cancer of bladder, adenocarcinoma of the esophagus, and stomach while significant
association was observed with cancer of gall bladder (Bagnardi et al. 2015).
As opposed to the studies which show a positive association between alcohol
consumption and cancer risk, there are also studies which reported an inverse
relationship. Studies on Hodgkin’s and non-Hodgkin’s lymphomas reported an
alcohol-induced decrease in the risk (Tramacere et al. 2012a, b) while protective
effect of moderate alcohol consumption on the risk of renal cell cancer has also been
reported. However, a European study did not report an inverse relationship between
alcohol intake and lymphoid neoplasms (Heinen et al. 2013). The possible reasons
for alcohol related decrease in the risk of lymphomas are not very evident though it
may be attributed partly to the inappropriate classification of drinkers as
non-drinkers as in the initial stages of the lymphomas, the cases either abstain
from drinking or reduce the alcohol intake significantly. Similarly, alcohol could
protect renal cells from cancer either due to its role in insulin sensitivity or diuresis
though no concrete evidence exists between fluid intake and cancer risk (Altieri et al.
2003). Some studies have established an association between alcohol and risk of
head and neck cancer. This was particularly evident in populations with a higher
alcohol intake as revealed by cohort and case-control studies (Viswanathan
and Wilson 2004). All forms of alcohol have been linked to the cancers of oral
cavity and pharynx with the association more strong for oral cavity compared to the
larynx and pharynx.
Alcohol poses less risk for laryngeal cancer compared to cigarette smoking;
however, cancer of the oral cavity has an increased incidence among those who
smoke and use alcohol (Choi and Kahyo 1991). The incidence of oral cancer may
remain high several years after stopping alcohol use (Franceschi et al. 2000).
10.3 Genetic Variations in Enzymes Involved in Metabolism
of Xenobiotics
10.3.1 Genetic Variations of Phase I Xenobiotic Metabolizing
Enzymes (XMEs)
The metabolism of Polycyclic Aromatic Hydrocarbons (PAHs), N-nitrosamines, and
aromatic amines is by a two-phase process. The first phase called as phase I involves
the activation of the carcinogen by enzymes encoded by the CYP gene superfamily.
Cytochrome P450s (CYPs) are the most important super family of phase I XMEs
which are ubiquitously distributed and found from bacteria to humans (Nelson et al.
1996). The root symbol “CYP” for human (“cyp” for mouse) denotes “cytochrome
P450.” The root symbol is followed by an Arabic numeral, designating the CYP
family (Nebert and Russell 2002). The CYP1, CYP2, and CYP3 enzymes are
primarily associated with the metabolism of exogenous compounds, whereas the
other CYPs mainly have endogenous roles. It is estimated that CYPs in families 1–3
are responsible for about 75% of all phase I metabolism of clinically used drugs
(Evans and Relling 1999). CYPs exhibiting important endogenous functions are well
10 Interactions of Environmental Risk Factors and Genetic Variations: Association. . .
217
association was observed with cancer of gall bladder (Bagnardi et al. 2015).
As opposed to the studies which show a positive association between alcohol
consumption and cancer risk, there are also studies which reported an inverse
relationship. Studies on Hodgkin’s and non-Hodgkin’s lymphomas reported an
alcohol-induced decrease in the risk (Tramacere et al. 2012a, b) while protective
effect of moderate alcohol consumption on the risk of renal cell cancer has also been
reported. However, a European study did not report an inverse relationship between
alcohol intake and lymphoid neoplasms (Heinen et al. 2013). The possible reasons
for alcohol related decrease in the risk of lymphomas are not very evident though it
may be attributed partly to the inappropriate classification of drinkers as
non-drinkers as in the initial stages of the lymphomas, the cases either abstain
from drinking or reduce the alcohol intake significantly. Similarly, alcohol could
protect renal cells from cancer either due to its role in insulin sensitivity or diuresis
though no concrete evidence exists between fluid intake and cancer risk (Altieri et al.
2003). Some studies have established an association between alcohol and risk of
head and neck cancer. This was particularly evident in populations with a higher
alcohol intake as revealed by cohort and case-control studies (Viswanathan
and Wilson 2004). All forms of alcohol have been linked to the cancers of oral
cavity and pharynx with the association more strong for oral cavity compared to the
larynx and pharynx.
Alcohol poses less risk for laryngeal cancer compared to cigarette smoking;
however, cancer of the oral cavity has an increased incidence among those who
smoke and use alcohol (Choi and Kahyo 1991). The incidence of oral cancer may
remain high several years after stopping alcohol use (Franceschi et al. 2000).
10.3 Genetic Variations in Enzymes Involved in Metabolism
of Xenobiotics
10.3.1 Genetic Variations of Phase I Xenobiotic Metabolizing
Enzymes (XMEs)
The metabolism of Polycyclic Aromatic Hydrocarbons (PAHs), N-nitrosamines, and
aromatic amines is by a two-phase process. The first phase called as phase I involves
the activation of the carcinogen by enzymes encoded by the CYP gene superfamily.
Cytochrome P450s (CYPs) are the most important super family of phase I XMEs
which are ubiquitously distributed and found from bacteria to humans (Nelson et al.
1996). The root symbol “CYP” for human (“cyp” for mouse) denotes “cytochrome
P450.” The root symbol is followed by an Arabic numeral, designating the CYP
family (Nebert and Russell 2002). The CYP1, CYP2, and CYP3 enzymes are
primarily associated with the metabolism of exogenous compounds, whereas the
other CYPs mainly have endogenous roles. It is estimated that CYPs in families 1–3
are responsible for about 75% of all phase I metabolism of clinically used drugs
(Evans and Relling 1999). CYPs exhibiting important endogenous functions are well
10 Interactions of Environmental Risk Factors and Genetic Variations: Association. . .
217