Table S2. Summary of Reviewed Studies on Diet and Thyroid Cancer

Table S2. Summary of reviewed studies on diet and thyroid cancer.

Reference Study design, Exposure and Outcome and Results Strengths and limitations sample size, measurement measurement years Horn-Ross Case-control Dietary iodine including Thyroid cancer Iodine Strengths et al. 2001 study of 608 supplement use cases identified Dietary iodine consumption not Controlled for confounding of cases and 558 collected through in- through a Cancer related to follicular cancer. many risk factors. Large sample controls from person structured Registry. Significantly lower nail iodine size. 1995-1998. interviews. Dietary levels in cases with follicular Limitations Women iodine intake calculated cancer than controls (P=0.02). Possibility of selection bias as between 20-74 based on the information Iodine consumption inversely cases were obtained from a years of age provided. Neutron related to papillary cancer risk cancer registry but controls residing in the activation analysis of when highest intake quintile were obtained through random- San Francisco toenail clippings to compared to lowest (OR 0.49, digit dialing. Possibility for recall Bay Area. measure iodine exposure 95%CI 0.29-0.84). This bias as the cases may recall over a 2-4 week period association was mostly information for questionnaires approximately 1 year attributable to multivitamin differently than the controls. before the clipping. pills. No significant association Possibility for misclassification of between papillary carcinoma iodine exposure information as and iodine. the measure for iodine intake Diet was not direct. Usefulness of the Papillary thyroid cancer not nail clipping biomarker is not related to fish consumption for well known. shellfish (OR 0.93, 95%CI 0.64- 1.3), saltwater fish (OR 0.96, 95%CI 0.69-1.3), fresh-water fish (OR 1.1, 95%CI 0.74-1.7) or canned tuna (OR 1.2, 95%CI 0.90-1.7). Cooked seaweed associated with decreased thyroid cancer risk (OR 0.61, 95%CI 0.44-0.84). Kolonel et Case-control Multiple risk factors Thyroid cancer Females: non-significant OR for Strengths al. 1990 study of 191 measured through cases identified thyroid cancer risk in highest Selection bias not likely as cases cases and 442 interview. Iodine intake through the iodine intake quartile compared selected from a population controls was measured through Hawaii Tumor to lowest (OR 1.6, 95%CI 0.8- based registry and controls matched on retrospective recall of Registry (mainly 3.2). Males: OR was 1.3 (0.4- selected through random age and sex diet. papillary cancer 3.7). sample of the population. from 1980- cases). Limitations 1987. Both Recall bias is possible as cases female and may recall diet information male residents differently than controls. The of Oahu, iodine intake was estimated Hawaii aged 18 based on diet and authors did years or older. not measure salt intake thus there is a possibility of misclassification of exposure information. Odds ratios were only adjusted for age and ethnicity but not any other confounding factors. Pettersson Ecological Iodine deficient and Thyroid cancer Age standardized incidence Strengths et al. 1996 study of 5,838 iodine sufficient areas incidence based rates increased significantly over Cancer registry is almost cases from defined on the basis of on data from the time for all types of thyroid complete reducing the 1958-1981 goiter prevalence. Salt Swedish Cancer cancer and in both regions. possibility of selection bias. using Swedish ionization was Registry. Incidence of papillary cancer Limitations Cancer introduced during this higher in iodine-sufficient areas There is a possibility of Registry. time taking off in 1966 than iodine-deficient areas. In misclassification of exposures when there was no both areas age standardized status as iodine-deficient areas difference in the incidence rate of papillary were defined by areas that prevalence of goiter cancer increased 2 fold. After previously had high rates of between these two adjusting for age, sex and birth goiter. Did not control for many areas. cohort risk of developing relevant confounding factors. papillary carcinoma in iodine Ecological study so population deficient area was significantly level associations cannot be reduced (RR 0.80, 95% 95%CI inferred to the individual. 0.73-0.88). Both males and females had higher risk of developing follicular cancer in iodine deficient region (M: RR 1.98, 95%CI 1.6-2.4; F: RR 1.17, 95%CI 1.04-1.32). Williams Ecological One region with high Incidence and The age-specific incidence of Strengths et al. 1977 study of 108 dietary iodine intake in histological type papillary carcinoma was five Both populations have broadly cases in Iceland and one region of of thyroid cancer times higher in Iceland than similar ethnic background and Iceland and average dietary iodine in both regions. Northeast Scotland across all standards of medical care. All 103 cases in intake in northeast groups. In Iceland papillary thyroid carcinomas were Northeast Scotland. carcinoma accounted for 71% of examined by the same two Scotland from all thyroid cancers but only 4% pathologists. 1944-1963. in northeast Scotland. In people Limitations over 65 the incidence of No statistical tests were undifferentiated carcinomas in performed. Did not control for Iceland was twice that of North confounding. Difficult to make East Scotland. comparisons between two populations as the populations can differ on many different factors not just iodine intake. Ecological study so population level associations cannot be inferred to the individual. Harach et Ecological Pre-prophylaxis period Incidence of Significant increase in papillary Strengths al. 2008 study of includes cases diagnosed thyroid cancer. carcinoma (P<0.001) and Pre and post iodination periods residents of 5 years before and 10 decrease in undifferentiated examined. the province of years after salt iodination carcinoma (P<0.2) between two Limitations Salta, (1958-1972). Post- time periods. The ratio of Did not control for confounding Argentina from prophylaxis period papillary to follicular carcinoma factors that may have changed 1958-2007. (1985-2007) increased from 1.7:1 to 3.9:1. over time such as standards of The overall incidence rates for medical care, environmental thyroid cancer showed a exposures, and pathological progressive increase (1.6/ criteria. Did not take into 100,000 in 1960 to 3.6/100,000 account 1988 WHO changes in in 2001) especially for papillary histopathology classification cancer. favoring the diagnosis of the papillary subtype at the cost to follicular carcinoma. Did not describe acquisition of incidence in detail and therefore it is not known if there is selection bias. Did not provide sample size of population. Ecological study so population level associations cannot be inferred to the individual. Bosetti et Pooled analysis Food frequency Thyroid cancer. No significant association with Strengths al. 2001 of 13 case- questionnaires for total thyroid cancer found for high Large sample size. Adjusted for control studies fish, salt water fish and total fish consumption in confounding from history of of 2497 cases shellfish consumption. comparison to low consumption thyroid disease and history of and 4337 (OR 0.88 95%CI 0.71-1.1). In the radiation. Evaluated controls from endemic goiter region OR was heterogeneity of the results studies 0.65 (0.48-0.88) and in iodine based on relation to endemic published rich areas was 1.1 (0.85-1.5). goiter areas and quality of the between 1980 For salt water fish consumption questionnaires. and 1997, from the OR was 1.1 (0.82-1.4) and Limitations US, Japan, for shellfish consumption it was Possibility for recall bias as China and 1.0 (0.80-1.3). Pattern of risk exposure information gathered Europe. consistent when data was through questionnaire. restricted to women and Exposure information collection papillary cancer. across the original studies was not homogeneous.

Memon et Case-control Structured questionnaire Thyroid cancer Protective effect found for high Strengths al. 2002 study of 313 asking information on from cancer consumption of fresh fish (OR Controlled for confounding matched cases many possible risk registry 0.5, 95%CI 0.4-0.7). Processed, variables. and controls factors including 13 information and canned or frozen fish increased Limitations from 1981- dietary items. charts from the risk of thyroid cancer (OR 2.2, Did not state what confounding 1999 and Kuwait Cancer 95%CI 1.6-3.0). No association variables were controlled for. includes Control Centre. found with total fish Possibility for selection bias as residents of consumption (OR 0.6, 95%CI 0.3- cases selected from a thyroid Kuwait during 1.0) or shellfish consumption cancer clinic and controls the data (OR 1.2, 95%CI 0.7-2.0). selected from local primary collection Increased risk found with high healthcare clinics. Possibility for period aged < consumption of chicken (Or 1.7, recall bias as exposure 70 years old. 95%CI 1.2-2.3). No association information was obtained found with the consumption of through a retrospective green vegetables (OR 0.8, 95%CI questionnaire. Performed 0.6-1.4). Increased risk of multiple statistical tests thyroid cancer with the increasing the probability of consumption of cabbage (OR getting a significant result by 1.9, 95%CI 1.1-3.3) and chance. cauliflower (OR 1.8, 95%CI 1.0- 3.2) but not with the consumption of Brussels sprouts (OR 0.7, 95%CI 0.1-4.3) or Broccoli (OR 0.9, 95%CI 0.2-3.6). Mack et Case-control In person or telephone Thyroid cancer Risk of thyroid cancer not Strengths al.2002 study of interview using a cases as related to shellfish consumption Eighty percent of eligible cases 292 cases and structured questionnaire identified (OR 0.8, 95%CI 0.3-2.4), participated in the study. 292 matched for multiple thyroid through the Los saltwater fish consumption (OR Matched controls on birth year, controls from cancer risk factors. Angeles County 0.6, 95%CI 0.3-1.3) or freshwater race and neighborhood. 1980-1983. Los population fish consumption (OR 0.6, 95%CI Adjusted for benign thyroid Angeles based registry. 0.2-1.7) in high intake group conditions and radiation as County women compared to low intake group. possible confounders. aged 15-54, Decreased risk of thyroid cancer Limitations English with consumption of turnips or Selection bias possible as speaking and rutabagas a few times a year for controls selected from white. all types of thyroid cancer (OR neighborhood and cases 0.6, 95%CI 0.3-1.0) and papillary selected from registry. Possible thyroid cancer (0.5, 95%CI 0.2- recall bias as exposure 0.9). Increased risk for papillary information was collected thyroid cancer was in those who through retrospective had more than 10 years use of interviews. Interviewers not multivitamin at least weekly (OR blinded leading to possible 2.9, 95%CI 1.2-7.4). interviewer bias. Sample sizes varied depending on question leading to lower power for some tests. Multiple statistical comparisons performed increasing the chance of getting statistically significant responses. Bosetti et Pooled analysis Food frequency Thyroid cancer. No significant association found Strengths al. 2002 of 11 case- questionnaire for total for thyroid cancer and high total Large sample size. Adjusted for control studies cruciferous and other cruciferous vegetable confounding from history of from US, Asia vegetable intake. consumption compared to low thyroid disease and history of and Europe of (OR 0.94, 95%CI 0.80-1.10). radiation. Evaluated 2241 cases and Results were similar when heterogeneity of the results 3716 controls, researchers looked at iodine rich based on relation to endemic published areas, endemic goiter areas, goiter areas and quality of the between 1980 women and papillary carcinoma. questionnaires. and 1997. For vegetables other than Limitations cruciferous inverse relationship Possibility for recall bias as found with thyroid cancer in exposure information gathered high consumption versus low through questionnaire. (OR 0.82, 95%CI 0.69-0.98) Exposure information collection across the original studies was not homogeneous. Markaki et Case-control Patients asked through a Thyroid cancer Increased consumption of pork Strengths al. 2003 study of food frequency cases from 2 of increased risk of thyroid cancer Cases and controls both selected 113 cases and questionnaire about the major (OR 1.63, 95%CI 1.13-2.35). from the same hospitals so 138 controls their average lifetime hospitals in Decreased risk for thyroid selection bas should not be an matched on consumption of each Athens, Greece. cancer with increased raw issue. Interviewers blinded to age, gender food item prior to a tomato (OR 0.92, 95%CI 0.85- case status. Controlled for and hospital diagnosis of thyroid 0.99) and lemon (OR 0.91, 95%CI confounding by matching on from 1990- cancer. 0.85-0.98) consumption. age, gender and health unit 1993 of male Significant dose response (equivalent to SES). Performed and female relationship found for fresh factor analysis which addresses patients from tomatoes (P =0.002) and pork the issues of multiple Greece. (P=0.001). Decreased risk for all comparisons. 100% response thyroid cancer found with the rate. consumption of fruits (OR 0.68, Limitations P=0.01), raw vegetables (OR Recall bias still a possibility 0.71, P=0.02) and mixed because exposure status vegetables and fruits (OR 0.73, measured through a P=0.04). Increased risk for retrospective questionnaire. Did follicular thyroid cancer found not report confidence intervals with increased consumption of for odds ratios of factor fish and cooked vegetables (OR analyses. 2.79, P=0.02). Fioretti et Case-control Interviews conducted Thyroid cancer Increased thyroid cancer risk Strengths al. 1999 study of using structured cases who were was associated with high refined Large sample size. Selection bias 339 cases and questionnaires on admitted to one cereal intake (OR 2.0, 95%CI 1.4- not likely as controls were 617 controls multiple risk factors. Diet of eight major 2.9) and low beta-carotene collected from the same general from 1986- measured through a food hospitals. intake (OR 1.4, 95%CI 1.0-1.9). population as the cases. 1992 of frequency questionnaire. Controlled for confounding from patients multiple risk factors. between the Limitations ages of 15 and Possibility for recall bias as 75 who resided dietary information gathered in Northern through interviews. Italy. Horn-Ross Case-control Multiple risk factors Thyroid cancer Reduced risk of thyroid cancer Strengths et al. 2002 study of 608 measured through in- cases identified found with high tofu Controlled for many possible cases and 558 person interviews using through the consumption (OR 0.50, 95%CI confounding factors including controls from standardized structured Greater Bay Area 0.30-0.84), moderate radiation, family history, and 1995-1998, questionnaires. Dietary Cancer Registry. consumption of soy-burgers and reproductive factors. Large includes intake measured through meat substitutes (OR 0.51, sample size. women a food frequency 95%CI 0.29-0.89) and high between the questionnaire to consumption of alfalfa sprouts ages of 20 and determine (OR 0.62, 95%CI 0.41-0.93). An Limitations 74 who were phytoestrogen intake. increased consumption of total Cases selected through a cancer residents of phytoestrogens associated with registry and controls selected the San decreased risk of thyroid cancer through random digit dialing Francisco Bay (OR 0.62, 95%CI 0.39-0.99). leading to the possibility of Area. selection bias. Possibility for misclassification of exposure status as not all dietary phytoestrogen sources measured.