Major depressive disorder causes significant morbidity, affecting people's ability to work, function in relationships, and engage in social activities. Moreover, major depressive disorder increases the risk of suicidal ideation, attempted suicide and death by completed suicide. There is evidence that chronic stress can cause major depressive disorder. As for genetic factors, only minor susceptibility genes have been reliably identified. The serotonin system provides a logical source of susceptibility genes for depression, because this system is the target of selective serotonin reuptake-inhibitor drugs that are effective in treating depression. The 5-hydroxytryptamine (serotonin) transporter (5-HTT) has received particular attention because it is involved in the reuptake of serotonin at brain synapses. One common polymorphic variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which affects the promoter of the 5-HTT gene, causes reduced uptake of the neurotransmitter serotonin into the presynaptic cells in the brain. The authors discussed the relationship between genetic polymorphisms and major depressive disorder, with special emphasis on the 5-HTTTLPR polymorphism. As the 5-HTTLPR polymorphism was significantly associated with an increased risk of major depressive disorder, the 5-HTT gene may be a candidate for a major depressive disorder susceptibility gene. As major depressive disorder is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for major depressive disorder. Hopefully, in the future we will be able to screen for major depressive disorder susceptibility by using specific biomarkers.

The purpose of the present review is to evaluate the effects of common risk factors for suicide by meta-analyses using data extracted from studies based on the psychological autopsy method. We focused on five common risk factors of suicide: substance-related disorders, mood disorders, adverse marital status, adverse employment status, and self-harm behaviors. A total of 24 articles were identified from MEDLINE in which the crude odds ratio (OR) could be calculated for the above five risk factors through 30 April 2007, using such search keywords as "suicide," "psychological autopsy," and "case-control study." Overall, both substance-related disorders [OR = 5.24; 95% confidence interval (CI) = 3.30-8.31] and mood disorders [OR = 13.42; 95% CI = 8.05-22.37] were strongly associated with suicidal risk. Suicidal attempt and deliberate self-harm, which can directly lead to completed suicide, have been shown to be very strongly associated with suicidal risk [OR = 16.33; 95% CI = 7.51-35.52]. Effects of social factors such as adverse marital and employment status were relatively small. As substance-related disorders and mood disorders were strongly associated with an increased risk of completed suicide, the comorbidity of these two disorders should be paid a maximum attention. The effective prevention of suicide depends on whether we can successfully incorporate these personal factors as well as social factors into an adequate multi-factorial model.

Chronic inhalation of cigarette smoke is a major risk factor for the development of lung cancer. It has been suggested that genetic susceptibility may contribute to the risk, because only a small portion of smokers develops the disease. Several polymorphisms that involve the metabolic activation or detoxification of carcinogens derived from cigarette smoke have been found to be associated with lung cancer risk. Many studies have focused on the relation between the distribution of polymorphic variants of different forms of the metabolic enzymes and lung cancer susceptibility. In this respect two groups of genetic polymorphisms of enzymes involved in xenobiotic metabolism, cytochrome P450 (CYP) and glutathione S-transferases (GSTs), have been discussed.CYP multigene superfamily consists of 10 subfamilies (CYP1-CYP10). A positive association between development of lung cancer and the mutant homozygous genotype ofCYP1A1 gene has been reported in several Japanese populations but such an association has not been observed in either Caucasians or African-Americans. The relation betweenCYP2D6 and lung cancer remains conflicting and inconclusive. Several polymorphisms have been identified at theCYP2E1 locus. No definitive link between the polymorphisms ofCYP2E1 and the risk of lung cancer has, however, been identified. The role of otherCYP2 isoforms in lung carcinogenesis has not been sufficiently investigated.GSTs form a superfamily of genes consisting of five distinct families, namedGSTA, GSTM, GSTP, GSTT andGSTS. The role ofGSTM, GSTT1 orGSTP1 polymorphism in modifying the lung cancer risk may be more limited than has been so far anticipated.Although some genetic polymorphisms discussed here have not shown significant increases/decreases in risk, individuals with differing genotypes may have different susceptibilities to lung cancer. Hopefully, in future studies it will be possible to screen for lung cancer using specific biomarkers.