Gene–Occupation Interactions in Lung Cancer Risk—Letter Free

Malhotra and colleagues (1) report significant gene–occupation exposure interactions involving several genes implicated in the etiology of lung cancer, including those comprising the B-cell antigen receptor pathway. B cells produce immunoglobulins (Ig), which are important players in humoral immunity to both self- and non-self antigens. IgG is the most abundant class of Ig. It is encoded by four closely linked and highly polymorphic loci on chromosome 14q32 (2). Over three decades ago, using a candidate gene approach, Nakao and colleagues (3) presented a highly significant association between Ig GM 1,2,13,15,16,21 genotype and lung cancer (χ²_1df = 10.97, P = 0.0009). Therefore, it is relevant to inquire whether any SNPs that define GM allotypes were included in the pathway analyses conducted by Malhotra and colleagues (1).

GM allotypes could be mechanistically involved in gene–occupational exposure interactions in lung cancer through the antigen processing/presenting pathway: They could act as recognition structures on B-cell membrane–bound IgG for the occupational exposure triggers and present them to the components of the T-cell activation pathway. It is noteworthy that both B-cell and T-cell antigen pathways were significantly associated with occupational exposure-associated susceptibility to lung cancer (1).