['The molecular basis of sporadic medullary thyroid carcinoma (MTC) remains elusive. While germline gain-of-function mutations in the RET proto-oncogene cause hereditary MTC, somatic activating RET mutations and loss of heterozygosity of markers in various chromosomal regions representing deletions of tumour suppressor genes, have been described in a variable number of sporadic MTC. A previous report suggested that the presence of a germline variant at RET codon 836 (S836S) was associated with the development of sporadic MTC and, furthermore, that the presence of S836S was highly correlated with somatic RET M918T mutation in the MTC. Thus, we sought to determine if the S836S variant would be associated with sporadic MTC from a completely different population base, that of Andalucia.', 'This is a case-control study to determine whether the presence of RET germline S836S is correlated with sporadic MTC in Andalucia.', 'Thirty-two patients with sporadic MTC from the Andalucia region of Spain, serviced by our University Hospital, were ascertained throughout the period 1995-99. Sporadic MTC was defined as a lack of personal or family history suggestive of multiple endocrine neoplasia type 2 (MEN 2) and lack of germline RET mutations which define any MEN 2 subtype. A region and race matched cohort of 250 controls was also obtained.', "The frequency of the S836S allele was determined in cases and controls and compared using the standard chi-squared statistic and Fisher's exact test.", "The polymorphic allele frequency at codon 836 in the control population (18/500 chromosomes, 3.6%) differed significantly from the MTC case cohort, 9.3% of case chromosomes (six of 64 alleles, Fisher's exact test, two-tailed, P = 0.043)."] Is germline sequence variant S836S in the RET proto-oncogene associated with low level predisposition to sporadic medullary thyroid carcinoma in the Spanish population?