increased immune function through this enhancement of apoptosis (Troyer and Fernandes, 1996,Avula et al., 2000,Johnson, 2002). Lastly, fish intake could reduce cancer risk by replacing less healthy options (such as red meat) with fish/shellfish; which can displace intake of some pro-inflammatory omega-6 fatty acids, which are hypothesized to increase cancer risk (Rose and Connolly, 1990,Brown et al., 2006), with omega-3 fatty acids. Thus, fish/shellfish intake should be considered for further examination as a risk reduction strategy for HNC because of its high content (relative to other food items) of omega-3 fatty acids.

Our population-based study among blacks and whites included a comprehensive assessment of dietary habits, and both known and suspected risk factors for SCCHN. However, there are a few limitations to consider when interpreting our findings. There was a lower response rate among the controls as compared to the cases, but is typical of population-based studies conducted among racially diverse populations (Hall et al., 2000). Using an FFQ as the dietary assessment method, allows for the possibility of measurement error, but is reliable for ranking individuals by relative intake (Willett, 2013). Due to the retrospective nature of the study, there is the potential for recall bias. However, overall intake of fish/shellfish among our population-based biracial sample was similar to the average intake in the US (NCI). Thus, recall of fish/shellfish does not appear to be a strong concern in our study. Nonetheless, nationally only about 10% of individuals meet or exceed recommendations for seafood intake. Fish is a substantially stronger source of dietary omega-3 than is shellfish (US Department of Health Human Services, 2007), however due to the wording of the CHANCE questionnaire, we were unable to examine associations with fish separately, which would likely have increased the magnitude of the reduced effect estimates reported here. Finally, like all previous studies of SCCHN, we were not able to account for any possible omega-3 dietary supplement use.

In summary, our results suggest that higher consumption of fish/shellfish may be associated with a lower risk of SCCHN, and this association may be more pronounced for oral cavity and oropharyngeal cancer, for African Americans, and for females, although confidence intervals were wide. Our findings are consistent with some previous studies. To further investigate this potential association for SCCHN, future studies should consider examining fish and shellfish separately, specific fish/shellfish (such as white vs. dark, oily fish), cooking methods, and other omega-3 fatty acid sources including dietary supplements.

Acknowledgments

Funding: This study was supported in part by the National Cancer Institute (R01-CA90731), the National Institute of Environmental Health Sciences (P30ES10126) and National Institute of Diabetes and Digestive and Kidney Disease (P30DK56350).

References

  1. National Cancer Institute, editor. Applied Research Program. Diet*Calc Analysis Program, Version 1.4.3. Bethesda, MD: National Cancer Institute; 2005. [Google Scholar]
  2. Avula CR, Lawrence RA, Jolly CA, Fernandes G. Role of n-3 polyunsaturated fatty acids (PUFA) in autoimmunity, inflammation, carcinogenesis, and apoptosis. Recent Research Developments in Lipids. 2000;4(2):303–319. [Google Scholar]
  3. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? The Lancet. 2001;357(9255):539–545. doi: 10.1016/S0140-6736(00)04046-0. [DOI] [PubMed] [Google Scholar]
  4. Bradshaw PT, Siega-Riz AM, Campbell M, Weissler MC, Funkhouser WK, Olshan AF. Associations between dietary patterns and head and neck cancer: the Carolina head and neck cancer epidemiology study. American Journal of Epidemiology. 2012;175(12):1225–1233. doi: 10.1093/aje/kwr468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bravi F, Bosetti C, Filomeno M, Levi F, Garavello W, Galimberti S, et al. Foods, nutrients and the risk of oral and pharyngeal cancer. British Journal of Cancer. 2013;109(11):2904–2910. doi: 10.1038/bjc.2013.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Breslow N, Day N, Schlesselman JJ. Statistical Methods in Cancer Research. Volume 1-The Analysis of Case-Control Studies. Journal of Occupational and Environmental Medicine. 1982;24(4):255–257. [Google Scholar]
  7. Brown MD, Hart CA, Gazi E, Bagley S, Clarke NW. Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs. British Journal of Cancer. 2006;94(6):842–853. doi: 10.1038/sj.bjc.6603030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Calder PC. Fatty acids and inflammation: the cutting edge between food and pharma. European Journal of Pharmacology. 2011;668:S50–S58. doi: 10.1016/j.ejphar.2011.05.085. [DOI] [PubMed] [Google Scholar]
  9. Chainani-Wu N. Diet and oral, pharyngeal, and esophageal cancer. Nutrition and Cancer. 2002;44(2):104–126. doi: 10.1207/S15327914NC4402_01. [DOI] [PubMed] [Google Scholar]
  10. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. Journal of Clinical Oncology. 2011;29(32):4294–4301. doi: 10.1200/JCO.2011.36.4596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chavarro JE, Stampfer MJ, Li H, Campos H, Kurth T, Ma J. A Prospective Study of Polyunsaturated Fatty Acid Levels in Blood and Prostate Cancer Risk. Cancer Epidemiology Biomarkers & Prevention. 2007;16(7):1364–1370. doi: 10.1158/1055-9965.epi-06-1033. [DOI] [PubMed] [Google Scholar]
  12. Chuang S-C, Jenab M, Heck JE, Bosetti C, Talamini R, Matsuo K, et al. Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium. Cancer Causes & Control. 2012;23(1):69–88. doi: 10.1007/s10552-011-9857-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Daniel CR, Cross AJ, Graubard BI, Hollenbeck AR, Park Y, Sinha R. Prospective investigation of poultry and fish intake in relation to cancer risk. Cancer Prevention Research. 2011;4(11):1903–1911. doi: 10.1158/1940-6207.CAPR-11-0241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. De Stefani E, Boffetta P, Correa P, Deneo-Pellegrini H, Ronco AL, Acosta G, et al. Dietary patterns and risk of cancers of the upper aerodigestive tract: a factor analysis in Uruguay. Nutrition and Cancer. 2013;65(3):384–389. doi: 10.1080/01635581.2013.761254. [DOI] [PubMed] [Google Scholar]
  15. Divaris K, Olshan AF, Smith J, Bell ME, Weissler MC, Funkhouser WK, et al. Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study. Cancer Causes & Control : CCC. 2010;21(4):567–575. doi: 10.1007/s10552-009-9486-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Edefonti V, Hashibe M, Ambrogi F, Parpinel M, Bravi F, Talamini R, et al. Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium. Annals of Oncology. 2012;23(7):1869–1880. doi: 10.1093/annonc/mdr548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Edefonti V, Hashibe M, Parpinel M, Turati F, Serraino D, Matsuo K, et al. Natural vitamin C intake and the risk of head and neck cancer: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. International Journal of Cancer. 2015;137(2):448–462. doi: 10.1002/ijc.29388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fabian CJ, Kimler BF, Hursting SD. Omega-3 fatty acids for breast cancer prevention and survivorship. Breast Cancer Research. 2015;17(1):1. doi: 10.1186/s13058-015-0571-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fay MP, Freedman LS, Clifford CK, Midthune DN. Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review. Cancer Research. 1997;57(18):3979–3988. [PubMed] [Google Scholar]
  20. Filomeno M, Bosetti C, Garavello W, Levi F, Galeone C, Negri E, et al. The role of a Mediterranean diet on the risk of oral and pharyngeal cancer. British Journal of Cancer. 2014;111(5):981–986. doi: 10.1038/bjc.2014.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Food Agriculture Organization Of The United States Nations, FAOU. State of the World Fisheries and Aquaculture 2014. Fao; 2014. [Google Scholar]
  22. Freedman ND, Park Y, Subar AF, Hollenbeck AR, Leitzmann MF, Schatzkin A, et al. Fruit and vegetable intake and head and neck cancer risk in a large United States prospective cohort study. International Journal of Cancer Journal international du Cancer. 2008;122(10):2330–2336. doi: 10.1002/ijc.23319. [DOI] [PubMed] [Google Scholar]
  23. Galeone C, Edefonti V, Parpinel M, Leoncini E, Matsuo K, Talamini R, et al. Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium. International Journal of Cancer. 2015;136(4):904–914. doi: 10.1002/ijc.29044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Garavello W, Lucenteforte E, Bosetti C, La Vecchia C. The role of foods and nutrients on oral and pharyngeal cancer risk. Minerva Stomatologica. 2008;58(1–2):25–34. [PubMed] [Google Scholar]
  25. Gaudet MM, Olshan AF, Chuang S-C, Berthiller J, Zhang Z-F, Lissowska J, et al. Body mass index and risk of head and neck cancer in a pooled analysis of case–control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. International Journal of Epidemiology. 2010;39(4):1091–1102. doi: 10.1093/ije/dyp380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Greenland S, Pearl J, Robins JM. Causal diagrams for epidemiologic research. Epidemiology. 1999:37–48. [PubMed] [Google Scholar]
  27. Hall IJ, Newman B, Millikan RC, Moorman PG. Body Size and Breast Cancer Risk in Black Women and White Women The Carolina Breast Cancer Study. American Journal of Epidemiology. 2000;151(8):754–764. doi: 10.1093/oxfordjournals.aje.a010275. [DOI] [PubMed] [Google Scholar]
  28. Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, et al. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Journal of the National Cancer Institute. 2007;99(10):777–789. doi: 10.1093/jnci/djk179. [DOI] [PubMed] [Google Scholar]
  29. Hashibe M, Brennan P, Chuang S-c, Boccia S, Castellsague X, Chen C, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiology Biomarkers & Prevention. 2009;18(2):541–550. doi: 10.1158/1055-9965.EPI-08-0347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. US Department of Health Human Services. US Department of Agriculture. Dietary Guidelines for Americans, 2005. Washington, DC: US Government Printing Office; 2005. 2007. [Google Scholar]
  31. US Department of Health Human Services. 2015–2020 Dietary Guidelines for Americans. US Government Printing Office; Washington, DC: 2015. [Google Scholar]
  32. Hosmer DW, Jr, Lemeshow S, Sturdivant RX. Applied Logistic Regression. John Wiley & Sons; 2013. [Google Scholar]
  33. Johnson I. Anticarcinogenic effects of diet-related apoptosis in the colorectal mucosa. Food and Chemical Toxicology. 2002;40(8):1171–1178. doi: 10.1016/s0278-6915(02)00051-0. [DOI] [PubMed] [Google Scholar]
  34. Kleinbaum DG, Klein M. Polytomous logistic regression. Logistic Regression: A Self-Learning Text. 2002:267–299. [Google Scholar]
  35. Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A. Dietary long-chain n− 3 fatty acids for the prevention of cancer: a review of potential mechanisms. The American Journal of Clinical Nutrition. 2004;79(6):935–945. doi: 10.1093/ajcn/79.6.935. [DOI] [PubMed] [Google Scholar]
  36. Leoncini E, Nedovic D, Panic N, Pastorino R, Edefonti V, Boccia S. Carotenoid intake from natural sources and head and neck cancer: a systematic review and meta-analysis of epidemiological studies. Cancer Epidemiology and Prevention Biomarkers. 2015;24(7):1003–1011. doi: 10.1158/1055-9965.EPI-15-0053. [DOI] [PubMed] [Google Scholar]
  37. Li W-Q, Park Y, Wu JW, Goldstein AM, Taylor PR, Hollenbeck AR, et al. Index-based dietary patterns and risk of head and neck cancer in a large prospective study. The American Journal of Clinical Nutrition. 2014;99(3):559–566. doi: 10.3945/ajcn.113.073163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lucenteforte E, Garavello W, Bosetti C, La Vecchia C. Dietary factors and oral and pharyngeal cancer risk. Oral Oncology. 2009;45(6):461–467. doi: 10.1016/j.oraloncology.2008.09.002. [DOI] [PubMed] [Google Scholar]
  39. Maasland DH, van den Brandt PA, Kremer B, Schouten LJ. Body mass index and risk of subtypes of head-neck cancer: the Netherlands Cohort Study. Scientific Reports. 2015;5 doi: 10.1038/srep17744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Maasland DH, van den Brandt PA, Kremer B, Goldbohm RAS, Schouten LJ. Alcohol consumption, cigarette smoking and the risk of subtypes of head-neck cancer: results from the Netherlands Cohort Study. BMC Cancer. 2014;14(1):1. doi: 10.1186/1471-2407-14-187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Mahaffey KR. Fish and shellfish as dietary sources of methylmercury and the ω-3 fatty acids, eicosahexaenoic acid and docosahexaenoic acid: risks and benefits. Environmental Research. 2004;95(3):414–428. doi: 10.1016/j.envres.2004.02.006. [DOI] [PubMed] [Google Scholar]
  42. Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clinic Proceedings. 2008;83(4):489–501. doi: 10.4065/83.4.489. [DOI] [PubMed] [Google Scholar]
  43. National Cancer Institute. Usual Dietary Intakes: Food Intakes, U.S. Population, 2007–10. Epidemiology and Genomics Research Program website [Google Scholar]
  44. National Institutes of Health Applied Research Program, National Cancer Institute. Diet History Questionnaire, Version 1.0 2007 [Google Scholar]
  45. Perloy A, Maasland DH, van den Brandt PA, Kremer B, Schouten LJ. Intake of meat and fish and risk of head–neck cancer subtypes in the Netherlands Cohort Study. Cancer Causes & Control. 2017:1–10. doi: 10.1007/s10552-017-0892-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Petrick JL, Gaudet MM, Weissler MC, Funkhouser WK, Olshan AF. Body mass index and risk of head and neck cancer by race: the Carolina Head and Neck Cancer Epidemiology Study. Annals of Epidemiology. 2014;24(2):160–164. e161. doi: 10.1016/j.annepidem.2013.11.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Rettig EM, D’Souza G. Epidemiology of Head and Neck Cancer. Surgical Oncology Clinics of North America. 2015;24(3):379–396. doi: 10.1016/j.soc.2015.03.001. [DOI] [PubMed] [Google Scholar]
  48. Rose DP, Connolly JM. Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture. Cancer Research. 1990;50(22):7139–7144. [PubMed] [Google Scholar]
  49. Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacology & Therapeutics. 1999;83(3):217–244. doi: 10.1016/s0163-7258(99)00026-1. [DOI] [PubMed] [Google Scholar]
  50. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. Lippincott Williams & Wilkins; 2008. [Google Scholar]
  51. Samoli E, Lagiou A, Nikolopoulos E, Lagogiannis G, Barbouni A, Lefantzis D, et al. Mediterranean diet and upper aerodigestive tract cancer: the Greek segment of the Alcohol-Related Cancers and Genetic Susceptibility in Europe study. British Journal of Nutrition. 2010;104(09):1369–1374. doi: 10.1017/S0007114510002205. [DOI] [PubMed] [Google Scholar]
  52. Sanchez M, Martinez C, Nieto A, Castellsague X, Quintana M, Bosch F, et al. Oral and oropharyngeal cancer in Spain: influence of dietary patterns. European Journal of Cancer Prevention. 2003;12(1):49–56. doi: 10.1097/00008469-200302000-00008. [DOI] [PubMed] [Google Scholar]
  53. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: A Cancer Journal for Clinicians. 2016;66(1):7–30. doi: 10.3322/caac.21332. [DOI] [PubMed] [Google Scholar]
  54. Stephenson JA, Al-Taan O, Arshad A, al, Morgan B, Metcalfe MS, et al. The multifaceted effects of omega-3 polyunsaturated Fatty acids on the hallmarks of cancer. Journal of Lipids 2013. 2013 doi: 10.1155/2013/261247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Stingone JA, Funkhouser WK, Weissler MC, Bell ME, Olshan AF. Racial differences in the relationship between tobacco, alcohol, and squamous cell carcinoma of the head and neck. Cancer Causes & Control : CCC. 2013;24(4):649–664. doi: 10.1007/s10552-012-9999-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Strobel C, Jahreis G, Kuhnt K. Survey of n-3 and n-6 polyunsaturated fatty acids in fish and fish products. Lipids in Health and Disease. 2012;11(1):1. doi: 10.1186/1476-511X-11-144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Toledo ALAd, Koifman RJ, Koifman S, Marchioni DML. Dietary patterns and risk of oral and pharyngeal cancer: a case-control study in Rio de Janeiro, Brazil. Cadernos de Saude Publica. 2010;26(1):135–142. doi: 10.1590/s0102-311x2010000100014. [DOI] [PubMed] [Google Scholar]
  58. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. New England Journal of Medicine. 2003;348(26):2599–2608. doi: 10.1056/NEJMoa025039. [DOI] [PubMed] [Google Scholar]
  59. Troyer D, Fernandes G. Nutrition and apoptosis. Nutrition Research. 1996;16(11):1959–1987. doi: 10.1016/S0271-5317(96)00219-9. [DOI] [Google Scholar]
  60. Willett W. Nutritional Epidemiology [electronic resource] Oxford: Oxford University Press; 2013. [Google Scholar]
  61. World Health Organization. Measuring obesity—classification and description of anthropometric data. Report on a WHO consultation of the epidemiology of obesity. Warsaw 21–23 October 1987. Copenhagen: WHO; 1987. 1989. Nutrition Unit document, EUR/ICP/NUT 123. [Google Scholar]
  62. World Health Organization. Physical status: The use of and interpretation of anthropometry, Report of a WHO Expert Committee. 1995 [PubMed] [Google Scholar]
  63. Zheng J-S, Hu X-J, Zhao Y-M, Yang J, Li D. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ: British Medical Journal. 2013;346 doi: 10.1136/bmj.f3706. [DOI] [PubMed] [Google Scholar]

RESOURCES