Case–control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk

Abstract

Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg 213 His substitution (SULT1A1*2) affects its catalytic activity and thermostability. To study the association of SULT1A1*2 polymorphism with tobacco-related cancers (TRCs), a case -control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A1*2 showed significant risk association with UADT-MPN (odds ratio (OR) ¼ 5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A1*2 revealed contrasting risk association for UADT cancers (OR ¼ 1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR ¼ 0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR ¼ 1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR ¼ 0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens.

Very important pharmacogene summary: sulfotransferase 1A1

“…Contradicting association studies have also been published for prostate cancer [31][32][33]. A recent meta-analysis concluded that the SULT1A1*2 polymorphism was protective in genitourinary cancers, but was associated with increased upper aerodigestive tract cancers [34].…”

<i>Sulfotransferase</i> 1A1 G638A polymorphism, cigarette smoking and bladder cancer risk in Taiwan

“…We noted that the divergent genetic background and differing carcinogen exposure in various populations may explain the differing risk assessments related to the genetic polymorphisms [20][21][22]. Our study is weakened somewhat by recall bias, in that it can be difficult to recall carcinogen exposure at time points in the past, and cases are more motivated than controls to recollect past exposures.…”

Association of SULT1A1 Arg213His polymorphism with male breast cancer risk: results from a multicenter study in Italy

“…Given the ethnic differences in the impact of SULT1A1 Arg 213 His polymorphism reported in BC risks among women from different populations [13,14,16,17], further studies are needed to better define the role of SULT1A1 Arg 213 His polymorphism in MBC risk in additional populations.…”

“…Within the context, SULT1A1 catalyzes the sulfonation of estrogens to form biologically inactive estrogen sulfates, thus reducing the level of estrogens' exposure in target tissues, such as mammary tissue. The SULT1A1 Arg 213 His variant (rs9282861), is a very common functional polymorphism of the SULT1A1 gene [7] and many studies have associated it with BC in women, though with contrasting results [8][9][10][11][12][13] Recent meta-analysis studies have shown that SULT1A1 Arg 213 His variant is associated with increased risk of BC, particularly in post-menopausal women [14][15][16][17][18]. SULT1A1 Arg 213 His variant (rs9282861) consists of a G to A transition at nucleotide 638 and causes an Arginine (Arg) to Histidine (His) substitution at aminoacid 213.…”