Thyroid Function and Cancer Risk: The Rotterdam Study

Abstract

Context: In vitro and in vivo experiments have assigned both oncosuppressive and oncogenic properties to thyroid hormones. Population-based studies have found inconclusive results. Objective: We aimed to prospectively assess the relation between thyroid function and incident cancer in a population-based setting. Design, Setting, and Participants: The current study is a prospective population-based cohort study including 10 318 participants for whom baseline measurements of free T4 (FT4) and/or TSH were available. Main Outcome Measures: Cox proportional hazards models were used to assess hazard ratios (HRs) of any solid non-skin cancer, as well as lung, breast, prostate, and gastrointestinal cancer specifically. Results: Higher FT4 levels were associated with a higher risk of any solid cancer (HR, 1.42; 95% confidence interval [CI], 1.12–1.79), lung cancer (HR, 2.33; 95% CI, 1.39–3.92) and breast (HR, 1.77; 95% CI, 1.10–2.84) cancer. The risk estimates were similar after exclusion of thyroid-altering medication, but the association lost significance for breast cancer. Compared with the lowest FT4 tertile, the highest tertile was associated with a 1.13-fold increased risk of any solid, 1.79-fold increased risk of lung, and 1.14-fold increased risk of breast cancer (P for trend <.05 for all). For TSH levels we found no associations with cancer risk. There was no differential effect of sex or age on the association between thyroid function and cancer risk. Conclusions: Higher FT4 levels are significantly associated with an increased risk of any solid, lung, and breast cancer. Further research should elucidate the underlying pathophysiological mechanisms.

Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study

“…A recent cohort study of 5,886 female participants found that the highest FT4 tertile of FT4 level compared to the lowest FT4 tertile was associated with 1.14-fold increased risk of breast cancer. 29 However, this association was not statistically significant after excluding thyroid-altering medication. 29 We found no significant difference between thyroid hormone levels and breast cancer development in association with menopausal status even though the associations were stronger among postmenopausal women than in premenopausal women.…”

“…That study used a hospital diagnosis of thyroid disease based on the Danish National Patient Registry and was limited by lack of laboratory data. A recent cohort study of 5,886 female participants found that the highest FT4 tertile of FT4 level compared to the lowest FT4 tertile was associated with 1.14‐fold increased risk of breast cancer . However, this association was not statistically significant after excluding thyroid‐altering medication …”

“…However, a majority of these studies were cross‐sectional and were limited by temporal ambiguity of thyroid function and breast cancer. Until now, six prospective studies have demonstrated an association between thyroid hormones and subsequent breast cancer risk, reporting conflicting results . A study by Tosovic et al of 2,696 premenopausal and postmenopausal women demonstrated that adjusted HR (95% CI) in the T3 fourth quartile compared to the first quartile was 1.87 (1.12–3.14) .…”

“…Until now, six prospective studies have demonstrated an association between thyroid hormones and subsequent breast cancer risk, reporting conflicting results. 5,7,[27][28][29][30] A study by Tosovic et al of 2,696 premenopausal and postmenopausal women demonstrated that adjusted HR (95% CI) in the T3 fourth quartile compared to the first quartile was 1.87 (1.12-3.14). 5 A later study by Tosovic et al of 680 control cases and 676 breast cancer cases also reported that FT4 level was positively associated with high breast cancer risk; multivariable-adjusted odds ratios for women with FT4 level above the median vs. below the median was 1.40 (1.10-1.77).…”

Thyroid‐associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study

“…33 In addition, the majority of prospective studies on thyroid analytes have indicated an association with BC risk, although there are still no conclusive results. 10,12,[34][35][36][37] Regarding our studied analyte fT4, our research group and another large prospective study have recently shown that high fT4 was associated with an increase in BC risk 10,37 but a smaller prospective study reported low fT4 to be related to an increased BC risk. 35 For TPO-Ab, cross-sectional studies have found a correlation between presence of TPO-Ab and BC, as reviewed by Hardefeldt et al, 32 and our previous study indicated that prediagnostic TPO-Ab positivity decreases BC risk.…”